N-G-NITRO-L-ARGININE DELAYS THE DEVELOPMENT OF BRAIN INJURY DURING FOCAL ISCHEMIA IN RATS

Background and Purpose The present study was designed to determine the effect of nitro-L-arginine, the inhibitor of nitric oxide synthesis, on the evolution of cytotoxic brain edema during focal cerebral ischem ia. Methods Diffusion-weighted and contrast-enhanced, perfusion-sensit ive magnetic resonance imaging was performed in anesthetized, mechanic ally ventilated rats at 30 minutes and 1, 2, and 3 hours after occlusi on of the middle cerebral artery combined with coagulation of the basi lar artery. At the onset of ischemia, the animals were infused intrave nously with 0.5 mL of either 0.9% NaCl or nitro-L-arginine (30 mg/kg). The severity of cytotoxic edema was evaluated based on changes in the water apparent diffusion coefficient (ADC) derived from diffusion-wei ghted images. The size of the area affected by ischemia was evaluated 3 hours after occlusion using 2,3,5-triphenyltetrazolium chloride (TTC ) staining. Results The percentage decrease of ADC in the striatum of rats pretreated with nitro-L-arginine was significantly smaller (P<.05 ) than in the control group at 30 minutes and 1 and 2 hours of ischemi a. The ADC in the injured cortex of nitro-L-arginine-treated rats did not differ significantly from the ADC value measured in the contralate ral cortex until 3 hours after the occlusion. However, at 3 hours of i schemia the percentage decrease of ADC in both the striatum and the co rtex of either group of rats was similar. This transient attenuation o f ADC drop during ischemia after nitro-L-arginine pretreatment occurre d concurrently with a transient improvement of blood supply to the isc hemic regions. The percentage of hemispheric area with abnormal TTC st aining after 3 hours of ischemia did not differ between control and ni tro-L-arginine-treated rats. Conclusions Nitro-L-arginine delays the d evelopment of ischemic injury by retarding cytotoxic brain edema. This effect is, at least partially, mediated by an improvement in blood su pply to the ischemic tissues.