Gulati_2014_J.Surg.Res_188_349

BACKGROUND: The present study was conducted to pharmacologically investigate the isoform-specific role of nitric oxide pathway in neuroprotective mechanism of ischemic postconditioning (iPoCo). MATERIALS AND
METHODS: Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was used to produce ischemia- and reperfusion-induced cerebral injury in male Swiss mice. Memory was assessed using Morris water maze test. Degree of motor in-coordination was evaluated using inclined beam-walk test, rotarod test, and lateral push test. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Brain acetylcholinestrase activity, thiobarbituric acid-reactive species, nitrite/nitrate, and reduced glutathione levels were also estimated. Western blotting was performed to determine endothelial nitric oxide synthase (eNOS) expression.
RESULTS: Bilateral carotid artery occlusion followed by reperfusion produced significant rise in cerebral infarct size, acetylcholinesterase activity, and thiobarbituric acid-reactive species levels along with fall in nitrite/nitrate, and glutathione and eNOS expression levels. A significant impairment of memory and motor coordination was also noted. iPoCo consisting of three episodes of 10-s carotid artery occlusion and reperfusion significantly attenuated infarct size, memory impairment, motor in-coordination, altered biochemicals, and protein expression levels. iPoCo-induced neuroprotective effects were significantly abolished by l-NAME (a nonselective nitric oxide synthase inhibitor) and l-NIO (a selective eNOS inhibitor). However, aminoguanidine (a selective inducible nitric oxide synthase inhibitor) and 7-nitroindazole (a selective neuronal nitric oxide synthase inhibitor) did not modulate beneficial effects of iPoCo.
CONCLUSIONS: It may be concluded that nitric oxide pathway probably plays a vital role with specific involvement of eNOS in neuroprotective mechanism of iPoCo.