Iranian Journal of Medical Sciences

Document Type: Original Article(s)

Authors

1 Department of Physiology, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Pharmacology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

3 Medicinal & Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: The role of nitric oxide (NO) of endothelial or neuronal origins in cerebral ischemia and reperfusion injuries are far from being settled, extending from being important to not having any role at all.  Objective: To investigate the role of NO of endothelial and neuronal origins in ischemia/reperfusion injuries in focal cerebral ischemia, L-NAME, a non selective NO synthase inhibitor (NOS), and 7-nitroindazole (7-NI), a selective neuronal NOS were used. Methods: Transient focal cerebral ischemia was induced in rats by 90 min occlusion of middle cerebral artery, followed by 24 hr reperfusion. Vehicle (saline, DMSO), L-NAME (1 mg/kg) or 7-NI (50 mg/kg) was administered ip at 30 min before or 60 min after the onset of ischemia.  At the end of reperfusion period, neurological deficit score (NDS) test was performed. Then under deep anesthesia the brain removed and prepared for the evaluation of cortical and striatal infarct volumes using Triphenyltetrazolium chloride staining.  Results: Pre-ischemic administration of L-NAME significantly lowered cortical (-66±6%) and striatal (-45±12%) infarct volumes with a concomitant improved NDS (-38±10%).  A significant decrement in cortical (-39±7%) and striatal (-26±5%) infarct volumes occurred during post-ischemic administration of L-NAME without an improvement in NDS. Pre-ischemic administration of 7-NI also significantly reduced cortical (-37±10%) and striatal (-37±13%) infarct volumes, but did not change NDS significantly. Whereas, post-ischemic administrations of 7-NI neither changed cortical and striatal infarct volumes nor changed NDS. Conclusion: Our presumptive conclusion is that, in the rat model of transient focal cerebral ischemia, NO of neuronal origin is involved in ischemic and that of endothelial origin participates in reperfusion injuries.