Intrathecal Infusion of the Nitric Oxide Synthase InhibitorN-Methyll-Arginine after Experimental Spinal Cord Injury in Guinea Pigs

Abstract

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.

Role of peroxynitrite in secondary oxidative damage after spinal cord injury

“…2004). Evidences have shown that the administration of NOS inhibitors can exert a neuroprotective effect in the injured rat spinal cord and improve neurologic recovery (Cohen et al. 1996).…”

Increased Production of Tumor Necrosis Factor-αInduces Apoptosis after Traumatic Spinal Cord Injury in Rats

“…These results suggest that apoptosis is induced by TNF-a via induction of iNOS expression following NO production after SCI. However, Cohen et al (1996) reported that infusion of L-NMMA, an inhibitor of NOS, after SCI shows no beneficial effects on the degree or rate of secondary loss of spinal cord function and on the cross-sectional area of surviving white matter. Nevertheless, Bethea et al (1998) showed that iNOS immunoreactivity is co-localized with activated NF-kB in neurons after traumatic SCI.…”

Improved functional outcome after spinal cord injury in iNOS-deficient mice

“…8,9 Administration of inhibitors of NOS to experimentally spinal cord-injured animals has been reported to improve, 7,8 worsen 7 or have no effect on outcome measures. 10 The seemingly conflicting effects of different NOS inhibitors implicate a complex role of NO in postinjury tissue reactions. We are interested in the pathophysiology of traumatic SCI.…”