ATTENUATION OF BRAIN INJURY AND REDUCTION OF NEURON-SPECIFIC ENOLASE BY NICARDIPINE IN SYSTEMIC CIRCULATION FOLLOWING FOCAL ISCHEMIA AND REPERFUSION IN A RAT MODEL
M. Kittaka et al., ATTENUATION OF BRAIN INJURY AND REDUCTION OF NEURON-SPECIFIC ENOLASE BY NICARDIPINE IN SYSTEMIC CIRCULATION FOLLOWING FOCAL ISCHEMIA AND REPERFUSION IN A RAT MODEL, Journal of neurosurgery, 87(5), 1997, pp. 731-737
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.