NITRIC-OXIDE SYNTHASE INHIBITOR N-G-NITRO-L-ARGININE METHYL-ESTER DECREASES ISCHEMIC DAMAGE IN REVERSIBLE FOCAL CEREBRAL-ISCHEMIA IN HYPERGLYCEMIC RATS

We tested the hypothesis that the exacerbation of post-ischemic brain tissue injury associated with hyperglycemia in rats is due to toxic me tabolism of nitric oxide. We used magnetic resonance imaging (MRI) tec hniques to measure neuronal and cerebrovascular injury in a 2-h transi ent focal cerebral ischemia model in normoglycemic and hyperglycemic r ats at 3 and 24 h post-ischemia onset. We determined the effect of low dose (3 mg/kg i.p.) treatment with the nitric oxide synthase inhibito r N-G-nitro-L-arginine methyl ester (L-NAME). Compared to normoglycemi a, preexisting hyperglycemia increased the volume of brain tissue exhi biting hyperintensity in diffusion weighted MRI (DWI) by factors of 5. 6 and 6.2 at 3 h and 24 h post-ischemia, respectively. A similar incre ase in tissue volumes exhibiting hyperintense signal in T2-weighted MR I (T2WI) (3.3-fold and 5.6-fold) was observed. Cerebral blood volume M RI indicated a large focal no-reflow zone in hyperglycemic rats. Treat ment with L-NAME eliminated the no-reflow zone in the hyperglycemic ra ts, and reduced tissue volumes of DWI hyperintensity by 86% and 93% at 3 h and 24 h, respectively. Similarly, tissue volumes of T2WI hyperin tensity were reduced by 80% and 94% at 3 h and 24 h, respectively. Thu s, nitric oxide is an important mediator in the exacerbation of post-i schemic brain injury in hyperglycemic rats. Inhibition of nitric oxide synthase limits edema formation, improves perfusion and reduces infar ct volume.