Cerebral infarction causes permanent neuronal loss inducing severe morbidity and mortality. Because
hypertension is the main risk factor for
cerebral infarction and most patients with
hypertension take
antihypertensive drugs daily, the
neuroprotective effects and mechanisms of
anti-hypertensive drugs need to be investigated.
Cilnidipine, a long-acting, new generation
1,4-dihydropyridine inhibitor of both L- and
N-type calcium channels, was reported to reduce oxidative stress. In this study, we investigated whether
cilnidipine has
therapeutic effects in an animal model of
cerebral infarction. After determination of the most effective dose of
cilnidipine, a total of 128 rats were subjected to
middle cerebral artery occlusion. Neurobehavioral function test and brain MRI were performed, and rats with similar sized
infarcts were randomized to either the
cilnidipine group or the control group.
Cilnidipine treatment was performed with reperfusion after 2-h occlusion. Western blots and immunohistochemistry were also performed after 24-h occlusion. Initial
infarct volume on diffusion-weighted MRI was not different between the
cilnidipine group and the control group; however, fluid-attenuated inversion recovery MRI at 24 h showed significantly reduced
infarct volume in the
cilnidipine group compared with the control group.
Cilnidipine treatment significantly decreased the number of
triphosphate nick end labeling-positive cells compared to the control group. Western blot and immunohistochemistry showed increased expression of phosphorylated Akt (Ser473), phosphorylated
glycogen synthase kinase-3β, and Bcl-2 and decreased expression of Bax and cleaved
caspase-3. These results suggest that
cilnidipine, which is used for the treatment of
hypertension, has
neuroprotective effects in the ischemic brain through activation of the PI3K pathway. We investigated whether
cilnidipine has
neuroprotective effects on
ischemic stroke in an animal model. We have demonstrated that the
neuroprotective effect of
cilnidipine is associated with the activation of the PI3K pathway. Considering the daily use of
antihypertensive drugs for patients with
hypertension,
cilnidipine could be beneficial for patients with
ischemic stroke.