Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury

Azbill, Robert D.; Mu, Xiaojun; Bruce‐Keller, Annadora J.; Mattson, Mark P.; Springer, Joe E.

doi:10.1016/s0006-8993(97)00573-8

Cited by 284 publications

(164 citation statements)

References 60 publications

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“…Decreased activity of Mn-SOD is a likely consequence of peroxynitrite after TBI, and could lead to further oxidative stress and progressively enhance peroxynitrite production as part of the secondary damage cascade [10]. Decreased activity of Cu/Zn-SOD in ipsilateral hippocampus of young animals post injury compromises defense capacities against oxidative stress [39].…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

Ansari

Roberts

Scheff

2008

Free Radical Biology and Medicine

272

211

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Oxidative stress, an imbalance between oxidants and antioxidants, contributes to the pathogenesis of traumatic brain injury (TBI). Oxidative neurodegeneration is a key mediator of exacerbated morphological responses and deficits in behavioral recoveries. The present study assessed early hippocampal sequential imbalance to possibly enhance antioxidant therapy. Young adult male Sprague-Dawley rats were subjected to a unilateral moderate cortical contusion. At various times post TBI, animals were killed and the hippocampus analyzed for antioxidants (GSH, GSSG, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, superoxide dismutase and catalase), and oxidants (acrolein,, protein carbonyl [PC] and 3-nitrotyrosine. Synaptic markers (synapsin-I, post synaptic density-95 [PSD-95], synapse associated protein-97 [SAP-97], growth associated protein-43 were also analyzed. All values were compared to sham operated animals. Significant time-dependent changes in antioxidants were observed as early as 3 h post trauma and paralleled increases in oxidants (4-HNE, acrolein and PC) with peak values obtained at 24-48 h. Time dependent changes in synaptic proteins (synapsin-I, PSD-95 and SAP-97) occurred well after levels of oxidants peaked. These results indicate that depletion of antioxidant systems following trauma could adversely affect synaptic function and plasticity. Early onset of oxidative stress suggests that the initial therapeutic window following TBI appears to be relatively short and it may be necessary to stagger selective types of anti-oxidant therapy to target specific oxidative components.

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Section: Discussionmentioning

confidence: 99%

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

Ansari

Roberts

Scheff

2008

Free Radical Biology and Medicine

272

211

View full text Add to dashboard Cite

show abstract

“…1 Oxidative stress occurs from a disequilibrium in the production of reactive oxygen species and antioxidative processes in favor of a production of oxidative radicals. The enzymatic and non-enzymatic antioxidant defense system, which includes catalase, superoxide dismutase (SOD) and glutathione (GSH) peroxidase, counteracts and regulates overall reactive oxygen species levels to maintain physiological homeostasis of cells and organ systems.…”

Section: Introductionmentioning

confidence: 99%

NMDA receptor blockage with 2-amino-5-phosphonovaleric acid improves oxidative stress after spinal cord trauma in rats

et al. 2009

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Study design: 2-amino-5-phosphonovaleric acid (APV) is an N-methyl-D-aspartate (NMDA) receptor blocker and has neuroprotective properties. This study is aimed at evaluating the effect of APV treatment on oxidative status after spinal cord injury (SCI). Methods: The experiment was carried out on the following five groups: Group1: sham operated, non-traumatized; Group2: with injured spinal cord, no treatment; Group3: with SCI, injected with 100 mg kg À1 APV; Group4: with SCI, injected with 200 mg kg À1 APV; and Group5: with SCI, injected with 400 mg kg À1 APV. SCI was inflicted by epidural compression with a cerebral vascular clip after T9-11 laminectomy. The experiments were completed after 12 h of trauma. Spinal cords were excised for evaluation of superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and malonyldialdehyde (MDA) levels. Results: After SCI, SOD and GSH levels decreased and the MDA level increased significantly. APV treatment decreased the MDA level and increased SOD, catalase and GSH levels. The maximum decrease in MDA was detected in the group treated with 100 mg kg À1 APV compared with the other groups. The GSH level was significantly increased in the group treated with 200 mg kg À1 APV. The SOD level was significantly increased in the group treated with 200 mg kg À1 APV. Conclusion:The results of this study have shown that APV treatment creates a dose-dependent antioxidant effect in rats with SCI and may be used for the treatment of SCIs.

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“…The decreased activity of SOD and GPx in SCI, as reported previous which could be due to increased consumption for free radicals' detoxification. In previous study, increased CAT activity in SCI has been shown [5,20]. We determined that CAT activity was insignificantly elevated as a result of SCI and this elevation was prevented by the treatment with dexmedetomidine.…”

Section: Discussionmentioning

confidence: 68%

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study

et al. 2009

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The aim of this experimental study was to investigate the possible protective effect of dexmedetomidine (DEX) on traumatic spinal cord injury (SCI). Twentytwo New Zealand rabbits were divided into three groups: sham (no drug or operation, n = 6), Control [SCI ? single dose of 1 mL saline intraperitoneally (i.p), after trauma; n = 8] and DEX (SCI ? 1 lg/kg dexmedetomidine in 1 mL, i.p, after trauma, n = 8). Laminectomy was performed at T10 and balloon angioplasty catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated by an independent observer according to the Tarlov scoring system. Blood, cerebrospinal fluid (CSF), tissue samples from spinal cord were taken for biochemical and histopathological evaluations. After 4 h of SCI, all animals in control or DEX treated groups became paraparesic. On the other hand, 24 h after SCI, partial improvements were observed in both control and DEX treated groups. Traumatic SCI leads to increase in the lipid peroxidation and decreases enzymatic or nonenzymatic endogenous antioxidative defense systems. Again, SCI leads to apoptosis in spinal cord. DEX treatment slightly prevented lipid peroxidation and augmented endogenous antioxidative defense systems in CSF or spinal cord tissue, but failed to prevent apoptosis or neurodeficit after traumatic SCI. Therefore, it could be suggested that treatment with dexmedetomidine does not produce beneficial results in SCI.

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Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury

Cited by 284 publications

References 60 publications

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

NMDA receptor blockage with 2-amino-5-phosphonovaleric acid improves oxidative stress after spinal cord trauma in rats

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study

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