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- Title
Two structurally different T-type Ca<sup>2+</sup> channel inhibitors, mibefradil and pimozide, protect CA1 neurons from delayed death after global ischemia in rats.
- Authors
Bancila, M.; Copin, J.-C.; Daali, Y.; Schatlo, B.; Gasche, Y.; Bijlenga, Philippe
- Abstract
Recent in vitro evidence suggests that T-type Ca2+ channels are implicated in the mechanisms of ischemia-induced delayed neuronal cell death. The aim of this work was to study the neuroprotective potential of mibefradil and pimozide, both T-type Ca2+ channel inhibitors, in an in vivo rat model of global ischemia. Weperformed blinded and randomized placebo vs. treatment experiments using 57 animals to test mibefradil and fourteen animals to test pimozide. Each treated animal received a single stereotactic intraventricular injection of mibefradil or intraperitoneal injection of pimozide prior to transient global cerebral ischemia. Theprimary endpoint was the number of neurons surviving in the CA1 region 72 h after insult as evaluated by NeuN-labeled cell counts. All physiological variables monitored immediately before and after ischemic insult were equivalent between all groups. Surviving neurons in the CA1 region were significantly more frequent in the treated groups compared to the placebo group (mibefradil: 36.8 ± 2.8 cells in a 200 · 100 lm counting area vs. placebo: 25.2 ± 3.2 [P < 0.01]; pimozide: 39.4 ± 1.12 vs. placebo: 27.8 ± 0.7 [P < 0.0001]). Thus, administration of mibefradil or pimozide effectivelyprevents neuronal death after ischemia in a rat model of global ischemia. This study provides further support for a neuroprotective effect of T-typeCa2+ ocurrent inhibition during ischemia.
- Subjects
MIBEFRADIL (Drug); CELL death; ISCHEMIA; NEURONS; INTRAPERITONEAL injections; NEUROPROTECTIVE agents; LABORATORY rats
- Publication
Fundamental & Clinical Pharmacology, 2011, Vol 25, Issue 4, p469
- ISSN
0767-3981
- Publication type
Article
- DOI
10.1111/j.1472-8206.2010.00879.x