curcumin and Spinal-Cord-Injuries

In this paper, we conducted a meta-analysis on the curcumin effect on functional recovery provided by the Basso, Beattie, Brenham (BBB) test for rats, and the Basso mouse scale (BMS) for mice after spinal cord injury (SCI) in animal models.. Data mining was performed, and the standard mean difference (SMD) between the treated and control (untreated) groups was calculated using the STATA software. Quality control and subgroup analysis were performed.. The analysis includes 24 experimental studies that showed curcumin had a strong significance in improving functional recovery after SCI (SMD = 3.38; 95% CI: 2.54-4.22;. These findings suggest that daily administration of curcumin can be an effective approach to improving functional recovery after SCI.

Topics: Animals; Curcumin; Disease Models, Animal; Mice; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries

Spinal cord injury (SCI) is an irreversible disease process with a high disability and mortality rate. After primary spinal cord injury, the secondary injury may occur in sequence, which is composed of ischemia and hypoxia, excitotoxicity, calcium overload, oxidative stress and inflammation, resulting in massive death of parenchymal cells in the injured area, followed by the formation of syringomyelia. Effectively curbing the process of secondary injury can promote nerve repair and improve functional prognosis. As the main active ingredient in turmeric, curcumin can play an important role in reducing inflammation and oxidation, protecting the neurons, and ultimately reducing spinal cord injury. This article reviews the effects of curcumin on the repair of nerve injury, with emphasis on the various mechanisms by which curcumin promotes the treatment of spinal cord injury.

Topics: Curcumin; Humans; Inflammation; Neuroprotective Agents; Oxidative Stress; Spinal Cord; Spinal Cord Injuries

Spinal cord injury (SCI) is a devastating event that often leads to permanent neurological deficits. Evidence from emerging studies has implicated oxygen-derived free radicals and high-energy oxidants as mediators of secondary SCI. Therefore, targeting these mediators using antioxidants could be beneficial for the disease. Several signaling pathways, such as the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1), have been associated with the regulation of some pathophysiological features of SCI. Curcumin is a plant medicinal agent whose diverse pharmacological properties have been extensively investigated and reported, notably its ability to curtail inflammatory damage by inhibiting the nuclear factor-κ-light-chain-enhancer of activated B cells. In this review, we analyze the role of curcumin in activating Nrf2/HO-1 and scavenging free radicals to repair SCI. With its minimal side effects, curcumin could be a potential therapy for SCI treatment.

Topics: Animals; Curcumin; Free Radical Scavengers; Heme Oxygenase-1; Humans; NF-E2-Related Factor 2; Signal Transduction; Spinal Cord Injuries

Spinal cord injury (SCI) is a serious central nervous system disorder caused by trauma that has gradually become a major challenge in clinical medical research. As an important branch of worldwide medical research, traditional Chinese medicine (TCM) is rapidly moving towards a path of reform and innovation. Therefore, this paper systematically reviews research related to existing TCM treatments for SCI, with the aims of identifying deficits and shortcomings within the field, and proposing feasible alternative prospects.. All data and conclusions in this paper were obtained from articles published by peers in relevant fields. PubMed, SciFinder, Google Scholar, Web of Science, and CNKI databases were searched for relevant articles. Results regarding TCM for SCI were identified and retrieved, then manually classified and selected for inclusion in this review.. The literature search identified a total of 652 articles regarding TCM for SCI. Twenty-eight treatments (16 active ingredients, nine herbs, and three compound prescriptions) were selected from these articles; the treatments have been used for the prevention and treatment of SCI. In general, these treatments involved antioxidative, anti-inflammatory, neuroprotective, and/or antiapoptotic effects of TCM compounds.. This paper showed that TCM treatments can serve as promising auxiliary therapies for functional recovery of patients with SCI. These findings will contribute to the development of diversified treatments for SCI.

Topics: Curcumin; Ginsenosides; Humans; Medicine, Chinese Traditional; Paclitaxel; Resveratrol; Spinal Cord Injuries

Spinal cord injury (SCI) is a severe nervous system disease with high morbidity and disability rate. Signaling pathways play a key role in the neuronal restorative mechanism following SCI. SRY-related high mobility group (HMG)-box gene 9 (SOX9) affects glial scar formation via Transforming growth factor beta (TGF-β) signaling pathway. Activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is transferred into nucleus to upregulate TGF-β-SOX9. Curcumin exhibits potent anti-inflammatory and anti-oxidant properties. Curcumin can play an important role in SCI recovery by inhibiting the expression of NF-κB and TGF-β-SOX9. Herein, we review the potential mechanism of curcumin-inhibiting SOX9 signaling pathway in SCI treatment. The inhibition of NF-κB and SOX9 signaling pathway by curcumin has the potentiality of serving as neuronal regenerative mechanism following SCI.

Topics: Animals; Curcumin; Humans; NF-kappa B; Signal Transduction; SOX9 Transcription Factor; Spinal Cord Injuries; Transforming Growth Factor beta

The purpose of this review is to discuss the possibility of the treatment of spinal cord injury (SCI) with curcumin via regulating the mTOR signaling pathway, which may provide another strong support for curcumin to be a promising medicine applied to the treatment of SCI. Curcumin is termed as a multifunctional targeting therapy drug that regulates the mTOR signaling pathway in the treatment of numerous diseases. Previous research has already revealed that mTOR signaling pathway plays a vital role in prognosis, which involves the axon regeneration and autophagy. This review discusses a potential mechanism that curcumin suppresses the activation of this pathway and ameliorates the microenvironment of axons regeneration which would provide a new way that induces autophagy appropriately.

Topics: Animals; Apoptosis; Curcumin; Humans; Molecular Targeted Therapy; Signal Transduction; Spinal Cord Injuries; TOR Serine-Threonine Kinases

Accurate. Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity.. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway.. Results showed that the EEG responses at lower levels of the independent variables were significantly high than at higher levels; except for oxygen content, the EEG responses at lower levels were considerably lower than at a higher level. It also showed that an upsurge in the physical demand increased lifting frequency and replication and caused decreasing in alpha power, theta/beta, alpha/beta, (theta + alpha)/beta, (theta + alpha)/(alpha + beta) and increasing in the theta power and the gamma power. Furthermore, several interactions among independent variables had significant effects on the EEG responses.. The EEG implementation for the investigation of neural responses to physical demands allows for the possibility of newer nontraditional and faster methods of human performance monitoring. These methods provide effective and reliable results as compared to other traditional methods. This study will safeguard the physical capabilities and possible health risks of industrial workers. And the applications of these tasks can occur in almost all working environments (factories, warehouses, airports, building sites, farms, hospitals, offices, etc.) that are at high altitudes. It can include lifting boxes at a packaging line, handling construction materials, handling patients in hospitals, and cleaning.

Topics: Action Potentials; Adolescent; Adult; Aged; Alanine Transaminase; Analgesics; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Apoptosis; Arrhythmias, Cardiac; Atrial Fibrillation; Biological Transport; Biomarkers; Blood Gas Analysis; Blood-Brain Barrier; Blotting, Western; Bone and Bones; Bone Marrow; Bone Neoplasms; Brain; Breast Neoplasms; Calcium; Carbon Tetrachloride; Cartilage, Articular; Case-Control Studies; CD59 Antigens; CDC2 Protein Kinase; Celastrus; Cell Cycle; Cell Division; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemical Fractionation; Colitis, Ulcerative; Colon; Computer Simulation; Curcumin; Cyclin B1; Cymenes; Cytokines; Dextran Sulfate; Dipeptidyl Peptidase 4; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Ectodysplasins; Electroencephalography; Endothelial Cells; Epithelial Cells; Epithelial-Mesenchymal Transition; Exosomes; Female; Flavonoids; G2 Phase; Gene Expression Regulation; Glial Cell Line-Derived Neurotrophic Factor; Heart Atria; Heart Conduction System; Heart Ventricles; HeLa Cells; Hemodynamics; Humans; Image Interpretation, Computer-Assisted; Indoles; Inflammation; Interleukin-1beta; Interleukin-6; Iridoid Glycosides; Ki-1 Antigen; Lens, Crystalline; Lifting; Liver; Liver Cirrhosis; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Microelectrodes; Middle Aged; Models, Cardiovascular; Multiparametric Magnetic Resonance Imaging; Myeloid Differentiation Factor 88; NADPH Oxidase 1; Neoplasm Grading; NF-kappa B; Osteoarthritis; Osteoblasts; Osteoclasts; Oxidative Stress; Oxygen; Patch-Clamp Techniques; PC-3 Cells; Permeability; Peroxidase; Plant Extracts; Plant Leaves; Prostate; Prostatic Neoplasms; Protective Agents; Proto-Oncogene Proteins c-akt; Psychophysics; Purpura, Thrombocytopenic, Idiopathic; Rabbits; Rats; Rats, Sprague-Dawley; Recovery of Function; Retrospective Studies; RNA, Long Noncoding; ROC Curve; Safety; Shoes; Signal Transduction; Sodium; Sonication; Spinal Cord; Spinal Cord Injuries; Syringa; Tight Junctions; Tissue Inhibitor of Metalloproteinase-1; Toll-Like Receptor 2; Transforming Growth Factor beta2; Transient Receptor Potential Channels; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Umbilical Cord; Up-Regulation; Ventricular Function; Young Adult

