curcumin and Brain-Injuries

Neurodegenerative disorders and diseases (NDDs) that are either chronically acquired or triggered by a singular detrimental event are a rapidly growing cause of disability and/or death. In recent times, there have been major advancements in our understanding of various neurodegenerative disease states that have revealed common pathologic features or mechanisms. The many mechanistic parallels discovered between various neurodegenerative diseases suggest that a single therapeutic approach may be used to treat multiple disease conditions. Of late, natural compounds and supplemental substances have become an increasingly attractive option to treat NDDs because there is growing evidence that these nutritional constituents have potential adjunctive therapeutic effects (be it protective or restorative) on various neurodegenerative diseases. Here we review relevant experimental and clinical data on supplemental substances (i.e., curcuminoids, rosmarinic acid, resveratrol, acetyl-L-carnitine, and ω-3 (n-3) polyunsaturated fatty acids) that have demonstrated encouraging therapeutic effects on chronic diseases, such as Alzheimer's disease and neurodegeneration resulting from acute adverse events, such as traumatic brain injury.

Topics: Acetylcarnitine; Alzheimer Disease; Brain; Brain Injuries; Cinnamates; Cognition Disorders; Curcumin; Depsides; Diet; Dietary Supplements; Fatty Acids, Omega-3; Humans; Neurodegenerative Diseases; Oxidative Stress; Polyphenols; Resveratrol; Rosmarinic Acid; Stilbenes

Exercise and select diets have important influences on health and plasticity of the nervous system, and the molecular mechanisms involved with these actions are starting to be elucidated. New evidence indicates that exercise, in combination with dietary factors, exerts its effects by affecting molecular events related to the management of energy metabolism and synaptic plasticity.. Published studies in animals and humans describing the effects of exercise and diets in brain plasticity and cognitive abilities are discussed.. New evidence indicates that exercise and select diets exert their effects by affecting molecular events related to the management of energy metabolism and synaptic plasticity. An important instigator in the molecular machinery stimulated by exercise is brain-derived neurotrophic factor (BDNF), which acts at the interface of metabolism and plasticity.. Recent studies show that selected dietary factors share similar mechanisms with exercise, and in some cases they can complement the action of exercise. Therefore, exercise and dietary management appear as a non-invasive and effective strategy to counteract neurological and cognitive disorders.

Topics: Animals; Brain Injuries; Brain-Derived Neurotrophic Factor; Cognition Disorders; Curcumin; Diet; Dietary Supplements; Docosahexaenoic Acids; Energy Metabolism; Exercise; Fatty Acids, Omega-3; Food; Humans; Motor Activity; Nervous System Diseases; Neuronal Plasticity

Diabetes mellitus has been implicated in the exacerbation of cerebral ischemic injuries. Among the most promising therapeutic approaches is the combination of nutraceuticals and nanotechnology. Curcumin has been termed "the magic molecule", and it was proven to exert several therapeutic actions. Therefore, the aim of the presented work was to investigate the therapeutic effects of curcumin nanoemulsion (NC) administered orally on the middle cerebral artery occlusion and reperfusion (MCAO/Re)-induced cerebral damage in rats with streptozotocin-induced diabetes. The cerebral injury was induced in rats by MCAO/Re 6 weeks after single intraperitoneal STZ injection (50 mg/kg; i.p.). MCAO/Re diabetic rats were then treated with NC (50 and 100 mg/kg; bw; p.o.) for two consecutive weeks. The results of the present study showed that oral treatment of MCAO/Re diabetic rats with NC was associated with a marked attenuation of the neurological deficit score as well as the brain imbalance of the redox homeostasis. NC treatment was also associated with decline in the brain expression of tumor necrosis factor, interleukin-1β, COX-2, cleaved caspase-3, and nuclear factor kappa B. In addition, the expression of glucose transporter 1 proteins upon treatment was restored. PRACTICAL APPLICATIONS: From all these results, it can be concluded that oral supplementation of curcumin nanoemulsion (NC) in diabetic rats reduced the brain injury via augmentation of the expression of glucose transporter 1, as well as its antioxidant and anti-inflammatory properties. Therefore, NC could be delineated as a promising treatment option for cerebral ischemia in diabetic patients.

