Neuroprotective Effects of Alpha-Lipoic Acid in Experimental Spinal Cord Injury in Rats

Abstract

Background: Oxidative stress is a mediator of secondary injury to the spinal cord following trauma. Objective: To investigate the putative neuroprotective effect of ex-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI). Methods: Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (1 00 g/cm force) at T1 0 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. Results: SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged. Conclusion: The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.

Acrolein‐mediated injury in nervous system trauma and diseases

“…In the same injury model, severe axonal membrane damage was observed, but was not apparent until several days post-injury [49]. Toklu et al found myelin degradation at 7 days post-injury correlated with lipid peroxidation and DNA fragmentation [116]. These data are consistent with the hypothesis that diffusive elevation of acrolein precedes and leads to membrane disruption and subsequent cell death following in vivo spinal cord trauma.…”

Oxidative stress and antioxidative parameters in patients with spinal cord injury: implications in the pathogenesis of disease

“…These include methylene blue, mexilitine, thiopental, β-glucan, cyclosporine A, erythropoietin and α-lipoic acid. 34 Although some of these are probably true chemical antioxidants (for example, methylene blue, edaravone, α-lipoic acid), others may work indirectly by induction of endogenous antioxidant defenses (for example, N-acetylcysteine), reduction of mitochondrial dysfunction and its associated free-radical leakage (for example, cyclosporine A) or by enhancement of cell membrane repair mechanisms (for example, polyethylene glycol). All these data support the idea that antioxidant therapy may be beneficial in SCI patients.…”

Antioxidant Therapies for Acute Spinal Cord Injury

“…These include methylene blue [110], mexilitine [111], thiopental [112], β-glucan [113], N-acetylcysteine [114], γ-glutamylcysteine [18], polyethylene glycol [115], edaravone (MCI186), cyclosporine A [116], NIM811 [117,118], erythropoietin [119] and α-lipoic acid [120]. Although some of these are probably true chemical antioxidants (e.g., methylene blue, edaravone, α-lipoic acid), others may work indirectly by induction of endogenous antioxidant defenses (e.g., N-acetylcysteine, γ-glutamylcysteine), reduction of mitochondrial dysfunction, and its associated free radical leakage (e.g., cyclosporine A, NIM811) or by enhancement of cell membrane repair mechanisms (e.g., polyethylene glycol).…”