Neuroprotection by lomerizine, a prophylactic drug for migraine, against hydrogen peroxide-induced hippocampal neurotoxicity.

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Ishii M, Iizuka R, Kiuchi Y, Mori Y, Shimizu S

Neuroprotection by lomerizine, a prophylactic drug for migraine, against hydrogen peroxide-induced hippocampal neurotoxicity.

Mol Cell Biochem. 2011 Dec;358(1-2):1-11. doi: 10.1007/s11010-011-0913-3. Epub 2011 Jun 9.

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21656126 [ View in PubMed
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Abstract

Migraine is one of the risk factor for ischemic stroke. The purpose of this study was to examine the effect of lomerizine, a prophylactic drug for migraine, on H(2)O(2)-induced cell death of hippocampal neurons. Cytosolic Ca(2+) concentration was measured using fura-2 as a Ca(2+) indicator. Cell death was estimated by trypan blue exclusion. In rat-cultured hippocampal neurons, the addition of H(2)O(2) induced biphasic Ca(2+) elevations and cell death. The H(2)O(2)-induced biphasic Ca(2+) elevations and cell death only occurred when extracellular Ca(2+) was present. The biphasic Ca(2+) elevation was mediated by Ca(2+) influx through the plasma membrane, but not Ca(2+) release from the intracellular Ca(2+) store. Both the early and late phases of H(2)O(2)-induced Ca(2+) influx were reduced by either a T- or L-type voltage-dependent Ca(2+) channel (VDCC) blocker, lomerizine. In fact, L-type VDCC (alpha(1C) subunit) and T-type VDCC (alpha(1G) subunit) mRNA were expressed in rat hippocampal neurons. Although an L-type VDCC blocker, nifedipine, partly suppressed the late phase of Ca(2+) influx in response to H(2)O(2), a T-type VDCC blocker, mibefradil, reduced both phases of Ca(2+) influx. Moreover, lomerizine and mibefradil strongly reduced H(2)O(2)-induced cell death, and nifedipine weakly reduced it. These findings suggest that the inhibition of H(2)O(2)-induced Ca(2+) influx through T-type VDCC seems to be important in the protective effect of lomerizine against oxidative stress. It is possible that lomerizine may be a useful drug for prophylactic treatment of migraine, because migraine is a risk factor for ischemic stroke.

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