Intrathecal infusion of the nitric oxide synthase inhibitor N-methyl L-arginine after experimental spinal cord injury in guinea pigs.
The potential role of nitric oxide (NO) production in secondary pathologic processes that follow spinal cord injury was examined in a guinea pig model that shows secondary loss of function for at least 3 days after trauma. Lateral compression injury of the lower thoracic cord was performed under ketamine/xylazine/acepromazine anesthesia. A fine polyethylene cannula was inserted through an incision in the dura rostral to the injury and run along the dorsal subdural space to the lesion level. The tube was connected to an osmotic pump delivering 1 microL/h of a 10 mM solution of either N-methyl-L-arginine or N-methyl-D-arginine in normal saline (pH 7.2). N-Methyl-L-arginine blocks both constitutive and inducible forms of NO synthase (NOS), present in neurons and inflammatory cells, respectively: N-methyl-D-arginine is the inactive stereoisomer. Two groups of 10 animals were used. Behavioral analysis and somatosensory evoked potential measurements were performed daily for 3 days, then the animals were fixed and survival of white matter at the center of the injury was evaluated, using toluidine-blue stained, 1 microns plastic sections. No significant difference was found between treated and control groups in degree or rate of secondary loss of spinal cord function or in the cross-sectional area of surviving white matter. These data do not support the hypothesis that local NO production by phagocytes, neurons, or other cells plays a significant role in secondary pathology of injury in this model.
Cohen
T I
TI
Division of Neurosurgery, University of North Carolina at Chapel Hill 27599, USA.
Weinberg
R J
RJ
Blight
A R
AR
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D007278:Injections, Spinal; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000473:pathology*
D001120:Arginine; D019001:Nitric Oxide Synthase