Spinal cord injury (SCI) is a devastating condition affecting young, healthy individuals worldwide. Existing agents have inadequate therapeutic efficacy, and some are associated with side effects. Our objective is to summarize and critically assess the neurological recovery and antioxidant effects of curcumin for treatment of SCI in rat models. PubMed, Embase, and Chinese databases were searched from their inception date to February 2014. Two reviewers independently selected animal studies that evaluated neurological recovery and antioxidant effects of curcumin, compared to placebo, in rats with SCI, extracted data, and assessed the methodological quality. A pair-wise analysis and a network meta-analysis were performed. Eight studies with adequate randomization were selected and included in the systematic review. Two studies had a higher methodological quality. Overall, curcumin appears to significantly improve neurological function, as assessed using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale (four studies, n=132; pooled mean difference [MD]=3.09; 95% confidence interval [CI], 3.40-4.45; p=0.04), in a random-effects model and decrease malondialdehyde (MDA) using a fixed-effects model (four studies, n=56; pooled MD=-1.00; 95% CI=-1.59 to -0.42; p=0.00008). Effect size, assessed using the BBB scale, increased gradually with increasing curcumin dosage. The difference between low- and high-dose curcumin using the BBB scale was statistically significant. Neurological recovery and antioxidant effects of curcumin were observed in rats with SCI despite poor study methodological quality.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Humans; Rats; Recovery of Function; Spinal Cord Injuries

Background Transplantation of extracellular vesicles (EVs) from stem cells is a feasible scheme for traumatic spinal cord injury (SCI). However, there is no relevant report about stem cells derived EVs loaded with curcumin for SCI treatment. Methods Mouse umbilical cord mesenchymal stem cells (MUMSCs) were incubated in the medium containing curcumin (20 µM) for 48 h. Extracellular vesicles (EVs) and curcumin-primed EVs (Cur-EVs) were collected by ultracentrifugation. Characterizations of EVs/Cur-EVs were analyzed by western blotting with CD9 and CD81 antibodies, transmission electron microscopy and nano-tracking analysis. Curcumin in the Cur-EVs was analyzed by high performance liquid phase chromatography at 430 nm wavelength. Immunofluorescence and in vivo imaging methods were used to confirm biocompatibility of EVs/Cur-EVs in vitro and in vivo. Mice with complete SCI were treated with EVs/Cur-EVs to compare the differences of locomotor function, inflammation, histological changes and remyelination. Results The isolated EVs and Cur-EVs from MUMSCs have good biocompatibility. Compared with the model mice, the locomotor function, inflammation and axonal regeneration of mice were significantly improved after injection of Cur-EVs/EVs. Furthermore, it is more effective for structural and functional recovery of complete SCI after the Cur-EVs treatment compared with the EVs treatment. In the lesioned regions, the macrophage polarization from M1 to M2 phenotype and axonal regeneration were significantly improved in the Cur-EVs group compared with the EVs group. Conclusions Our data suggested that EVs from MUMSCs might be a promising drug delivery vehicle of curcumin for the efficient and biocompatible treatment of severe SCI.

Topics: Animals; Curcumin; Extracellular Vesicles; Inflammation; Mesenchymal Stem Cells; Mice; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Umbilical Cord

The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1β, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/β-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Curcumin; Inflammation; Nanoparticles; Nerve Regeneration; Polymers; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries

The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration.. In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso-Beattie-Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining.. The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements.. Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Hydrogen-Ion Concentration; Inflammation; Micelles; Nanoparticles; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Temperature

Spinal cord injury (SCI) is a serious problem with a high prevalence worldwide. The weak capability of the spinal cord for regeneration in association with upregulation of inflammatory factors is two key obstacles against a full SCI repair. Curcumin is a natural substance with anti-inflammatory and neuroprotective effects. Here, we have used a combined strategy using stem cells and hybrid hydrogel scaffolds loaded with curcumin for SCI repair. Curcumin-loaded PLGA nanoparticles were prepared, characterized, and encapsulated into gelatin/alginate hydrogel scaffolds, which were then seeded by human endometrial stem cells (hEnSCs). The resulting construct was studied using in vitro and in vivo experiments on rat models. DLS, SEM, Zeta potential, and FTIR data confirmed the successful addition of curcumin to PLGA nanoparticles. SEM analyses indicated the successful addition of curcumin-loaded nanoparticles into the gelatin/alginate scaffold, as well as the adherence of the seeded EnSCs. Based on the results, the prepared constructs not only allowed the controlled release of curcumin but also could support the survival and growth of hEnSCs. Based on the results of BBB and histological experiments, the highest BBB score was related to the combined strategy, consistent with histological outcomes, in which our hEnSC-seeded gelatin/alginate scaffold containing curcumin-loaded nanoparticles led to improved structures of the white and gray matters in the SCI site, being indicative of the superior nerve fiber regeneration, compared to other studied groups. These results indicate the efficiency of the proposed method for SCI repair and broaden the scope for subsequent studies on spinal cord regeneration.

Topics: Alginates; Animals; Curcumin; Gelatin; Humans; Hydrogels; Nanoparticles; Rats; Spinal Cord Injuries; Spinal Cord Regeneration

Transplantation of curcumin-activated olfactory ensheathing cells (aOECs) improved functional recovery in spinal cord injury (SCI) rats. Nevertheless, little is known considering the underlying mechanisms. At the present study, we investigated the promotion of regeneration and functional recovery after transplantation of aOECs into rats with SCI and the possible underlying molecular mechanisms. Primary OECs were prepared from the olfactory bulb of rats, followed by treatment with 1µM CCM at 7-10 days of culture, resulting in cell activation. Concomitantly, rat SCI model was developed to evaluate the effects of transplantation of aOECs in vivo. Subsequently, microglia were isolated, stimulated with 100 ng/mL lipopolysaccharide (LPS) for 24 h to polarize to M1 phenotype and treated by aOECs conditional medium (aOECs-CM) and OECs conditional medium (OECs-CM), respectively. Changes in the expression of pro-inflammatory and anti-inflammatory phenotypic markers expression were detected using western blotting and immunofluorescence staining, respectively. Finally, a series of molecular biological experiments including knock-down of triggering receptor expressed on myeloid cells 2 (TREM2) and analysis of the level of apolipoprotein E (APOE) expression were performed to investigate the underlying mechanism of involvement of CCM-activated OECs in modulating microglia polarization, leading to neural regeneration and function recovery. CCM-activated OECs effectively attenuated deleterious inflammation by regulating microglia polarization from the pro-inflammatory (M1) to anti-inflammatory (M2) phenotype in SCI rats and facilitated functional recovery after SCI. In addition, microglial polarization to M2 elicited by aOECs-CM in LPS-induced microglia was effectively reversed when TREM2 expression was downregulated. More importantly, the in vitro findings indicated that aOECs-CM potentiating LPS-induced microglial polarization to M2 was partially mediated by the TREM2/nuclear factor kappa beta (NF-κB) signaling pathway. Besides, the expression of APOE significantly increased in CCM-treated OECs. CCM-activated OECs could alleviate inflammation after SCI by switching microglial polarization from M1 to M2, which was likely mediated by the APOE/TREM2/NF-κB pathway, and thus ameliorated neurological function. Therefore, the present finding is of paramount significance to enrich the understanding of underlying molecular mechanism of aOECs-based therapy and provide a novel the

Topics: Animals; Anti-Inflammatory Agents; Apolipoproteins E; Curcumin; Inflammation; Lipopolysaccharides; Microglia; NF-kappa B; Olfactory Mucosa; Rats; Recovery of Function; Signal Transduction; Spinal Cord; Spinal Cord Injuries

Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is thought to be a promising strategy for treating spinal cord injury (SCI). However, the low survival rate of transplanted hUC-MSCs limits their clinical application in cell replacement therapy. Curcumin can suppress inflammation after SCI; however, it remains unknown whether curcumin can modulate the survival of transplanted hUC-MSCs. In this study, to investigate whether curcumin could strengthen the therapeutic effects of hUC-MSC transplantation on SCI, we induced hUC-MSC apoptosis with TNF-α, transplanted hUC-MSC into SCI rats, and assessed the antiapoptotic effect and mechanism of curcumin. LDH release analysis and flow cytometry demonstrated that TNF-α led to hUC-MSC apoptosis and that curcumin increased the hUC-MSC survival rate in a dose-dependent manner. In addition, we showed that the phosphorylation levels of ERK1/2, JNK, and P38 were upregulated in apoptotic hUC-MSCs, while curcumin increased the phosphorylation of ERK1/2 but did not activate JNK or P38, and these effects were reversed by the p42/44 antagonist U0126. Furthermore, we found that the motor function scores and number of surviving HNA-positive cells were significantly increased after curcumin and hUC-MSC transplantation therapy 8 weeks post-SCI, while U0126 markedly attenuated these effects. These data confirmed that curcumin suppressed hUC-MSC apoptosis through the ERK1/2 signaling pathway and that combined curcumin and hUC-MSC treatment improved motor function in rats after SCI. The current research provides a strong basis for hUC-MSC replacement therapy in conjunction with curcumin in the treatment and management of SCI in humans.

Topics: Animals; Curcumin; Humans; MAP Kinase Signaling System; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Rats; Signal Transduction; Spinal Cord Injuries; Umbilical Cord

Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI.. By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs. A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI.

