Role of protein kinase C in thedevelopment of ischemic brain edema

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To clarify the oile of protein kinase C (PKC) in the development of ischemic brain edema, we examined protein kinase C activity, Na^+/K^+-ATPase activity and brain water content in focal cerebral ischemia in the rat.Focal carebral ishemia was induced by the occlusion of the right middle cerebral artery (MCA occlusion).While PKC activity in the ischemic areas did mot sihnificantly change compared to preischemic levels at 2 hours after MCA occlusion, PKC activity in the ischemic areas significantly decreased in both cytosole and membrane fraction compared to preischemic levels at 4 hours after MCA occlusion(p<0.001).Na^+/K^+-ATPase activity in the ischemic cerebral hemispheres decreased in comparison to the non-ischemic cerebral hemisphere at 4 hours after MCA occlusion. PKC activator, phorbol 12-myristate 13-acetate (PMA), elicited an increase of the level of Na^+/K^+-ATPase activity in the ischemic cerebral hemisphere to the level present in the non-ischemic cerebral hemisphere. Four hours after MCA occlusion, brain water content in the ischemic cerebral himisphere significantly increased compared to the preischemic level. pretreatment with PMA prevented an increase in water content in the ischemic hemishere at 4 hours after MCA occlusion. On the other hand, pretreatment with PKC inhibitor, H-7 and ataurosporine, did not prevent an increase in brain water content in the ischemic hemispere at 4 hours after MCA occlusion.These results suggest that protein kinase C regulates Na^+/K^+-ATPasa activity and that decreased activity of PKC in cerebral ischemia induces the reduction if Na^+/K^+-ATPase activity, leading to the development of ischemic brain edema.