This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuwaki, T. Articles by Nishimura, T. Search for Related Content PubMed PubMed Citation Articles by Kuwaki, T. Articles by Nishimura, T.

Stroke, Vol 20, 78-83, Copyright © 1989 by American Heart Association

ARTICLES

Nilvadipine attenuates ischemic degradation of gerbil brain cytoskeletal proteins

T Kuwaki, H Satoh, T Ono, F Shibayama, T Yamashita and T Nishimura
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.

We have previously demonstrated that transient cerebral ischemia induces marked decreases in concentrations of cytoskeletal proteins and have suggested putative involvement of calpain in the decrease of microtubule-associated protein 2 (MAP2) content. We examine the effect of nilvadipine, a new calcium channel blocker, on protein degradation in gerbil brains after 5 minutes of bilateral carotid artery occlusion and compare this effect with those of nimodipine and nicardipine. By densitometric quantification of the electrophoretically separated soluble proteins, mean +/- SEM MAP2 content in the hippocampus (14.4 +/- 1.8 micrograms/mg protein) was depleted (5.4 +/- 0.5 micrograms/mg, p less than 0.01) 4 days after ischemia; this depletion was significantly inhibited by 1 or 10 mg nilvadipine/kg/day. MAP2 content was also depleted in vitro when normal nonischemic brain extract was incubated with calcium, but this degradation was not inhibited by the calcium channel blockers. Our results suggest that calcium channel blockers do not act directly on calpain but act at the calcium channels of neurons and may suppress activation of the enzyme and attenuate ischemic degradation of cytoskeletal protein. We found nilvadipine to be the most potent drug among those studied, and we believe it could be useful for the treatment of cerebral ischemia.

This article has been cited by other articles:

				T. Wang, K. M. Raley-Susman, J. Wang, G. Chambers, J. E. Cottrell, I. S. Kass, and D. J. Cole Thiopental Attenuates Hypoxic Changes of Electrophysiology, Biochemistry, and Morphology in Rat Hippocampal Slice CA1 Pyramidal Cells • Editorial Comment Stroke, November 1, 1999; 30 (11): 2400 - 2407. [Abstract] [Full Text] [PDF]

				M. Kimura, K. Sawada, T. Miyagawa, M. Kuwada, K. Katayama, and Y. Nishizawa Role of Glutamate Receptors and Voltage-Dependent Calcium and Sodium Channels in the Extracellular Glutamate/Aspartate Accumulation and Subsequent Neuronal Injury Induced by Oxygen/Glucose Deprivation in Cultured Hippocampal Neurons J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 178 - 185. [Abstract] [Full Text]

				V. S. Miller Topical Review Article: Pharmacologic Management of Neonatal Cerebral Ischemia and Hemorrhage: Old and New Directions J Child Neurol, January 1, 1993; 8(1): 7 - 18. [Abstract] [PDF]