Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function

The study aimed to 1) quantify oxidative stress in spinal cord after crush injury at T6, 2) determine whether the administration of the procysteine co mpound L-2-oxothiazolidine-4-carboxylate (OTC) would up-regulate glutathion e (GSH) synthesis and decrease oxidative stress, and 3) determine whether d ecreased oxidative stress results in better tissue and function retention. We demonstrate that spinal cord compression (5 s with a 50 g aneurysm clip) at T6 in rats results in oxidative stress that is extensive (significant i ncreases in oxidative stress seen at C3 and L4) and rapid in onset. Indices of oxidative stress used were GSH content, protein carbonyl content, and i nactivation of glutathione reductase. Administration of OTC resulted in a m arked decrease in oxidative stress associated with a sparing of white matte r at T6 (16 +/-1.9% retained in OTC-treated animals vs, less than 1% in sal ine-treated). Behavioral indices in control, saline-treated, and OTC-treate d animals after 6 wk were respectively: angle board scores (59 degrees, 32 degrees, and 42 degrees), modified Tarlov score (7, 2.4, and 4.1), and Bass o-Beattie-Bresnahan score (21, 5.3, and 12.9). We conclude that administrat ion of OTC after spinal cord trauma greatly decreases oxidative stress and allows tissue preservation, thereby enabling otherwise paraplegic animals t o locomote.