Topics: Animals; Anti-Inflammatory Agents; Biocompatible Materials; Curcumin; Extracellular Vesicles; Macrophages; Male; Mice; Mice, Inbred C57BL; Neuroprotection; Neuroprotective Agents; Spinal Cord Injuries

Paclitaxel (PTX) is an antineoplastic agent commonly used in the treatment of solid tumors and is known to cause dose-limiting peripheral neurotoxicity. This study was performed to evaluate the protective effect of curcumin (CUR) against PTX-induced spinal cord and sciatic nerve injuries in rats. The rats were administered PTX (2 mg/kg, BW) intraperitoneally for the first 5 consecutive days followed by administration of CUR (100 and 200 mg/kg, BW daily in corn oil) orally for 10 days. Our results showed that CUR significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-6, iNOS and GFAP whereas caused an increase in levels of Nrf2, HO-1 and NQO1 in the spinal cord and sciatic nerve of PTX-induced rats. In addition, CUR suppressed the activation of apoptotic and autophagic pathways by increasing Bcl-2 and Bcl-xL, and decreasing p53, caspase-3, Apaf-1, LC3A, LC3B and beclin-1 mRNA expression levels. The results showed that CUR also maintained the spinal cord and sciatic nerve histological architecture and integrity by both LFB staining and H&E staining. Immunohistochemical expressions of 8-OHdG, caspase-3 and LC3B in the PTX-induced spinal cord tissue were decreased after administration of CUR. Taken together, our findings demonstrated that CUR has protective effects on PTX-induced spinal cord and sciatic nerve injuries in rats.

Topics: Animals; Apoptosis; Autophagy; Curcumin; Inflammation; Male; Neuroprotective Agents; Paclitaxel; Rats, Sprague-Dawley; Sciatic Nerve; Sciatic Neuropathy; Spinal Cord; Spinal Cord Injuries

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal-curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.

Topics: Acetals; Animals; Cells, Cultured; Curcumin; Female; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nanoconjugates; Neural Stem Cells; Neuroprotective Agents; Polymers; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries

Virtually every person with a spinal cord injury (SCI) suffers from a neurogenic lower urinary tract dysfunction (NLUTD). In the long term, about 15% of persons with SCI depend on indwelling (suprapubic or transurethral) catheters for bladder management. About 50% of these patients suffer from catheter encrustation and blockage, which may become a vital threat for persons with SCI, as it can lead to septicemia or autonomic dysreflexia. Until today, no prophylaxis of catheter encrustations with an evidence-based proof of efficacy exists.. The homeopathic remedy Hydrastis, made from the goldenseal root, is used for the treatment of thick, mucous urine sediment. In four patients with tetraplegia (three female, one male) who managed NLUTD by suprapubic catheters, recurrent encrustations and catheter blockage occurred despite irrigation and medical treatment. Surgical urinary diversion was envisioned. Applying Hydrastis C30 once weekly as a long-term medication, in three of the four patients, catheter obstructions ceased, with a follow-up for at least 1 year. One patient is awaiting ileal conduit surgery.. According to the results of our case series, the application of Hydrastis seems to be beneficial in the prevention of encrustations of indwelling catheters in patients with SCI. As the treatment was effective and well tolerated, the problem is frequent, and effective solutions are scarce, a prospective trial seems justified.

Topics: Catheters, Indwelling; Female; Humans; Hydrastis; Male; Prospective Studies; Spinal Cord Injuries; Urinary Bladder, Neurogenic

The pro-regeneration capabilities of olfactory ensheathing cells (OECs) remain controversial. However, little is known regarding whether the transplantation of activated OECs by curcumin (CCM) elicits neural regeneration and functional recovery after spinal cord injury (SCI) in rats, and the possible molecular mechanisms have never been investigated.. Primary OECs were treated with 1μM CCM for 1-3 days. Concomitantly, activated OECs were transplanted into the traumatic spinal cord of Sprague Dawley rats. One to 9 weeks after surgery, the assessment of behavior recovery was made using the Basso, Beattie and Bresnahan (BBB) locomotor scale; electrophysiology tests, such as somatosensory evoked potential (SEP) and motor evoked potential (MEP); and the cylinder test. Pathological study, including hematoxylin and eosin staining and immunofluorescence staining for neurofilaments (NFs), was conducted at 5 weeks post-surgery. In addition, activation profiles of OECs by CCM stimulus were assessed and levels of transglutaminase-2 (TG2) and phosphatidylserine receptor (PSR) in OECs stimulated by CCM were further determined.. CCM remarkably enhanced OEC proliferation, improved cell viability and strengthened secretion of neurotrophins and anti-inflammatory factors. In addition, the levels of TG2 and PSR in CCM-treated OECs were significantly elevated. More importantly, beyond 1 week post-transplantation of CCM-treated OECs into lesioned spinal cord, BBB score and cylinder test score were significantly higher than that seen in the other three groups and a more postponed latent SEP and MEP period was noted. Furthermore, 5 weeks later, numerous, well-arranged NF-positive nerve fibers, lesions with less cavities and reduced levels of pro-inflammatory cytokines were found in activated OEC implantation groups. In addition, the number of NF-positive fibers was significantly improved and the number and area of both cavities and gliotic scars were remarkably decreased compared with the corresponding controls.. Transplantation of OECs activated by CCM promotes neural regeneration and functional recovery following SCI, the underlying mechanisms of which are intimately associated with the elevated production of neurotrophic factors and anti-inflammatory factors in OECs stimulated by CCM as well as reduced pro-inflammatory cytokines from the post-contusion spinal cord. In addition, OECs activated by CCM were mediated through TG2 and PSR.

Topics: Animals; Cell Transplantation; Cells, Cultured; Curcumin; Evoked Potentials, Motor; Evoked Potentials, Somatosensory; Nerve Regeneration; Olfactory Bulb; Protein Glutamine gamma Glutamyltransferase 2; Rats, Sprague-Dawley; Receptors, Cell Surface; Recovery of Function; Spinal Cord; Spinal Cord Injuries; Transglutaminases

Curcumin has anti-inflammatory and antioxidant activities.. This study aimed to investigate the effects of curcumin on the histological changes and functional recovery following spinal cord injury (SCI).. One hundred twenty-eight Sprague-Dawley rats were distributed into a sham, SCI only, SCI-hyperglycemia, and SCI-hyperglycemia-curcumin (200 mg/kg/day, i.p.) groups.. SCI was induced using a clip at T9-10 and hyperglycemia was induced by streptozotocin (60-70 mg/kg, i.v.). Plasma malondialdehyde levels and superoxide dismutase activity was measured to determine oxidative stress. The activity of macrophages in the spinal cord after SCI was stained by the anti-CD68 antibody (ED-1). The tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 levels were measured by enzyme-linked immunosorbent assay and Western blot was used to verify the levels of mitogen-activated protein kinases and STAT3. The glial fibrillary acidic protein expression was evaluated by immunofluorescence analysis. Functional recovery was assessed according to the Basso, Beattie, and Bresnahan scale and histologic outcome was evaluated by the lesion volume and spared tissue area.. Superoxide dismutase activity increased, the malondialdehyde level decreased, and ED-1 macrophage marker level decreased in the SCI-hyperglycemia-curcumin group than in the SCI-hyperglycemia group at 2 weeks after SCI (p<.01). The SCI-hyperglycemia-curcumin group showed a statistically significant reduction in IL-6, IL-8, and TNF-α levels compared with the SCI-hyperglycemia group after SCI. The phosphorylated-extracellular signal-regulated kinase, phosphorylated-JNK, and phospho-p38 levels were significantly lower in the SCI-hypoglycemia-curcumin group than in the SCI-hypoglycemia group. The SCI-hyperglycemia-curcumin group showed a decrease in glial fibrillary acidic protein expression after SCI compared with the SCI-hyperglycemia group. The SCI-hyperglycemia-curcumin group showed a lower lesion volume, higher spared tissue, and better functional recovery than the SCI-hyperglycemia group.. Curcumin may have a potential neuroprotective effect in SCI with hyperglycemia.. Curcumin decreased the inflammatory response and decreased astrogliosis and improved the functional recovery and histologic outcomes in SCI with hyperglycemia.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Glial Fibrillary Acidic Protein; Hyperglycemia; Interleukin-6; Male; Malondialdehyde; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries; Tumor Necrosis Factor-alpha

