[Lack of evidence that inducible nitric oxide synthase participates in the development of ischemic brain damage]

We have already reported that the concentration of nitric oxide (NO) increases during and after cerebral ischemia and a selective inhibitor of neuronal NO synthase (nNOS) suppresses this increase and subsequently mitigates brain damage in rats. Although the selective inhibition of nNOS is a promising pharmacological strategy for the treatment of stroke, the role of inducible NOS (iNOS) remains to be clarified. Toward this end, we investigated temporal alterations in iNOS mRNA by the RT-PCR method in a rat model of middle cerebral artery (MCA) occlusion. We found that iNOS mRNA in the ischemic hemisphere began to increase at 3 hr and reached the maximum level at 24 hr of reperfusion following 3 hr of MCA occlusion. However, quantitative analysis revealed that no significant difference existed between 6 hr or 24 hr reperfusion group and their respective time-matched sham operation group. In addition, neither Western blotting nor immunocytochemical study disclosed an apparent induction of iNOS at any time points examined. Similar results were obtained at 24 hr of permanent MCA occlusion. Taken together, these data indicate that iNOS induction during and after MCA occlusion may be not a critical event for the development of infarction caused by ischemia itself.