Effect of a new calcium entry blocker, NB-818, on delayed neuronal death in the ischemic gerbil hippocampus.
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.
Kamei
K
K
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Tsuchida
S
S
Taguchi
K
K
Nishikibe
M
M
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects; D006651:Histocytochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016291:Dizocilpine Maleate; C048962:NPK 1886