NNC 55-0396, a T-type calcium channel blocker, protects against the brain injury induced by middle cerebral artery occlusion and reperfusion in mice

J Pharmacol Sci. 2019 Jun;140(2):193-196. doi: 10.1016/j.jphs.2019.02.002. Epub 2019 Feb 21.

Abstract

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.

Keywords: Ischemia-reperfusion; Middle cerebral artery occlusion; T-type calcium channel.

MeSH terms

  • Animals
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / metabolism
  • Blood-Brain Barrier / metabolism
  • Brain Injuries / etiology*
  • Brain Injuries / prevention & control*
  • Calcium Channel Blockers / administration & dosage*
  • Calcium Channel Blockers / metabolism
  • Calcium Channels, T-Type / physiology
  • Cyclopropanes / administration & dosage*
  • Cyclopropanes / metabolism
  • Infarction, Middle Cerebral Artery / complications*
  • Infusions, Intraventricular
  • Infusions, Parenteral
  • Male
  • Mice, Inbred Strains
  • Naphthalenes / administration & dosage*
  • Naphthalenes / metabolism
  • Reperfusion Injury / complications*
  • Time Factors

Substances

  • Benzimidazoles
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Cyclopropanes
  • Naphthalenes
  • NNC 55-0396