We investigated the effects of
nilvadipine and
amlodipine on the
cerebral ischemia-induced impairment of spatial memory in 8-arm radial maze performance and hippocampal CA1 apoptosis in rats. Single
cerebral ischemia impaired memory without inducing apoptosis. In these rats, neither
nilvadipine nor
amlodipine at 3.2 mg/kg, i.p. improved the impaired memory. On the other hand, repeated
cerebral ischemia (10 min
ischemia x 2, 1 h interval) impaired spatial memory and induced hippocampal apoptosis 7 days after the final occlusion/reperfusion. Moreover, repeated
ischemia increased the apoptotic cell number, an effect observed after 3 days and peaked after 7 days. However,
mRNA expression of the apoptosis-related early oncogene bax and
CPP 32 (caspase-3) was observed after 24 h. In these rats,
nilvadipine, but not
amlodipine, significantly improved memory, concomitantly decreased hippocampal apoptosis, and suppressed both bax and
CPP 32 expression. These results suggest that
nilvadipine improved the memory impairment in repeated
ischemia by reducing bax and
CPP 32 expression and suppressing the induction of apoptosis in the hippocampus.
Nilvadipine may have a
neuroprotective effect and could be a useful pharmacotherapeutic agent for cerebrovascular
dementia.