Topics: Animals; Brain Injuries; Curcumin; Diabetes Mellitus, Experimental; Glucose Transporter Type 1; Infarction, Middle Cerebral Artery; Rats; Reperfusion Injury

Topics: Apoptosis; Brain Edema; Brain Injuries; Cerebral Hemorrhage; Curcumin; Humans; Janus Kinase 1; Neuroinflammatory Diseases; Neurons; STAT1 Transcription Factor

Topics: Animals; Aquaporin 4; Astrocytes; Brain; Brain Edema; Brain Injuries; Chronic Disease; Corticosterone; Curcumin; Disease Models, Animal; Gliosis; Hypoxia; Male; Mice, Inbred BALB C; Neurons; Neuroprotective Agents; p38 Mitogen-Activated Protein Kinases; Random Allocation; Signal Transduction

Objective To investigate the inhibitory effect of curcumin on early brain injury following subarachnoid hemorrhage (SAH) by inhibiting JNK/ c-Jun signal pathway. Methods Sixty adult male SD rats were randomly divided into four groups: sham operation group (sham group), SAH group, SAH group treated with 100 mg/(kg.d) curcumin and SAH group treated with 200 mg/(kg.d) curcumin, with 15 rats in each group. Endovascular puncture was used to induce SAH model. Nissl staining was used to test whether neurons were broken. TUNEL staining was used to detect apoptosis. Immunohistochemistry was used to investigate the expression of caspase-3. Western blot analysis was used to detect the expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3. Results Nissl staining indicated the decrease of Nissl bodies in SAH group, but increase of Nissl bodies in SAH group treated with curcumin. TUNEL staining showed that there were more apoptotic neurons in SAH group compared with sham group, while apoptotic neurons decreased after the treatment with curcumin, more obviously in the group treated with 200 mg/(kg.d) curcumin. The expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3 were up-regulated in SAH group compared with sham group. However, the expressions of those proteins were down-regulated after the treatment with curcumin, especially by higher-dose curcumin treatment. Conclusion Curcumin might suppress early brain injury after SAH by inhibiting JNK/c-Jun signal pathway and neuron apoptosis.

Topics: Animals; Apoptosis; Brain Injuries; Caspase 3; Curcumin; Humans; Male; MAP Kinase Kinase 4; Proto-Oncogene Proteins c-jun; Rats; Rats, Sprague-Dawley; Signal Transduction; Subarachnoid Hemorrhage

More and more evidence revealed early brain injury (EBI) may determine the final outcome in aneurismal subarachnoid hemorrhage (SAH) patients. This study is of interest to examine the efficacy of nano-particle curcumin (nanocurcumin), a diarylheptanoid, on a SAH-induced EBI model.. A rodent double hemorrhage model was employed. Nanocurcumin (75/150/300μg/kg/day) was administered via osmotic mini-pump post-SAH. CSF samples were collected to examine IL-1β, IL-6, IL-8 and TNF-α (rt-PCR). Cerebral cortex was harvested for NF-κB (p50/p65) (western blot), caspases (rt-PCR) measurement.. Nanocurcumin significantly reduced the bio-expression of NF-κB (p65), when compared with the SAH groups. The levels of IL-1β and IL-6 were increased in animals subjected to SAH, compared with the healthy controls, but absent in the high dose nanocurcumin+SAH group. Moreover, the levels of TNF-α in the SAH groups were significantly elevated. Treatment with nanocurcumin (300μg/kg) reduced the level to the healthy control. The cleaved caspase-3 and -9a was significantly reduced in 300μg/kg nanocurcumin treatment groups (P<0.05).. Treatment with nanocurcumin exerts its neuroprotective effect through the upward regulation of NF-κB (p65) and also reduced mitochondrion related caspase-9a expression. Besides, nanocurcumin decreased CSF levels of TNF-α and IL-1β, which may contribute to the extrinsic antiapoptotic effect. This study shows promise to support curcuminin, in a nano-particle, could attenuate SAH induced EBI.

