iridoids and Spinal-Cord-Injuries

Spinal cord injury (SCI) is a disastrous central nervous system (CNS) disorder, which was intimately associated with oxidative stress. Studies have confirmed that Iridoids Effective Fraction of Valeriana jatamansi Jones (IEFV) can scavenge reactive oxygen species. This study aimed to confirm the efficacy of IEFV in ameliorating SCI.. For establish the SCI model, the Sprague-Dawley rats underwent a T10 laminectomy with transient violent oppression by aneurysm clip. Then, the rats received IEFV intragastrically for 8 consecutive weeks to evaluate the protective effect of IEFV on motor function, oxidative stress, inflammation and neurotrophic factors in SCI rats.. Basso, Beattie and Bresnahan scores, hematoxylin and eosin (H&E) staining and transmission electron microscopy experiments found IEFV protected motor function and alleviated neuron damage. Meanwhile, IEFV treatment decreased the release of malondialdehyde, interleukin-6 (IL-6), cyclooxygenase-2 and tumor necrosis factor-α. Moreover, IEFV treatment elevated the expression levels of brain-derived neurotrophic factor and nerve growth factor of SCI rats. Finally, administration of IEFV significantly inhibited the expression of p-p65 and toll-like receptor 4 (TLR4).. This study suggests that IEFV could attenuate the oxidative stress and inflammatory response of the spinal cord after SCI, which was associated with inhibition of the TLR4/nuclear factor-kappaB signaling pathway.

Topics: Animals; Female; Free Radical Scavengers; Iridoids; Male; Motor Activity; Neurons; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord; Spinal Cord Injuries; Valerian

Spinal cord injury (SCI) is a traumatic condition of the central nervous system , which can cause nerve injury and affect nerve regeneration, thus leading to severe dysfunction of motor and sensory pathways, and unfortunately these effects are irreversible. Inflammatory response constitutes one of the important mechanisms of spinal cord secondary injury. Geniposide (Gen) is reported to possess anti-inflammation and neuronal repair capacities.. To investigate the effect and mechanism of Gen on motor function and inflammatory response in SCI rats.. Sprague-Dawley (SD) rats were randomly grouped, and the SCI model was established by Allen's method. The motor function of rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale. The protective effect of Gen on the injured spinal cord tissues was evaluated by measuring the water content, myeloperoxidase (MPO) activity, and levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6. Moreover, the protein level of the inflammation-related pathway was detected by spectrometry and Western blot assays.. Gen significantly promoted the recovery of SCI rats, decreased the edema of spinal cord tissues, reduced the area of cavity, increased the number of NF-200-positive neurons, as well as increased the number of horseradish peroxidase (HRP) retrograde tracing-positive neurons and regenerated axons with myelin sheath. Additionally, compared with the control group, the neutrophil infiltration, contents of TNF-α, IL-1β, and IL-6, the activity of inhibitor of nuclear factor κB kinase subunit β (IKKβ) kinase, and protein levels of (nuclear factor κB) NF-κB p65 and phosphorylated inhibitor of NF-κB (p-I-κB) in the Gen experimental group were significantly decreased.. Gen effectively alleviated inflammatory response after SCI by inhibiting the IKKs/NF-κB signaling pathway and promoted the recovery of motor function and axon regeneration in rats.. This study can provide novel insights for the early and effective intervention of SCI and confer basic data for the treatment of spinal cord secondary injury.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Female; I-kappa B Kinase; Inflammation Mediators; Iridoids; Motor Activity; NF-kappa B; Rats, Sprague-Dawley; Recovery of Function; Signal Transduction; Spinal Cord; Spinal Cord Injuries; Spinal Cord Regeneration

Astrocytes can play dual roles in the response to spinal cord injury (SCI) acting as both an inhibitory barrier and a trophic support for growth axons. Therefore, migration of these cells into the defect as opposed to forming a scar at the periphery, may promote axon regeneration through the lesion. However, infiltration requires the conformal filling of the cyst-like lesion, which often forms after SCI, with a biomaterial scaffold encouraging of astrocyte migration. For this application, we investigated injectable collagen-based hydrogels covalently cross-linked with genipin and incorporating fibroblast growth factor-2 (FGF-2) either freely or encapsulated within lipid microtubules (LMTs). An outgrowth assay was used to evaluate in vitro the number of primary rat astrocytes infiltrating into the collagen gels and the distance to which they infiltrated. The presence of FGF-2 within the encapsulating gel significantly increased the number of astrocytes within the gel, their penetration distance into the gel, and caused them to move out in a chain-like pattern, compared to control gels without FGF-2. Genipin cross-linking of the collagen gel decreased the number of infiltrating astrocytes, compared to the non-cross-linked control gel; however, incorporation of FGF-2-containing LMTs within genipin-cross-linked gels restored the astrocyte infiltration to levels approaching non-cross-linked gels incorporating FGF-2. Overall, injectable collagen-genipin hydrogels containing FGF-2-containing LMTs are a promising candidate for the treatment for SCI through the attraction of astrocytes into the graft.