BACKGROUND Microglia reside in the spinal cord plays a key role in the onset, progression of post-spinal cord injury (SCI) neuroinflammation. Curcumin has been shown to exhibit diverse anti-inflammatory and anti-tumor activities. The aim of this study was to explore the effect of curcumin on the inflammatory response in lipopolysaccharide (LPS)-activated microglia and its mechanism. MATERIAL AND METHODS The expression levels of phosphorylated-p65 (p-p65), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß, and IkappaB kinase ß (IKKß) were examined by western blot assay. MiR-199b-5p expression was detected by quantitative real-time polymerase chain reaction assay. The putative binding sites of miR-199b-5p in IKKß 3'UTR were predicted by bioinformatics, and direct interaction between miR-199b-5p and IKKß was verified by dual-luciferase reporter assay and RNA-immunoprecipitation assay. RESULTS Curcumin significantly suppressed inflammatory response induced by LPS by inactivation of nuclear factor kappa B (NF-kappaB) in microglial cells, as reflected by the decreased levels of p-p65, as well as the pro-inflammatory mediators, including inducible nitric oxide synthase (iNOS), TNF-alpha, and IL-1ß. Moreover, curcumin increased the level of miR-199b-5p and decreased IKKß expression in activated microglial cells. Knockdown of miR-199b-5p or overexpression of IKKß reversed the inhibitory effect of curcumin on inflammatory response and NF-kappaB activation. MiR-199b-5p directly targeted IKKß and suppressed its expression. Silencing of IKKß abolished miR-199b-5p-stimulated inflammatory cytokines production and NF-kappaB activation. CONCLUSIONS Curcumin attenuated neuroinflammation induced by LPS through regulating miR-199b-5p/IKKß/NF-kappaB axis in microglia.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; I-kappa B Kinase; I-kappa B Proteins; Inflammation; Interleukin-1beta; Lipopolysaccharides; Mice; Microglia; MicroRNAs; Neuroimmunomodulation; NF-kappa B; NF-kappaB-Inducing Kinase; Nitric Oxide Synthase Type II; Protein Serine-Threonine Kinases; Signal Transduction; Spinal Cord Injuries; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Spinal cord injury (SCI) is a condition that puts the patient's life at risk in the acute phase and, during the chronic stage, results in permanent deficits in motor, sensory and autonomic functions. Isolated therapeutic strategies have not shown an effect on this condition. Therefore, this study aimed to evaluate the effects of electroacupuncture (EA) and curcumin, alone or combined, on the oxidative balance, motor function recovery and amount of preserved tissue following a traumatic SCI. Long-Evans rats were divided into five groups: SHAM, SCI, SCI + EA, SCI + Curcumin, and SCI + EA + Curcumin. Nitric oxide was significantly decreased in the Curcumin group; the EA, Curcumin and SCI + EA + Curcumin groups had significantly decreased hydroxyl radical and lipid peroxidation levels. Motor function recovery and the amount of preserved spinal cord tissue were significantly greater in the EA, Curcumin and EA + Curcumin groups. The results show that EA and Curcumin treatment alone or in combination decreased oxidative stress, improved functional motor recovery and increased the amount of preserved spinal cord tissue following a traumatic injury.

Topics: Animals; Curcumin; Disease Models, Animal; Electroacupuncture; Female; Lipid Peroxidation; Oxidative Stress; Rats, Long-Evans; Recovery of Function; Spinal Cord; Spinal Cord Injuries

A highly water soluble, nano-formulated curcumin was used for the treatment of the experimental model of spinal cord injury (SCI) in rats. Nanocurcumin and a vehicle nanocarrier as a control, were delivered both locally, immediately after the spinal cord injury, and intraperitoneally during the 4 consecutive weeks after SCI. The efficacy of the treatment was assessed using behavioral tests, which were performed during the experiment, weekly for 9 weeks. The behavioral tests (BBB, flat beam test, rotarod, motoRater) revealed a significant improvement in the nanocurcumin treated group, compared to the nanocarrier control. An immunohistochemical analysis of the spinal cord tissue was performed at the end of the experiment and this proved a significant preservation of the white matter tissue, a reduced area of glial scaring and a higher amount of newly sprouted axons in the nanocurcumin treated group. The expression of endogenous genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, Nfkβ) and interleukins (IL-1β, TNF-α, IL-6, IL-12, CCL-5, IL-11, IL-10, IL-13) was evaluated by qPCR and showed changes in the expression of the inflammatory cytokines in the first two weeks after SCI.

Topics: Animals; Cicatrix; Curcumin; Drug Compounding; Inflammation Mediators; Male; Nanoparticles; Neuroglia; Rats; Rats, Wistar; Spinal Cord Injuries; White Matter

In addition to imperiling an individual's daily life, spinal cord injury (SCI), a catastrophic medical damage, can permanently impair an individual's body function. Methylprednisolone (MP), a medically accepted therapeutic drug for SCI, is highly controversial for the lack of consensus on its true therapeutic effect. In recent years, curcumin has served as a potential and novel therapeutic drug in SCI. Our study was intended to investigate the precise effect of MP and curcumin in SCI. We examined the function of MP and curcumin in a SCI model rat, both in vivo and in vitro, and found that there was a momentous improvement in Basso-Beattie-Bresnahan scores in the MP-treated group when compared with Cur-treated group within 14 days. Results obtained from the histological, immunohistochemistry and ultrastructural examinations evidenced the curative effect of MP was better than curcumin before Day 14. Nonetheless, there was a significant variation in the treatment effect between the MP-treated and Cur-treated groups after 14 days. The curcumin's effectiveness was more obvious than MP after 14 days following SCI. As such, we surmise that curcumin has a better therapeutic potential than MP with a prolong treatment time in the wake of SCI. Anat Rec, 301:686-696, 2018. © 2017 Wiley Periodicals, Inc.

Topics: Animals; Curcumin; Male; Methylprednisolone; Motor Activity; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries

Spinal cord injury leads to a robust inflammatory response that is an unfavorable environment for stem cell implantation. In this study, we evaluated the effect of combined therapy of curcumin and mesenchymal stem cells (MSC) on behavioral recovery and tissue sparing, glial scar formation, axonal sprouting and inflammatory responses in a rat experimental model of spinal cord injury (SCI). Balloon-induced compression lesion was performed at thoracic (Th8-9) spinal level. Out of the four groups studied, two groups received curcumin on the surface of the spinal cord immediately after SCI and then once a week for 3 weeks together with an intraperitoneal daily curcumin injection for 28 days. The other two groups received saline. Seven days after SCI, human MSC were intrathecally implanted in one curcumin and one saline group. Both curcumin and curcumin combined with MSC treatment improved locomotor ability in comparison to the saline treated animals. The combined treatment group showed additional improvement in advanced locomotor performance. The combined therapy facilitated axonal sprouting, and modulated expression of pro-regenerative factors and inflammatory responses, when compared to saline and single treatments. These results demonstrate that preconditioning with curcumin, prior to the MSC implantation could have a synergic effect in the treatment of experimental SCI.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Disease Models, Animal; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nerve Regeneration; Rats, Wistar; Recovery of Function; Spinal Cord Injuries

Traumatic spinal cord injury (SCI) is damage to the spinal cord that results in damaged spinal cord function. As a natural compound, curcumin has recently been shown to have anti-inflammatory and strong antioxidant activities. To investigate the effect of curcumin against acute spinal cord injury (SCI), we explored its induced effects in SCI mice. Transforming growth factor (TGF)-activated kinase 1 (TAK1) is a member of the MAPKKK family and plays an essential role in TNF, IL-1, and Toll-like receptor (TLR) signaling pathways.. One hundred adult female KM mice were randomly divided into 5 groups (Control, Model, Test-L, Test-M, and Test-H). SCI was induced using the method described by Allen's. Motor function of the hindlimbs was evaluated on days 1, 7, 14, 21, and 28 after the injury using the motor rating test on the Basso mouse scale (BMS). 7 days after SCI, the levels of TNF-α, IL-1β, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA); the level of NO was evaluated by Griess assay; and Western blot was used to verify the levels of proteins in the TAK1 pathway. Expressions of GFAP positive cells in injured spinal cord were detected by immunohistochemical staining.. The experiment showed that curcumin markedly inhibited SCI-induced production of inflammatory mediators, including TNF-α, IL-1β, IL-6 (ELISA assay) and nitrite oxide (Griess method) in a concentration-dependent manner. Curcumin decreased the phosphorylation levels of TGF-β-activated kinase 1 (TAK1) protein, leading to decreased phosphorylation levels of MKK6 and p38 MAPKs, key players in the microglia-mediated inflammatory response. Curcumin also significantly down-regulated the expression levels of the NF-κB upstream regulators IκB and IκB kinase (IKK). Additionally, behavior research showed that curcumin-treated mice showed significantly improved functional recovery compared to untreated mice (BMS assay). The expressions of GFAP increased in the injured spinal cord segments, which were decreased by Teat-M and Teat-H at 7d after SCI.. Curcumin restores mice hind-limb function that has been reduced by SCI. This occurs by inhibition of TAK1/MKK6/p38MAPK via the TAK1 and NFκB pathways and inflammation. These results suggest the therapeutic potential for curcumin in the treatment of SCI.

Topics: Animals; Curcumin; Female; Gene Expression Regulation; Inflammation; MAP Kinase Kinase Kinases; Mice; Spinal Cord Injuries

To investigate the effects of curcumin on motor function, and to explore the neuroprotective mechanism of curcumin after the spinal cord injury in rats. The study will theoretical and experimental evidence for curcumin's clinical treatment.. HI-0400 spinal cord impactor was used to prepare animal models of acute of spinal cord injury. One hundred and five clean and healthy rats were randomly divide into three groups:sham operation group (Sham) spinal cord injury group (SCI) and curcumin group (SCI+CUR). Intragastric administration was administrated after 30min of the spinal cord injury model, after 1 time a day, until the death. SCI+CUR group was intragastric administration with curcumin (100 mg/kg) of 0.5% carboxymethyl cellulose sodium, and Sham and SCI group were treated with the same dose of 0.5% carboxymethyl cellulose sodium. The motor function recovery of 3,7,14,21 and 28 days after spinal cord injury were evaluated by basso,beatlie,bresnahan (BBB) score. The spinal cord tissue and blood samples were collected at postoperative 12 h, 1 d, 3 d and 7 d respectively, NF-kappa B was detected by immunofluorescence, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry. The expression of Bcl-2 and Bax was detected by Elisa.. The statistic difference of BBB score between SCI group and CUR group in 3 day was not statistically significant. It was found that the 7,14,21 and 28 days BBB score in CUR group were statistically significant higher than that in SCI group(. Curcumin can promote the recovery of hindlimb motor function after spinal cord injury in rats.The mechanism is through inhibition of NF-K B to prevent inflammation; And inhibition the expression of Bax and Caspase-3, and promotion the expression of Bcl-2 to prevent apoptosis, so as to accelerate the recovery of motor function in the rats after spinal cord injury.

