Effects of central inhibition of nitric oxide synthase on focal cerebral ischemia in rats

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
J HamadaM Reivich

Abstract

We have investigated whether central inhibition of nitric oxide synthase (NOS) could modify the tissue damage of focal cerebral ischemia produced by occlusion of the middle cerebral artery (MCA) in rats. NG-Nitro-L-arginine methyl ester (L-NAME) was administered intracerebroventricularly at two doses 15 min prior to occlusion of the MCA, as well as 4 and 24 h following occlusion. After the injection of L-NAME, the catalytic activity of the constitutive NOS, considered to be mainly neuronal, was effectively suppressed in the subcortical gray matter bilaterally, but not in the ischemic territory. Seven days after the MCA occlusion, the brains were evaluated for histopathologic damage. High-dose administration of L-NAME (120 micrograms/kg 15 min prior to MCA occlusion, followed by 150 micrograms/kg 4 and 24 h after occlusion) produced an enlargement of the infarct area and increased the volume of ischemic damage. These results indicate that extensive inhibition of NOS by a central route can increase the cerebral infarct size in focal ischemia even if NOS is not inhibited in the ischemic tissue and suggest that NO may also play a potentially beneficial role as well as a neurodestructive role in the pathophysiological mechanisms of ...Continue Reading

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Citations

Jan 21, 2009·Molecular Neurobiology·Jean Lud Cadet, Irina N Krasnova
Jun 5, 2003·Experimental Neurology·Masatoshi YunokiKevin S Lee
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Jan 14, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·W Paschen, J Doutheil

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