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The Journal of surgical research

Neuroprotective mechanism of ischemic postconditioning in mice: a possible relationship between protein kinase C and nitric oxide pathways.


PMID 24655662

Abstract

The present study was conducted to pharmacologically investigate the role of protein kinase C (PKC) pathway in neuroprotective mechanism of ischemic postconditioning (iPoCo) and determine the influence of nitric oxide (NO) signaling in PKC-mediated effects. Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was used to produce ischemia and reperfusion (I/R)-induced cerebral injury in male Swiss mice. Memory was assessed using Morris water maze test. Degree of motor incoordination was evaluated using inclined beam-walk test, rota-rod test, and lateral push test. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Brain acetylcholinesterase activity, thiobarbituric acid reactive species, nitrite/nitrate, and reduced glutathione levels were also estimated. Bilateral carotid artery occlusion followed by reperfusion produced significant rise in cerebral infarct size, acetylcholinesterase activity, and thiobarbituric acid reactive species levels along with the fall in nitrite/nitrate and glutathione 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 incoordination, and altered biochemicals. iPoCo-induced neuroprotective effects were significantly abolished by chelerythrine (a nonselective PKC inhibitor). L-Arginine, an NO precursor significantly attenuated I/R-induced injury and mimicked the neuroprotective effect of postconditioning. Furthermore, this protective effect of L-arginine on I/R injury and iPoCo was abolished when it was coadministered with chelerythrine. It may be concluded that neuroprotective mechanism of iPoCo involves PKC mediated pathway with NO signaling as an essential step.

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Chelerythrine chloride, ≥95% (TLC), powder
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