Topics: Analysis of Variance; Animals; Biocompatible Materials; Brain Injuries; Caspase 3; Caspase 9; Curcumin; Cytokines; Disease Models, Animal; Down-Regulation; Enzyme Inhibitors; Lactic Acid; Male; Neurologic Examination; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Sprague-Dawley; RNA, Messenger; Subarachnoid Hemorrhage; Transcription Factor RelA

Curcumin, extracted from South Asian spice turmeric, has been determined to have the promising ability in antioxidation and anti-inflammation. However, the effect of curcumin on treating brain damage has been not reported. In this article, the aim was to evaluate the effect of curcumin on cell apoptosis in rats exposed to hypoxia-hypercapnia and explore the therapeutic potential of curcumin in hypoxia-hypercapnia brain damage (HHBD). Sprague Dawley rats were randomly assigned into 3 groups: control group, hypoxia-hypercapnia group and curcumin group. The Fas/FasL expressions in HHBD rats treated by curcumin were measured by immunohistochemical staining and western blotting. The pathological changes of brain cells were observed by transmission electron microscope. Rats with HHBD showed significant increase of Fas/FasL expression and ultrastructural changes in brain tissue cells. Curcumin intervention effectively reversed the Fas/FasL-mediated apoptosis and HHBD-induced brain edema. Curcumin may be a potential therapeutic alternative for HHBD.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Brain Edema; Brain Injuries; Curcumin; Disease Models, Animal; Fas Ligand Protein; fas Receptor; Gene Expression Regulation; Hypercapnia; Hypoxia; Male; Rats; Rats, Sprague-Dawley

Damage to the plasma membrane is a prevalent but often neglected aspect of traumatic brain injury (TBI), which can impair neuronal signaling and hamper neurological recovery.. This study was performed to assess a new noninvasive intervention to counteract peroxidative damage to the phospholipids in the membrane using the powerful action of foods. Although dietary docosahexaenoic acid (C22:6n-3; DHA) provides protection against TBI, the pervasive effects of TBI that cause phospholipid damage, including to DHA, raises concerns about how to preserve DHA in the brain for optimal functional recovery.. Rats were maintained on curcumin and/or DHA-enriched diets for 2 weeks postinjury, and their brains were subjected to analyses.. Fluid percussion injury reduced DHA levels as well as levels of enzymes involved in the metabolism of DHA such as FADS2 and 17β-HSD4 and elevated levels of markers of lipid peroxidation such as 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE). These effects were counteracted by DHA or curcumin, whereas the combination of curcumin and DHA had an enhanced effect on DHA and 4-HNE. The combination of curcumin and DHA was also efficient in counteracting reductions in the plasticity markers, brain-derived neurotrophic factor and its receptor p-trkB, and learning ability, which had been lessened after TBI.. Curcumin complements the action of DHA on TBI pathology, and this property appears to be a viable strategy to counteract neuronal dysfunction after TBI and complement the application of rehabilitative interventions to foster functional recovery.

Topics: Animals; Brain Injuries; Brain-Derived Neurotrophic Factor; Cell Membrane; Cognition; Curcumin; Docosahexaenoic Acids; Male; Maze Learning; Neuronal Plasticity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Recovery of Function

Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI.. Neurological function, brain water content and cytokine levels were tested in TLR4⁻/⁻ mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation.. The protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4⁻/⁻ mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and neuron co-culture following treatment with curcumin after LPS stimulation. LPS increased TLR4 immunoreactivity and morphological activation in microglia and increased neuronal apoptosis, whereas curcumin normalized this upregulation. The increased protein levels of TLR4, MyD88 and NF-κB in microglia were attenuated by curcumin treatment.. Our results suggest that post-injury, curcumin administration may improve patient outcome by reducing acute activation of microglia/macrophages and neuronal apoptosis through a mechanism involving the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages in TBI.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain Edema; Brain Injuries; Cells, Cultured; Cerebral Cortex; Coculture Techniques; Curcumin; Disease Models, Animal; Down-Regulation; Embryo, Mammalian; Encephalitis; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myeloid Differentiation Factor 88; Signal Transduction; Time Factors; Toll-Like Receptor 4

Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow coloring principle in turmeric, is a polyphenolic and a major active constituent. Besides anti-inflammatory, thrombolytic and anti-carcinogenic activities, curcumin also possesses strong antioxidant property. The neuroprotective effects of curcumin were evaluated in a weight drop model of cortical contusion trauma in rat. Male Wistar rats (350-400 g, n=9) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and subjected to head injury. Five days before injury, animals randomly received an i.p. bolus of either curcumin (50 and 100 mg/kg/day, n=9) or vehicle (n=9). Two weeks after the injury and drug treatment, animals were sacrificed and a series of brain sections, stained with hematoxylin and eosin (H&E) were evaluated for quantitative brain lesion volume. Two weeks after the injury, oxidative stress parameter (malondialdehyde) was also measured in the brain. Curcumin (100 mg/kg) significantly reduced the size of brain injury-induced lesions (P<0.05). Neurological examinations (rotarod and inclined-plane tests) were performed on days 1, 3, 7 and 14 post-brain injury. Control injured rats had a significant neurological deficit during 2 weeks (P<0.001). The injury increased brain levels of the malondialdehyde by 35.6% and these increases were attenuated by curcumin (100 mg/kg). Curcumin treatment significantly improved the neurological status evaluated during 2 weeks after brain injury. The study demonstrates the protective efficacy of curcumin in rat traumatic brain injury model.