Topics: Animals; Apoptosis; Curcumin; Inflammation; Random Allocation; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. Animal models of acute SCI have provided evidence that transplantation of ependymal stem/progenitor cells of the spinal cord (epSPCs) induces functional recovery, while systemic administration of the anti-inflammatory curcumin provides neuroprotection. However, functional recovery from chronic stage SCI requires additional enhancements in available therapeutic strategies. Herein, we report on a combination treatment for SCI using epSPCs and a pH-responsive polymer-curcumin conjugate. The incorporation of curcumin in a pH-responsive polymeric carrier mainchain, a polyacetal (PA), enhances blood bioavailability, stability, and provides a means for highly localized delivery. We find that PA-curcumin enhances neuroprotection, increases axonal growth, and can improve functional recovery in acute SCI. However, when combined with epSPCs, PA-curcumin also enhances functional recovery in a rodent model of chronic SCI. This suggests that combination therapy may be an exciting new therapeutic option for the treatment of chronic SCI in humans.

Topics: Acetals; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Curcumin; Delayed-Action Preparations; Female; Neuroprotective Agents; Polymers; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries; Stem Cell Transplantation

Spinal cord injury (SCI) leads to glial scar formation by astrocytes, which severely hinders neural regeneration. Curcumin (cur) can inhibit glial scar formation, but the underlying mechanism is not fully understood. Using both in vivo and in vitro experiments, the current study investigated the phenotypic transformation of astrocytes following cur and siRNA intervention during the processes of inflammation and fibrosis and determined details of the relationship between cur treatment and the glial scar components GFAP and CSPG. We found that cur and NF-κb p65 siRNA could inhibit astrocyte activation through suppressing NF-κb signaling pathway, which led to down-regulate the expression of chemokines MCP-1, RANTES and CXCL10 released by astrocytes and decreased macrophage and T-cell infiltration, thus reducing the inflammation in the glial scar. In addition, silencing SOX-9 may reduce the deposition of extracellular matrix CSPG; whereas its over-expression could increase the CSPG expression. Cur suppressedSOX-9-inducedCSPG deposition, reduced α-SMA (an important symbol of fibrosis) expression in astrocytes, altered astrocyte phenotype, and inhibited glial scar formation by regulating fibrosis. This study confirmed that cur could regulate both the NF-κb and SOX9 signaling pathways and reduce the expression of intracellular and extracellular glial scar components through dual-target regulating both inflammation and fibrosis after SCI in the rat. This study provides an important hypothesis centered on the dual inhibition of intracellular and extracellular glial scar components as a treatment strategy for SCI.

Topics: Actins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Astrocytes; Cicatrix; Curcumin; Disease Models, Animal; Extracellular Matrix; Female; Fibrosis; Inflammation; Macrophages; Random Allocation; Rats, Sprague-Dawley; RNA, Small Interfering; SOX9 Transcription Factor; Spinal Cord Injuries; T-Lymphocytes; Transcription Factor RelA

Curcumin, a polyphenolic compound extracted from the plant turmeric, has protective effects on spinal cord injury (SCI) through attenuation of inflammatory response. This study was designed to detect whether curcumin modulates toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) inflammatory signaling pathway in the injured rat spinal cord following SCI.. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. There were three groups: (a) sham group; (b) SCI group; and (g) SCI + curcumin group. We measured TLR4 gene and protein expression by real-time polymerase chain reaction and western blot analysis; NF-κB activity by electrophoretic mobility shift assay, inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels by enzyme-linked immunosorbent assay, hindlimb locomotion function by Basso, Beattie, and Bresnahan rating, spinal cord edema by wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis.. The results showed that SCI induced the up-regulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat spinal cord. Treatment with curcumin following SCI markedly down-regulated the levels of these agents related to the TLR4/NF-κB inflammatory signaling pathway. Administration of curcumin also significantly ameliorated SCI induced hind limb locomotion deficits, spinal cord edema, and apoptosis.. Post-SCI curcumin administration attenuates the TLR4/NF-κB inflammatory signaling pathway in the injured spinal cord, and this may be a mechanism whereby curcumin improves the outcome following SCI.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Curcumin; Locomotion; Male; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord Injuries; Toll-Like Receptor 4; Up-Regulation

Spinal cord injury (SCI) is characterized by a high rate of disability and imposes a heavy burden on society and patients. SCI can activate glial cells and lead to swelling, hyperplasty, and reactive gliosis, which can severely reduce the space for nerve growth. Glial cells can secrete a large amount of extracellular inhibitory components, thus altering the microenvironment of axon growth. Both these factors seriously impede nerve regeneration. In the present study, we investigate whether curcumin (cur), a phytochemical compound with potent anti-inflammatory effect, plays a role in the repair of SCI.. We established a rat model of SCI and treated the animals with different concentrations of cur. Using behavioral assessment, immunohistochemistry, real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay, we detected the intracellular and extracellular components of glial scar and related cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor (NF)-κb, transforming growth factor (TGF)-β1, TGF-β2, and sex determining region Y-box (SOX)-9.. We found that cur inhibited the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and NF-κb; reduced the expression of the intracellular components glial fibrillary acidic protein through anti-inflammation; and suppressed the reactive gliosis. Also, cur inhibited the generation of TGF-β1, TGF-β2, and SOX-9; decreased the deposition of chondroitin sulfate proteoglycan by inhibiting the transforming growth factors and transcription factor; and improved the microenvironment for nerve growth. Through the joint inhibition of the intracellular and extracellular components of glial scar, cur significantly reduced glial scar volume and improved the Basso, Beattie, and Bresnahan locomotor rating and axon growth.. Our data support a role for curcumin in promoting neural function recovery after SCI by the joint inhibition of the intracellular and extracellular components of glial scar, providing an important strategy for treating SCI.

Topics: Animals; Antineoplastic Agents; Chondroitin Sulfates; Cicatrix; Curcumin; Cytokines; Extracellular Matrix; Female; Glial Fibrillary Acidic Protein; Gliosis; Locomotion; Phytotherapy; Plant Extracts; Random Allocation; Rats, Sprague-Dawley; Spinal Cord Injuries; Transcription Factors

This work aimed to investigate the therapeutic effect of curcumin on sublesional bone loss induced by spinal cord injury (SCI) in rats. SCI model in this work was generated in rats by surgical transaction of the cord at the T10-12 level. After the surgery, animals were treated with curcumin (110 mg/kg body mass/day, via oral gavages) for 2 weeks. Treatment of SCI rats with curcumin prevented the reduction of bone mass in tibiae and femurs, preserved bone microstructure including trabecular bone volume fraction, trabecular number, and trabecular thickness in proximal tibiae, and preserved mechanical properties of femoral midshaft. Treatment of SCI rats with curcumin increased osteoblast surface and reduced osteoclast surface in proximal tibiae. Treatment of SCI rats with curcumin increased osteocalcin mRNA expression and reduced mRNA levels of tartrate-resistant acid phosphatase and mRNA ratio of receptor activator of NF-κB ligand/osteoprotegerin in distal femurs. Treatment of SCI rats with curcumin reduced serum and femoral levels of thiobarbituric acid reactive substances. Treatment of SCI rats with curcumin had no significant effect on serum 25(OH)D, but enhanced mRNA and protein expression of vitamin D receptor (VDR) in distal femurs. Treatment of SCI rats with curcumin enhanced mRNA levels of Wnt3a, Lrp5, and ctnnb1 and upregulated protein expression of β-catenin in distal femurs. In conclusions, treatment with curcumin abated oxidative stress, activated VDR, and enhanced Wnt/β-catenin pathway, which might explain its beneficial effect against sublesional bone loss following SCI in rats, at least in part.

Topics: Animals; Anti-Inflammatory Agents; Biomechanical Phenomena; Bone Density; Bone Resorption; Curcumin; Disease Models, Animal; Femur; Male; Osteoclasts; Oxidative Stress; Rats, Sprague-Dawley; Spinal Cord Injuries; Thiobarbituric Acid Reactive Substances; Tibia; Vitamin D

CISD2 is known to have roles in calcium metabolism, anti-apoptosis, and longevity. However, whether CISD2 is involved in the inflammatory response associated with injuries of the central nervous system (CNS) remains unclear. This issue is particularly relevant for traumatic spinal cord injuries (SCIs), which lack therapeutic targeting and often cause long-term disability in patients. The authors previously demonstrated the neuroprotective effects of curcumin against RANTES-mediated neuroinflammation. In this study, we investigated (1) the role of CISD2 in injury-induced inflammation and (2) whether curcumin influences CISD2 expression in acute SCI.. The efficacy of curcumin treatment (40 mg/kg i.p.) was evaluated in an animal model of SCI. In a neural cell culture model, lipopolysaccharide (LPS) was administrated to induce inflammation with the aim of mimicking the situation commonly encountered in SCI. Additionally, knockdown of CISD2 expression by siRNA (siCISD2) in LPS-challenged neural cells was performed to verify the causal relationship between CISD2 and SCI-related inflammation.. The injuries were shown to reduce CISD2 mRNA and protein expression in vivo, and CISD2-positive cells were upregulated by the curcumin treatment. LPS led to a decrease in CISD2 expression in vitro; however, treatment with 1 μM curcumin attenuated the downregulation of CISD2. Furthermore, in a cellular model of LPS-induced injury, the loss of CISD2 function caused by siCISD2 resulted in a pronounced iNOS increase as well as a decrease in BCL2 expression.. To the best of our knowledge, this is the first study to report the following: (1) CISD2 exerts anti-apoptotic and anti-inflammatory effects in neural cells; and (2) curcumin can attenuate the downregulation of CISD2 in SCI and LPS-treated astrocytes.

