ATTENUATION OF BRAIN INJURY AND REDUCTION OF NEURON-SPECIFIC ENOLASE BY NICARDIPINE IN SYSTEMIC CIRCULATION FOLLOWING FOCAL ISCHEMIA AND REPERFUSION IN A RAT MODEL

A reversible middle cerebral artery occlusion was performed in rats to determine whether nicardipine, a dihydropyridine voltage-sensitive Ca ++ channel (VSCC) antagonist, exerts neuroprotective effects when admi nistered 10 minutes following an ischemic insult, and if it does, whet her this is due to its vasodilatory action and effect on cerebral bloo d flaw (CBF) or to direct blockade of Ca++ entry into ischemic brain c ells. An increase in the intracellular calcium, [Ca++](i), plays a maj or role in neuronal injury during cerebral ischemia. Although a large amount of Ca++ enters neurons through the VSCC during ischemia, incons istent neuroprotective effects have been reported with the antagonists of the VSCC. An intraperitoneal injection of nicardipine (1.2 mg/kg) was administered to rats 10 minutes after the onset of ischemia, and 8 , 16, and 24 hours after occlusion. Cortical CBF was determined by las er-Doppler flowmetry. Neurological and neuropathological examinations were performed after 72 hours. Neuron-specific enolase, a specific mar ker for the incidence of neuronal injury, was measured in plasma. The CBF and other physiological parameters were not affected by nicardipin e during occlusion or reperfusion. However, nicardipine treatment sign ificantly improved motor neurological outcome by 29%, and the infarcti on and edema volume in the pallium as well as the edema volume in the striatum were significantly reduced by 27%, 37%, and 52%, respectively . Nicardipine also reduced the neuron-specific enolase plasma levels b y 50%, 42%, and 59% at 24, 48, and 72 hours after the occlusion, respe ctively. It is concluded that nicardipine may attenuate focal ischemic brain injury by exerting direct neuroprotective and antiedematous eff ects that do not depend on CBF.