Topics: Animals; Behavior, Animal; Brain; Brain Injuries; Curcumin; Lipid Peroxidation; Locomotion; Male; Oxidative Stress; Rats; Rats, Wistar; Rotarod Performance Test

In addition to cognitive dysfunction, locomotor deficits are prevalent in traumatic brain injured (TBI) patients; however, it is unclear how a concussive injury can affect spinal cord centers. Moreover, there are no current efficient treatments that can counteract the broad pathology associated with TBI.. The authors have investigated potential molecular basis for the disruptive effects of TBI on spinal cord and hippocampus and the neuroprotection of a curcumin derivative to reduce the effects of experimental TBI.. The authors performed fluid percussion injury (FPI) and then rats were exposed to dietary supplementation of the curcumin derivative (CNB-001; 500 ppm). The curry spice curcumin has protective capacity in animal models of neurodegenerative diseases, and the curcumin derivative has enhanced brain absorption and biological activity.. The results show that FPI in rats, in addition to reducing learning ability, reduced locomotor performance. Behavioral deficits were accompanied by reductions in molecular systems important for synaptic plasticity underlying behavioral plasticity in the brain and spinal cord. The post-TBI dietary supplementation of the curcumin derivative normalized levels of BDNF, and its downstream effectors on synaptic plasticity (CREB, synapsin I) and neuronal signaling (CaMKII), as well as levels of oxidative stress-related molecules (SOD, Sir2).. These studies define a mechanism by which TBI can compromise centers related to cognitive processing and locomotion. The findings also show the influence of the curcumin derivative on synaptic plasticity events in the brain and spinal cord and emphasize the therapeutic potential of this noninvasive dietary intervention for TBI.

Topics: Animals; Brain Injuries; Cognition Disorders; Curcumin; Disease Models, Animal; Gait Disorders, Neurologic; Male; Neuroprotective Agents; Paresis; Pyrazoles; Rats; Rats, Sprague-Dawley

Traumatic brain injury is a devastating neurological injury associated with significant morbidity and mortality. Medical therapies to limit cerebral edema, a cause of increased intracranial hypertension and poor clinical outcome, are largely ineffective, emphasizing the need for novel therapeutic approaches. In the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 min post-treatment with 300 mg/kg significantly reduced brain water content and improved neurological outcome following a moderate controlled cortical impact in mice. The protective effect of curcumin was associated with a significant attenuation in the acute pericontusional expression of interleukin-1beta, a pro-inflammatory cytokine, after injury. Curcumin also reversed the induction of aquaporin-4, an astrocytic water channel implicated in the development of cellular edema following head trauma. Notably, curcumin blocked IL-1beta-induced aquaporin-4 expression in cultured astrocytes, an effect mediated, at least in part, by reduced activation of the p50 and p65 subunits of nuclear factor kappaB. Consistent with this notion, curcumin preferentially attenuated phosphorylated p65 immunoreactivity in pericontusional astrocytes and decreased the expression of glial fibrillary acidic protein, a reactive astrocyte marker. As a whole, these data suggest clinically achievable concentrations of curcumin reduce glial activation and cerebral edema following neurotrauma, a finding which warrants further investigation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aquaporin 4; Blotting, Western; Brain Edema; Brain Injuries; Cells, Cultured; Curcumin; Immunohistochemistry; Interleukin-1beta; Learning; Male; Memory; Mice; Microscopy, Confocal; NF-kappa B; Recognition, Psychology; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction

