nnc-55-0396 and Reperfusion-Injury

We tested whether NNC 55-0396 (NNC), a T-type calcium channel (T-channel) blocker, reduces the brain injury caused by middle cerebral artery occlusion and reperfusion (MCAO/R) in mice. NNC, administered i.c.v. before the occlusion, greatly reduced the MCAO/R-induced brain infarct and neurological dysfunctions, although it, given toward the end of occlusion, was less effective. Systemic administration of NNC before the occlusion also attenuated the infarct and neurological dysfunctions. Our data imply that blood-brain-barrier-permeable T-channel blockers such as NNC are capable of reducing MCAO/R-induced brain damage, and that T-channels are involved in neuronal damage induced by ischemia rather than reperfusion.

Topics: Animals; Benzimidazoles; Blood-Brain Barrier; Brain Injuries; Calcium Channel Blockers; Calcium Channels, T-Type; Cyclopropanes; Infarction, Middle Cerebral Artery; Infusions, Intraventricular; Infusions, Parenteral; Male; Mice, Inbred Strains; Naphthalenes; Reperfusion Injury; Time Factors