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Effect of a new calcium entry blocker, NB-818, on delayed neuronal death in the ischemic gerbil hippocampus.

Abstract
The effect of NB-818, a new dihydropyridine calcium entry blocker, on delayed neuronal death (DND) in the hippocampal CA1 subfield of gerbils after 5 minutes of forebrain ischemia induced by bilateral carotid artery occlusion was examined. Gerbils were treated intraperitoneally with NB-818 (0.1-3 mg/kg) just after release of the occlusion. Four days after the ischemia, they were fixed by perfusing 10% buffered-formalin, and the neuronal cell density (NCD, cell/mm) in the CA1 subfield was estimated under microscopy. The average NCD in the ischemic control group was 43 +/- 10.8 cells/mm, whereas NB-818 (3 mg/kg) significantly ameliorated DND with an average NCD of 143 +/- 24.2 cells/mm (P less than 0.01). In addition, NB-818 (3 mg/kg) significantly inhibited DND at 1, 2 and 4 weeks after transient ischemia: the average NCD of the NB-818 and ischemic control groups were 80 +/- 9.4 (P less than 0.01) and 43 +/- 7.7 cells/mm, 92 +/- 13.7 (P less than 0.05) and 52 +/- 9.3 cells/mm, and 57 +/- 5.0 (P less than 0.01) and 43 +/- 12.4 cells/mm, respectively. In this experiment, NB-818 exhibited a protective effect on DND in the hippocampal CA1 subfield after transient forebrain ischemia, and its effect persisted for up to 4 weeks. These findings suggest that NB-818 may be useful for clinical treatment of neurological deficit after an ischemic insult.
AuthorsK Kamei, S Tsuchida, K Taguchi, M Nishikibe
JournalJapanese journal of pharmacology (Jpn J Pharmacol) Vol. 56 Issue 3 Pg. 279-86 (Jul 1991) ISSN: 0021-5198 [Print] Japan
PMID1895574 (Publication Type: Journal Article)
Chemical References
  • Calcium Channel Blockers
  • Dihydropyridines
  • Dizocilpine Maleate
  • NPK 1886
Topics
  • Animals
  • Brain Ischemia (pathology)
  • Calcium Channel Blockers (administration & dosage, pharmacology)
  • Cell Survival (drug effects)
  • Dihydropyridines (administration & dosage, pharmacology)
  • Dizocilpine Maleate (administration & dosage)
  • Gerbillinae
  • Hippocampus (blood supply, drug effects)
  • Histocytochemistry
  • Injections, Intraperitoneal
  • Male
  • Neurons (drug effects, pathology)

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