Topics: Animals; Astrocytes; Autophagy-Related Proteins; Carrier Proteins; Curcumin; Disease Models, Animal; Inflammation; Male; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Neuroprotective Agents; Nitric Oxide; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord Injuries

Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9-T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Disease Models, Animal; Immunomodulation; Male; Rats; Rats, Wistar; Recovery of Function; Spinal Cord; Spinal Cord Injuries

Spinal cord injury (SCI) is a serious clinical situation without any effective therapy to date. Traumatic SCI triggers a complex pathological process including inflammatory response and glial scar formation. In this study, we demonstrated that curcumin, a natural product which functions as an anti-inflammatory agent, inhibited the activation of signal transducer and activator of transcription-3 and NF-kappa B in the injured spinal cord. Curcumin treatment greatly reduced the astrogliosis in SCI mice and significantly decreased the expression of IL-1β and NO, as well as the number of Iba1(+) inflammatory cells at the lesion site. Notably, more residual axons and neurons were protected and significantly improved functional recovery was observed in the curcumin-treated mice, compared to the mice without curcumin treatment. These findings indicate that curcumin promotes spinal cord repair through inhibiting glial scar formation and inflammation and suggests the therapeutic potential of curcumin for SCI.

Topics: Animals; Cicatrix; Curcumin; Female; Gliosis; Inflammation; Interleukin-1beta; Mice, Inbred BALB C; Neuroglia; Neurons; Neuroprotective Agents; NF-kappa B; Nitric Oxide; Spinal Cord; Spinal Cord Injuries; STAT3 Transcription Factor

Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play an important role in protection against spinal cord injury (SCI) induced inflammatory response. The objective of this study was to test whether curcumin, a novel Nrf2 activator, can protect the spinal cord against SCI-induced inflammatory damage.. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. The spinal cords spanning the injury site about 0.8 cm were collected for testing. There were three groups: (a) sham group; (b) SCI group; and (c) SCI + curcumin group. We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by electrophoretic mobility shift assay, concentrations of tumor necrosis factor-α, interleukin-1β and interleukin-6 by enzyme-linked immunosorbent assay, hindlimb locomotion function by Basso, Beattie, and Bresnahan rating, spinal cord edema by the wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis.. Induction of the Nrf2 activity by curcumin markedly decreased NF-κB activation and inflammatory cytokines production in the injured spinal cord. Administration of curcumin also significantly ameliorated the secondary spinal cord damage, as shown by decreased severity of locomotion deficit, spinal cord edema, and apoptosis.. Post-SCI curcumin administration attenuates the inflammatory response in the injured spinal cord, and this may be a mechanism whereby curcumin improves the outcome following SCI.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Curcumin; Cytokines; DNA; Locomotion; Male; NF-E2-Related Factor 2; NF-kappa B; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries

The purpose of this study was investigating the effects of curcumin on the histological changes and functional recovery following spinal cord injury (SCI) in a rat model. Following either sham operation or SCI, 36 male Sprague-Dawley rats were distributed into three groups: sham group, curcumin-treated group, and vehicle-injected group. Locomotor function was assessed according to the Basso, Beattie, and Bresnahan (BBB) scale in rats who had received daily intraperitoneal injections of 200 mg/kg curcumin or an equivalent volume of vehicle for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation. BBB scores were significantly higher in rats receiving curcumin than receiving vehicle (P < 0.05). The cavity volume was significantly reduced in the curcumin group as compared to the control group (P = 0.039). Superoxide dismutase (SOD) activity was significantly elevated in the curcumin group as compared to the vehicle group but was not significantly different from the sham group (P < 0.05, P > 0.05, respectively) at one and two weeks after SCI. Malondialdehyde (MDA) levels were significantly elevated in the vehicle group as compared to the sham group (P < 0.05 at 1 and 2 weeks). MDA activity was significantly reduced in the curcumin group at 2 weeks after SCI when compared to the vehicle group (P = 0.004). The numbers of macrophage were significantly decreased in the curcumin group (P = 0.001). This study demonstrated that curcumin enhances early functional recovery after SCI by diminishing cavitation volume, anti-inflammatory reactions, and antioxidant activity.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Drug Evaluation, Preclinical; Injections, Intraperitoneal; Lipid Peroxidation; Locomotion; Male; Malondialdehyde; Neuroprotective Agents; Phytotherapy; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Superoxide Dismutase

The present study aimed to investigate the effects of curcumin on the levels of spinal cord labile zinc (Zn) and inflammatory cytokines in rats after traumatic spinal cord injury (SCI).. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. There were three groups: (a) sham group; (b) SCI group; and (c) SCI + curcumin group. We measured spinal labile Zn by N-(6-methoxy-8-quinolinyl)-4-methylbenzenesulfonamide (TSQ) fluorescence staining, inflammatory cytokines such as interleukin 1β, interleukin-6, and tumor necrosis factor α by enzyme-linked immunosorbent assay, hindlimb locomotion function by Basso, Beattie, and Bresnahan rating, spinal cord edema by wet dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis.. The results showed that SCI caused a significant increase in labile Zn and inflammatory cytokines in the injured rat spinal cord. Treatment with curcumin after SCI markedly downregulated the levels of these agents and ameliorated SCI-induced hindlimb locomotion deficits, spinal cord edema, and apoptosis.. Curcumin treatment attenuates the increase of labile Zn and the expression of inflammatory cytokines in the injured spinal cord, and this may be a mechanism whereby curcumin improves the outcome after SCI.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Curcumin; Cytokines; Disease Models, Animal; Interleukin-1beta; Interleukin-6; Locomotion; Male; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries; Tumor Necrosis Factor-alpha; Zinc

Among Spinal Cord Injury (SCI) intervention the administration of high-dose high-potency steroidal drugs such as methylprednisolone or dexamethasone is used to reduce the inflammation associated with primary injury and prevention of the subsequent secondary injury. The administration of steroids has several side-effects that jeopardize their use and therefore safer chemical neuro-entities are required. Natural compounds such as curcumin (anti-oxidant) and quercetin (anti-inflammatory) have been investigated as alternative neuroactive, but are not as potent as the steroids. Hence, they are required in very high doses which may lead to significant toxicity causing an increase in cellular levels of reactive oxygen species, active iron chelation, inhibiting the activity of the cytochrome P450 enzymes such as glutathione-S-transferase and UDP-glucuronosyltransferase. A reduction in the dose of these neuroactives is possible with the administration of a 'chemically-variant' permutation with additive or synergistic therapeutic benefits. Therefore, we hypothesize that curcumin and quercetin, both natural polyphenolic flavonoids, can "additively and synergistically" improve the physiological outcome after traumatic SCI when used in combination and termed 'Cur(Que)min' - thereby decreasing the dose levels and hence reducing the inherent high dose-cytotoxicity of the individual neuroactives. This hypothesis provides the first-account of a curcumin-quercetin combination for SCI intervention theorizing the possible biomolecular-mechanism that may provide the scientific community with a novel neuroprotective and neurotherapeutic treatment option for SCI.

Topics: Antioxidants; Curcumin; Glutathione Transferase; Humans; Inflammation; Models, Theoretical; Neuroprotective Agents; Phenol; Quercetin; Reactive Oxygen Species; Spinal Cord Injuries; Steroids

Acute traumatic spinal cord injury (SCI) is marked by the enhanced production of local cytokines and pro-inflammatory substances that induce gliosis and prevent reinnervation. The transplantation of stem cells is a promising treatment strategy for SCI. In order to facilitate functional recovery, we employed stem cell therapy alone or in combination with curcumin, a naturally-occurring anti-inflammatory component of turmeric (Curcuma longa), which potently inhibits NF-κB. Spinal cord contusion following laminectomy (T9-10) was performed using a weight drop apparatus (10 g over a 12.5 or 25 mm distance, representing moderate or severe SCI, respectively) in Sprague-Dawley rats. Neural stem cells (NSC) were isolated from subventricular zone (SVZ) and transplanted at the site of injury with or without curcumin treatment. Functional recovery was assessed by BBB score and body weight gain measured up to 6 weeks following SCI. At the conclusion of the study, the mass of soleus muscle was correlated with BBB score and body weight. Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI. Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass. These findings demonstrate that curcumin in conjunction with stem cell therapy synergistically improves recovery from severe SCI. Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.

Topics: Animals; Body Weight; Cell Proliferation; Curcumin; Female; Muscle, Skeletal; Neural Stem Cells; Organ Size; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries; Stem Cell Transplantation

Faced with the complex medical challenge presented by spinal cord injuries (SCI) and considering the lack of any available curative therapy, the development of a novel method of delivering existing drugs or candidate agents can be perceived to be as important as the development of new therapeutic molecules. By combining three ingredients currently in clinical use or undergoing testing, we have designed a central nervous system targeted delivery system based on apamin-modified polymeric micelles (APM). Apamin, one of the major components of honey bee venom, serves as the targeting moiety, poly(ethylene glycol) (PEG) distearoylphosphatidylethanolamine (DSPE) serves as the drug-loaded material, and curcumin is used as the therapeutic agent. Apamin was conjugated with NHS (N-hydroxysuccinimide)-PEG-DSPE in a site-specific manner, and APM were prepared by a thin-film hydration method. A formulation comprising 0.5 mol % targeting ligand with 50 nm particle size showed strong targeting efficiency in vivo and was evaluated in pharmacodynamic assays. A 7-day treatment by daily intravenous administration of low doses of APM (corresponding to 5 mg/kg of curcumin) was performed. Significantly enhanced recovery and prolonged survival was found in the SCI mouse model, as compared to sham-treated groups, with no apparent toxicity. A single dose of apamin-conjugated polymers was about 700-fold lower than the LD50 amount, suggesting that APM and apamin have potential for clinical applications as spinal cord targeting ligand for delivery of agents in treatment of diseases of the central nervous system.

Topics: Animals; Apamin; Chemistry, Pharmaceutical; Curcumin; Drug Carriers; Drug Delivery Systems; Mice; Micelles; Particle Size; Phosphatidylethanolamines; Polyethylene Glycols; Polymers; Spinal Cord Injuries; Succinimides

Curcumin, a yellow pigment extracted from Carcuma longa, has been demonstrated to have extensive pharmacological activity in various studies, and it exhibits protective effects on injuries involving a number of human organs. The present study was designed to evaluate the potential effect and underlying mechanism of curcumin on the motor function and spinal cord edema in a rat acute spinal cord injury (SCI) model. The SCI model was induced by a heavy object falling. At 30min after the SCI was successfully induced, the animals were intraperitoneally given 40mg/kg curcumin. The Basso, Beattie and Bresnahan scores showed that curcumin moderately improved the recovery of the motor function in the injured rats, and hematoxylin-eosin staining demonstrated the role of this compound in reducing the hemorrhage, edema and neutrophil infiltration of the traumatic spinal cord. Furthermore, curcumin also inhibited the SCI-associated aquaporin - 4 (AQP4) overexpression and glial fibrillary acidic protein (GFAP) and repressed the unusual activation of the JAK/STAT signaling pathway. In conclusion, our data demonstrate that curcumin exhibits a moderately protective effect on spinal cord injury, and this effect might be related to the inhibition of overexpressed AQP4 and GFAP and the activated JAK/STAT signaling pathway. Curcumin may have potential for use as a therapeutic option for spinal cord injuries.

Topics: Animals; Aquaporin 4; Curcumin; Disease Models, Animal; Edema; Glial Fibrillary Acidic Protein; Janus Kinases; Male; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord Injuries; STAT Transcription Factors

To investigate the effect of curcumin on calcitionin gene related peptide (CGRP) expression after spinal cord injury (SCI) in rats.. A total of 200 rats, weighing 250-300 g, were randomly divided into 4 groups (n = 50): sham-operation group, normal saline (NS) group, low-dose curcumin group (30 mg/kg), and high-dose curcumin group (100 mg/kg). In sham-operation group, only vertebral lamina excision was performed without SCI; the SCI model was established in the other 3 groups. At immediate after modeling, 30 mg/kg and 100 mg/kg curcumin were injected intraperitoneally in 2 curcumin groups, equivalent NS was given in NS group (30 mg/kg), but no treatment in sham-operation group. At 1, 3, 7, 14, and 21 days after operation, the motor neural function was evaluated by the inclined plane test and Basso-Beattie-Bresnahan (BBB) scores; immunohistochemical staining and Western blot assay were used to observe CGRP expression.. BBB score and inclined plane test score of NS group, low-dose curcumin group, and high-dose curcumin group were significantly lower than those of sham-operation group at each time point (P < 0.05). BBB score of low-dose curcumin group and high-dose curcumin group was significantly higher than that of NS group at 3, 7, 14, and 21 days after SCI (P < 0.05), and the score of high-dose group was significantly higher than that of low-dose curcumin group at 7, 14, and 21 days after SCI (P < 0.05). Inclined plane test score of low-dose curcumin group and high-dose curcumin group was significantly higher than that of NS group at 7, 14, and 21 days after SCI (P < 0.05), and the score of high-dose curcumin group was significantly higher than that of low-dose curcumin group at 7, 14, and 21 days after SCI (P < 0.05). Immunohistochemical staining results showed that the CGRP positive cells of sham-operation group was significantly more than those of the other 3 groups, and the CGRP positive cells of high-dose curcumin group were significantly more than those of low-dose curcumin group at each time point (P < 0.05); the CGRP positive cells of low- and high-dose curcumin groups were significantly more than those of NS group at 3, 7, 14, and 21 days after SCI (P < 0.05). Western blot assay results showed that the CGRP protein expressed at each time point after SCI in sham-operation group; the CGRP protein expression gradually decrease with time passing in NS group; but the CGRP protein expression gradually increased with time passing in low- and high-dose curcumin groups, and reached the peak at 14 days, then maintained a high level.. After SCI in rats, 30 mg/kg curcumin can improve rats' motor function, and 100 mg/kg curcumin effect is more obvious, especially in promoting the expression of CGRP. That may be the mechanism of protection of the nervous system.

Topics: Animals; Blotting, Western; Calcitonin Gene-Related Peptide; Curcuma; Curcumin; Disease Models, Animal; Female; Immunohistochemistry; Motor Activity; Neurons; Neuroprotective Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries; Time Factors

Spinal cord injury (SCI) is a debilitating disease. Primary SCI results from direct injury to the spinal cord, whereas secondary injury is a side effect from subsequent edema and ischemia followed by activation of proinflammatory cytokines. These cytokines activate the prosurvival molecule nuclear factor-κB and generate obstacles in spinal cord reinnervation due to gliosis. Curcumin longa is an active compound found in turmeric, which acts as an antiinflammatory agent primarily by inhibiting nuclear factor-κB. Here, the authors study the effect of curcumin on SCI recovery.. Fourteen female Sprague-Dawley rats underwent T9-10 laminectomy and spinal cord contusion using a weight-drop apparatus. Within 30 minutes after contusion and weekly thereafter, curcumin (60 mg/kg/ml body weight in dimethyl sulfoxide) or dimethyl sulfoxide (1 ml/kg body weight) was administered via percutaneous epidural injection at the injury site. Spinal cord injury recovery was assessed weekly by scoring hindlimb motor function. Animals were killed 6 weeks postcontusion for histopathological analysis of spinal cords and soleus muscle weight evaluation.. Curcumin-treated rats had improved motor function compared with controls starting from Week 1. Body weight gain significantly improved, correlating with improved Basso-Beattie-Bresnahan scores. Soleus muscle weight was greater in curcumin-treated rats than controls. Histopathological analysis validated these results with increased neural element mass with less gliosis at the contusion site in curcumin-treated rats than controls.. Epidural administration of curcumin resulted in improved recovery from SCI. This occurred with no adverse effects noted in experimental animals. Therefore, curcumin treatment may translate into a novel therapy for humans with SCI.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Contusions; Curcumin; Disease Models, Animal; Female; Hindlimb; Laminectomy; Motor Activity; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries; Thoracic Vertebrae

After acute spinal cord injury (SCI), a large number of axons are lost by a cascade of pathophysiological events known as a secondary injury. The main aim of the current study was to investigate the potential neuroprotective effects of curcumin on lipid peroxidation (LPO), neurological function, and ultrastructural findings after SCI.. Forty adult Wistar albino rats were randomized into five groups: control, SCI alone (50 g/cm weight drop), methylprednisolone sodium succinate (MPSS) (30 mg/kg), curcumin + dimethyl sulfoxide (DMSO) (300 mg/kg), and DMSO alone (0.1 mg/kg).. Administration of curcumin significantly decreased LPO in first 24 hours. However, there were no differences in the neurological scores of injured rats between the medication groups and the control group. Curcumin was more effective than DMSO and MPSS in reducing LPO, whereas DMSO was more effective than curcumin and MPSS in minimizing ultrastuctural changes. The results of this study indicate that curcumin exerts a beneficial effect by decreasing LPO and may reduce tissue damage.. Since ultrastructural and neurological findings does not support biochemical finding, our findings do not exclude the possibility that curcumin has a protective effect on the spinal cord ultrastructure and neurological recovery after SCI. A combination of curcumin with other vehicle may also have a considerable synergy in protecting spinal cord.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Female; Lipid Peroxidation; Malondialdehyde; Methylprednisolone Hemisuccinate; Mitochondria; Nerve Fibers, Myelinated; Neuroprotective Agents; Rats; Rats, Wistar; Recovery of Function; Spinal Cord; Spinal Cord Injuries

Given that the spinal cord is capable of learning sensorimotor tasks and that dietary interventions can influence learning involving supraspinal centers, we asked whether the presence of omega-3 fatty acid docosahexaenoic acid (DHA) and the curry spice curcumin (Cur) by themselves or in combination with voluntary exercise could affect spinal cord learning in adult spinal mice. Using an instrumental learning paradigm to assess spinal learning we observed that mice fed a diet containing DHA/Cur performed better in the spinal learning paradigm than mice fed a diet deficient in DHA/Cur. The enhanced performance was accompanied by increases in the mRNA levels of molecular markers of learning, i.e., BDNF, CREB, CaMKII, and syntaxin 3. Concurrent exposure to exercise was complementary to the dietary treatment effects on spinal learning. The diet containing DHA/Cur resulted in higher levels of DHA and lower levels of omega-6 fatty acid arachidonic acid (AA) in the spinal cord than the diet deficient in DHA/Cur. The level of spinal learning was inversely related to the ratio of AA:DHA. These results emphasize the capacity of select dietary factors and exercise to foster spinal cord learning. Given the non-invasiveness and safety of the modulation of diet and exercise, these interventions should be considered in light of their potential to enhance relearning of sensorimotor tasks during rehabilitative training paradigms after a spinal cord injury.