Topics: Animals; Astrocytes; Cell Survival; Cells, Cultured; Collagen; Fibroblast Growth Factor 2; Hydrogels; Iridoids; Nerve Regeneration; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Tissue Engineering

The aim of our work is to utilize the crosstalk between the vascular and the neuronal system to enhance directed neuritogenesis in uniaxial guidance scaffolds for the repair of spinal cord injury. In this study, we describe a method for angioneural regenerative engineering, i.e., for generating biodegradable scaffolds, produced by a combination of controlled freezing (freeze-casting) and lyophilization, which contain longitudinally oriented channels, and provide uniaxial directionality to support and guide neuritogenesis from neuronal cells in the presence of endothelial cells. The optimized scaffolds, composed of 2.5 % gelatin and 1 % genipin crosslinked, were characterized by an elastic modulus of ~51 kPa and longitudinal channels of ~50 μm diameter. The scaffolds support the growth of endothelial cells, undifferentiated or NGF-differentiated PC12 cells, and primary cultures of fetal chick forebrain neurons. The angioneural crosstalk, as generated by first forming endothelial cell monolayers in the scaffolds followed by injection of neuronal cells, leads to the outgrowth of long aligned neurites in the PC12/endothelial cell co-cultures also in the absence of exogenously added nerve growth factor. Neuritogenesis was not observed in the scaffolds in the absence of the endothelial cells. This methodology is a promising approach for neural tissue engineering and may be applicable for regenerative spinal cord injury repair.

Topics: Animals; Chick Embryo; Elastic Modulus; Endothelial Cells; Freeze Drying; Gelatin; Iridoids; Nerve Growth Factor; Neural Stem Cells; Neurogenesis; Neurons; PC12 Cells; Rats; Spinal Cord Injuries; Tissue Engineering; Tissue Scaffolds

Oleuropein (OE) is a well-known antioxidant polyphenol from olive oil. The purpose of this study was to determine the potential neuroprotective effects of oleuropein in an experimental spinal cord injury model.. Rats were randomly divided into four groups of 21 rats each as follows: sham-operated group, trauma group, and OE treatment groups (20 mg/kg, i.p., immediately and 1 hour after spinal cord injury). Spinal cord samples were taken 24 hours after injury and studied for determination of malondialdehyde and glutathione levels, histopathological assessment, immunohistochemistry of Bax and Bcl-2, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling reaction. Behavioral testing was performed weekly up to 6 weeks post-injury.. The results showed that malondialdehyde levels were significantly decreased, and glutathione levels were significantly increased in OE treatment groups. Greater Bcl-2 and attenuated Bax expression could be detected in the OE-treated rats. OE significantly reduced terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive reaction and improved behavioral function than the trauma group.. These findings indicate that OE may be effective in protecting rat spinal cord from secondary injury.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Disease Models, Animal; Female; Glutathione; Iridoid Glucosides; Iridoids; Lipid Peroxidation; Malondialdehyde; Neuroprotective Agents; Pyrans; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries

Several olive oil phenolic compounds, such us oleuropein have attracted considerable attention because of their antioxidant activity, anti-atherosclerotic and anti-inflammatory properties. The aim of this experimental study was to determine the effect of oleuropein aglycone, a hydrolysis product of oleuropein, in the inflammatory response, in particular in the secondary injury associated with the mouse model of spinal cord trauma. The injury was induced by application of vascular clips to the dura via a four-level T5-T8 laminectomy in mice. Oleuropein aglycone was administered in mice (100 μg/kg, 40 μg/kg, 20 μg/kg, 10% ethanol, i.p.) 1h and 6h after the trauma. The treatment with oleuropein aglycone significantly decreased: (1) histological damage, (2) motor recovery, (3) nuclear factor (NF)-κB expression and IKB-α degradation, (4) protein kinase A (PKA) activity and expression, (5) pro-inflammatory cytokines production such as tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β), 6) inducible nitric oxide synthase (iNOS) expression, (7) neutrophil infiltration, (8) lipid peroxidation, (9) nitrotyrosine and poly-ADP-ribose (PAR) formation, (10) glial cell-derived neurotrophic factor (GDNF) levels, (11) apoptosis (TUNEL staining, FAS ligand expression, Caspase 3, Bax and Bcl-2 expression). Thus, we propose that olive oil phenolic constituents such as oleuropein aglycone may be useful in the treatment of various inflammatory diseases.

Topics: Animals; Blotting, Western; In Situ Nick-End Labeling; Iridoid Glucosides; Iridoids; Male; Mice; Olive Oil; Plant Oils; Pyrans; Spinal Cord Injuries

Neutrophil infiltration plays an important role in inflammatory reactions following spinal cord injury (SCI) and these cells cause substantial secondary tissue damage. The purpose of this study was to determine the effect of oleuropein (OE) on myeloperoxidase (MPO) activity as an index of neutrophil infiltration.. Rats were randomly divided into four groups of 7 rats each as follows: sham-operated group, trauma group, and OE treatment groups (20 mg/kg, i.p., immediately and 1 hour after SCI). Spinal cord samples were taken 24 hours after injury and studied for determination of MPO activity.. The results showed that MPO activity was significantly decreased in OE-treated rats.. On the basis of our findings, we propose that OE may be effective in protecting rat spinal cord from secondary damage by modulating of neutrophil infiltration.

Topics: Animals; Iridoid Glucosides; Iridoids; Male; Peroxidase; Pyrans; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries