N-methyl-D-aspartate Receptor Antagonists may Ameliorate Spinal Cord Injury by Inhibiting Oxidative Stress: An Experimental Study in Rats.

ABSTRACT

AIM: To investigate the neuroprotective effect of a N-methyl-D-aspartate (NMDA) receptor antagonist (amantadine) in an experimental spinal cord injury (SCI) model. MATERIAL AND METHODS: Thirty male Spragueâ€"Dawley rats were divided into three groups control (I), SCI (II), and SCI + amantadine (III). SCI was created using clip compression technique. At the end of day 7, blood samples were obtained from the rats and analyzed using various biochemical markers. Histological examination was also performed. MDA, GSH, and MPO assays were done. VEGF, TNF-α, and Baxexpressions were also analyzed. RESULTS: The group III had several inflammatory cells in the gray and white matter, with mildly degenerated multipolar and bipolar cells. Some bipolar and multipolar neurons showed TNF-α expression; however, TNF-α was found to be weak in small groups of inflammatory cells around the blood vessels in the substantia grisea and alba. Positive Bax expression was observed in the substantia grisea layer, particularly in the membrane of some bipolar neurons and glial cells; however, negative Bax expression was observed in neuron and glial cells and showed positive VEGF expression in the vascular endothelium in the group III. CONCLUSION: NMDA receptor antagonists, especially amantadine, may ameliorate SCI by inducing angiogenesis, affecting inflammation and apoptosis. It inhibits oxidative stress and the signaling pathways following SCI in rats.