Topics: Animals; Arachidonic Acid; Brain-Derived Neurotrophic Factor; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Curcumin; Cyclic AMP Response Element-Binding Protein; Diet; Docosahexaenoic Acids; Fatty Acids; Learning; Male; Mice; Physical Conditioning, Animal; Psychomotor Performance; Qa-SNARE Proteins; Spinal Cord; Spinal Cord Injuries

The pathogenesis of cervical spondylotic myelopathy (CSM) is related to both primary mechanical and secondary biological injury. The authors of this study explored a novel, noninvasive method of promoting neuroprotection in myelopathy by using curcumin to minimize oxidative cellular injury and the capacity of omega-3 fatty acids to support membrane structure and improve neurotransmission.. An animal model of CSM was created using a nonresorbable expandable polymer placed in the thoracic epidural space, which induced delayed myelopathy. Animals that underwent placement of the expandable polymer were exposed to either a diet rich in docosahexaenoic acid and curcumin (DHA-Cur) or a standard Western diet (WD). Twenty-seven animals underwent serial gait testing, and spinal cord molecular assessments were performed after the 6-week study period.. At the conclusion of the study period, gait analysis revealed significantly worse function in the WD group than in the DHA-Cur group. Levels of brain-derived neurotrophic factor (BDNF), syntaxin-3, and 4-hydroxynonenal (4-HNE) were measured in the thoracic region affected by compression and lumbar enlargement. Results showed that BDNF levels in the DHA-Cur group were not significantly different from those in the intact animals but were significantly greater than in the WD group. Significantly higher lumbar enlargement syntaxin-3 in the DHA-Cur animals combined with a reduction in lipid peroxidation (4-HNE) indicated a possible healing effect on the plasma membrane.. Data in this study demonstrated that DHA-Cur can promote spinal cord neuroprotection and neutralize the clinical and biochemical effects of myelopathy.

Topics: Aldehydes; Animals; Brain-Derived Neurotrophic Factor; Chronic Disease; Curcuma; Diet; Disease Models, Animal; Docosahexaenoic Acids; Male; Neuroprotective Agents; Qa-SNARE Proteins; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

Traumatic spinal cord injury (SCI) is a major cause of long-term disability. However, therapeutic agents targeting SCI are sorely lacking. The aim of this study was to investigate whether curcumin has neuroprotective effects after SCI in rats.. Studies were performed in 39 male Sprague-Dawley rats after spinal cord hemisection. The animals were randomly divided into three groups: sham, vehicle, and curcumin. The Basso, Beattie, and Bresnahan (BBB) scale was used to evaluate functional outcome. Specimens were tested for histologic, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), and immunohistochemical staining. Primary cultured astrocytes were used to test the inhibitory effect of curcumin on glial reactivation.. The BBB scores for the affected hindlimb after hemisection were significantly improved in the curcumin-treated group compared with the vehicle group (on d 3 and 7; P < 0.001). Immunohistochemistry of NeuN revealed remarkable neuronal loss in the vehicle group after hemisection. In comparison, curcumin significantly protected neurons after SCI (curcumin compared with vehicle; P < 0.001). Furthermore, curcumin significantly attenuated apoptosis after SCI (curcumin compared with vehicle; P < 0.001). RT-PCR demonstrated that the expression of glial fibrillary acidic protein (GFAP) was significantly inhibited by curcumin.. Curcumin inhibited apoptosis and neuron loss, quenched astrocyte activation, and significantly improved neurologic deficit 7 d after spinal cord hemisection. By down-regulating GFAP expression, curcumin seems to attenuate astrocyte reactivation, which may be beneficial for neuronal survival. This is the first report demonstrating the successful treatment of SCI by curcumin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Astrocytes; Cells, Cultured; Curcumin; Disease Models, Animal; Glial Fibrillary Acidic Protein; In Situ Nick-End Labeling; Male; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

This experimental study was performed to investigate the benefit of curcumin via its antioxidant effect on spinal cord injury (SCI) in rats.. Twenty-four adult Wistar albino rats were randomized into three groups. SCI was performed by the weight-drop model. Group 1 underwent laminectomy followed by SCI and received no medication. Group 2 underwent laminectomy followed by SCI and received curcumin (200 mg/kg/day orally). Group 3 underwent laminectomy followed by SCI and received methylprednisolone (30 mg/kg intraperitoneally). Twenty-four hours later, blood samples were obtained from all rats; serum superoxide dismutase (SOD) and malondialdehyde (MDA) levels were determined, and the obtained results were compared.. SOD level in the curcumin group was higher than in the control group (p < 0.000) and methylprednisolone group (p < 0.012). MDA level in the curcumin group was lower than in the control group (p < 0.042). Similarly, the MDA level in the methylprednisolone group was lower than in the control group (p < 0.001).. The results of the present study show that curcumin effectively protects the spinal cord tissues against oxidative damage.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Curcumin; Disease Models, Animal; Laminectomy; Male; Malondialdehyde; Methylprednisolone; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Spinal Cord Injuries; Superoxide Dismutase

Curcumin has been proposed for treatment of various neuroinflammatory and neurodegenerative conditions, including post-traumatic inflammation during acute spinal cord injury (SCI). In this study, we examined whether curcumin anti-inflammation involves regulation of astrocyte reactivation, with special focus on the injury-induced RANTES (regulated on expression normal T-cell expressed and secreted) from astrocytes in acute SCI. Male Sprague-Dawley (SD) rats were subjected to impact injury of the spinal cord followed by treatment with curcumin (40 mg/kg i.p.). RANTES and inducible nitric oxide synthase expression as well as RANTES-positive astrocytes were all induced by injury accompanied by the elevation of lipid peroxidation, and attenuated by the curcumin treatment. In primary cultured rat astrocytes challenged with lipopolysaccharide (LPS) to mimic astrocyte reactivation following SCI, LPS induces robust increase of RANTES expression and the effect was also reduced by 1 μM curcumin treatment. Furthermore, cortical neurons cultured with astrocyte conditioned medium (ACM) conditioned with both LPS and curcumin (LPS-curcumin/ACM), which characteristically exhibited decreased RANTES expression when compared with ACM from astrocytes treated with LPS alone (LPS/ACM), showed higher level of cell viability and lower level of cell death as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity assay and lactate dehydrogenase release assay, respectively. Knockdown of RANTES expression by siRNA (siRANTES) shows reduced RANTES expression and release from LPS-reactivated astrocytes, and ACM obtained from this condition (LPS-siRANTES/ACM) becomes less cytotoxic as compared with the LPS-ACM. Therefore, curcumin reduction of robust RANTES production in reactivated astrocytes both in vitro and in vivo may contribute to its neuroprotection and potential application in SCI.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Astrocytes; Cells, Cultured; Chemokine CCL5; Coculture Techniques; Curcumin; Disease Models, Animal; Gliosis; Lipopolysaccharides; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

Curcumin is a polyphenol extracted from the rhizome of Curcuma longa and well known as a multifunctional drug with anti-oxidative, anticancerous, and anti-inflammatory activities. The aim of the study was to evaluate and compare the effects of the use of the curcumin and the methylprednisolone sodium succinate (MPSS) functionally, biochemically, and pathologically after experimental spinal cord injury (SCI).. Forty rats were randomly allocated into five groups. Group 1 was performed only laminectomy. Group 2 was introduced 70-g closing force aneurysm clip injury. Group 3 was given 30 mg/kg MPSS intraperitoneally immediately after the trauma. Group 4 was given 200 mg/kg of curcumin immediately after the trauma. Group 5 was the vehicle, and immediately after trauma, 1 mL of rice bran oil was injected. The animals were examined by inclined plane score and Basso-Beattie-Bresnahan scale 24 h after the trauma. At the end of the experiment, spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde (MDA) levels, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, and catalase (CAT) activity and pathological evaluation.. Curcumin treatment improved neurologic outcome, which was supported by decreased level of tissue MDA and increased levels of tissue GSH-Px, SOD, and CAT activity. Light microscopy results also showed preservation of tissue structure in the treatment group.. This study showed the neuroprotective effects of curcumin on experimental SCI model. By increasing tissue levels of GSH-Px, SOD, and CAT, curcumin seems to reduce the effects of injury to the spinal cord, which may be beneficial for neuronal survival.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Male; Neuroprotective Agents; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries