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 compound L-2-oxothiazolidine-4-carboxylate (OTC) would up-regulate glutathione (GSH) synthesis and decrease oxidative stress, and 3) determine whether decreased 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 increases in oxidative stress seen at C3 and L4) and rapid in onset. Indices of oxidative stress used were GSH content, protein carbonyl content, and inactivation of glutathione reductase. Administration of OTC resulted in a marked decrease in oxidative stress associated with a sparing of white matter at T6 (16+/-1.9% retained in OTC-treated animals vs. less than 1% in saline-treated). Behavioral indices in control, saline-treated, and OTC-treated 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 Basso-Beattie-Bresnahan score (21, 5.3, and 12.9). We conclude that administration of OTC after spinal cord trauma greatly decreases oxidative stress and allows tissue preservation, thereby enabling otherwise paraplegic animals to locomote.
Kamencic
H
H
Department of Anatomy, University of Saskatchewan, Saskatoon, SK, Canada.
Griebel
R W
RW
Lyon
A W
AW
Paterson
P G
PG
Juurlink
B H
BH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology*; D013117:Spinal Cord Compression / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D015854:Up-Regulation / Q000187:drug effects
D013844:Thiazoles; D053778:Thiazolidines; D005980:Glutathione Reductase; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid