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(Stroke. 1995;26:282-289.)
© 1995 American Heart Association, Inc.

Articles

N^G-Nitro-L-Arginine Delays the Development of Brain Injury During Focal Ischemia in Rats

Ewa Kozniewska, PhD; Timothy P. L. Roberts, PhD; Mitsuharu Tsuura, MD; Jan Mintorovitch, PhD; Michael E. Moseley, PhD John Kucharczyk, PhD

From the Neuroradiology Section, Department of Radiology, University of California, San Francisco.

Correspondence to Ewa Kozniewska, PhD, Warsaw's School of Medicine, Department of Clinical and Applied Physiology, Krakowskie Przedmiescie 26/28, 00-927 Warsaw, Poland.

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 ischemia.

Methods Diffusion-weighted and contrast-enhanced, perfusion-sensitive magnetic resonance imaging was performed in anesthetized, mechanically ventilated rats at 30 minutes and 1, 2, and 3 hours after occlusion of the middle cerebral artery combined with coagulation of the basilar artery. At the onset of ischemia, the animals were infused intravenously 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-weighted 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 ischemia. The ADC in the injured cortex of nitro-L-arginine–treated rats did not differ significantly from the ADC value measured in the contralateral cortex until 3 hours after the occlusion. However, at 3 hours of ischemia the percentage decrease of ADC in both the striatum and the cortex of either group of rats was similar. This transient attenuation of ADC drop during ischemia after nitro-L-arginine pretreatment occurred concurrently with a transient improvement of blood supply to the ischemic regions. The percentage of hemispheric area with abnormal TTC staining after 3 hours of ischemia did not differ between control and nitro-L-arginine–treated rats.

Conclusions Nitro-L-arginine delays the development of ischemic injury by retarding cytotoxic brain edema. This effect is, at least partially, mediated by an improvement in blood supply to the ischemic tissues.

Key Words: brain edema • cerebral ischemia, focal • magnetic resonance imaging • nitric oxide synthesis • rats

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