We have assessed potential mechanisms associated with the deleterious effects of TBI on the integrity of plasma membranes in the hippocampus, together with consequences for behavioral function. In addition, we have investigated the efficacy of a dietary intervention based on a pyrazole curcumin derivative with demonstrated bioactivity and brain absorption, to re-establish membrane integrity. We report that moderate fluid percussion injury (FPI) increases levels of 4-Hydroxynonenal (HNE), an intermediary for the harmful effects of lipid peroxidation on neurons. A more direct action of FPI on membrane homeostasis was evidenced by a reduction in calcium-independent phospholipase A2 (iPLA₂) important for metabolism of membrane phospholipids such as DHA, and an increase in the fatty acid transport protein (FATP) involved in translocation of long-chain fatty acids across the membrane. A potential association between membrane disruption and neuronal function was suggested by reduced levels of the NR2B subunit of the transmembrane NMDA receptor, in association with changes in iPLA2 and syntaxin-3 (STX-3, involved in the action of membrane DHA on synaptic membrane expansion). In addition, changes in iPLA2, 4-HNE, and STX-3 were proportional to reduced performance in a spatial learning task. In turn, the dietary supplementation with the curcumin derivative counteracted all the effects of FPI, effectively restoring parameters of membrane homeostasis. Results show the potential of the curcumin derivative to promote membrane homeostasis following TBI, which may foster a new line of non-invasive therapeutic treatments for TBI patients by endogenous up-regulation of molecules important for neural repair and plasticity.

Topics: Aldehydes; Animals; Behavior, Animal; Blotting, Western; Brain Injuries; Cell Membrane; Cognition; Curcumin; Homeostasis; Immunohistochemistry; Lipid Peroxidation; Male; Maze Learning; Nerve Tissue Proteins; Neuronal Plasticity; Pyrazoles; Rats; Rats, Sprague-Dawley; Synapses

Traumatic brain injury (TBI) is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. New research indicates that events that regulate energy homeostasis crucially impact synaptic function and this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The goal of the present study is to determine the influence of the phenolic yellow curry pigment curcumin on molecular systems involved with the monitoring, balance, and transduction of cellular energy, in the hippocampus of animals exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham, RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats. The curcumin diet counteracted the effects of FPI and elevated the levels of AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show the potential of curcumin to regulate molecules involved in energy homeostasis following TBI. These studies may foster a new line of therapeutic treatments for TBI patients by endogenous upregulation of molecules important for functional recovery.

Topics: AMP-Activated Protein Kinase Kinases; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Brain Injuries; Creatine Kinase, Mitochondrial Form; Curcumin; Diet; Electron Transport Complex IV; Hippocampus; Homeostasis; Immunohistochemistry; Male; Phosphorylation; Protein Kinases; Random Allocation; Rats; Rats, Sprague-Dawley; Sirtuin 1; Sirtuins

The pervasive action of oxidative stress on neuronal function and plasticity after traumatic brain injury (TBI) is becoming increasingly recognized. Here, we evaluated the capacity of the powerful antioxidant curry spice curcumin ingested in the diet to counteract the oxidative damage encountered in the injured brain. In addition, we have examined the possibility that dietary curcumin may favor the injured brain by interacting with molecular mechanisms that maintain synaptic plasticity and cognition. The analysis was focused on the BDNF system based on its action on synaptic plasticity and cognition by modulating synapsin I and CREB. Rats were exposed to a regular diet or a diet high in saturated fat, with or without 500 ppm curcumin for 4 weeks (n = 8/group), before a mild fluid percussion injury (FPI) was performed. The high-fat diet has been shown to exacerbate the effects of TBI on synaptic plasticity and cognitive function. Supplementation of curcumin in the diet dramatically reduced oxidative damage and normalized levels of BDNF, synapsin I, and CREB that had been altered after TBI. Furthermore, curcumin supplementation counteracted the cognitive impairment caused by TBI. These results are in agreement with previous evidence, showing that oxidative stress can affect the injured brain by acting through the BDNF system to affect synaptic plasticity and cognition. The fact that oxidative stress is an intrinsic component of the neurological sequel of TBI and other insults indicates that dietary antioxidant therapy is a realistic approach to promote protective mechanisms in the injured brain.

Topics: Analysis of Variance; Animals; Blotting, Western; Brain Injuries; Brain-Derived Neurotrophic Factor; Cognition Disorders; Curcumin; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Hippocampus; Male; Models, Biological; Neuronal Plasticity; Neuroprotective Agents; Neuropsychological Tests; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reaction Time; Synapsins