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 Yu, M. J. Articles by Clemens, J. A. Search for Related Content PubMed PubMed Citation Articles by Yu, M. J. Articles by Clemens, J. A.

Stroke, Vol 23, 1287-1291, Copyright © 1992 by American Heart Association

ARTICLES

A phenothiazine derivative reduces rat brain damage after global or focal ischemia

MJ Yu, JR McCowan, EB Smalstig, DR Bennett, ME Roush and JA Clemens
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Ind. 46285.

BACKGROUND AND PURPOSE: We previously reported that 2-(10H-phenothiazin- 2-yloxy)-N,N-dimethylethanamine hydrochloride is a potent inhibitor of iron-dependent lipid peroxidation in vitro and can protect primary cultures of rat hippocampal neurons from hydrogen peroxide-induced toxicity. Because oxidants may play an important role in mediating postischemic tissue injury, we evaluated this agent in two rat models of transient cerebral ischemia. METHODS: In a model of global forebrain ischemia, 23 male Wistar rats were subjected to 10 minutes of four- vessel occlusion followed by 72 hours of reperfusion. The rats received three intraperitoneal injections of either vehicle (2% aqueous acacia) or test agent (40 mg/kg). In a model of focal stroke, 19 spontaneously hypertensive rats were subjected to 2 hours of tandem middle cerebral and ipsilateral common carotid artery occlusion followed by 24 hours of reperfusion. The rats received three intraperitoneal injections of either vehicle (2% aqueous acacia) or test agent (40 mg/kg). RESULTS: In the global model, the phenothiazine significantly protected the CA1 layer of the hippocampus, with a reduction in mean damage score from 2.1 +/- 0.3 for control rats to 1.0 +/- 0.4 for treated rats (p less than 0.05). In the transient focal stroke model, the compound reduced cortical infarct volume from 130.1 +/- 10.3 mm3 for control rats to 95.2 +/- 24.5 mm3 for treated rats (p less than 0.02). CONCLUSIONS: Although the primary mechanism responsible for the protective effect is unclear at the present time, our study is consistent with the hypothesis that oxidant-mediated lipid peroxidation may be involved in the pathophysiology of postischemic brain injury.

This article has been cited by other articles:

				S. Kuroda, A. Nakai, T. Kristian, and B. K. Siesjo The Calmodulin Antagonist Trifluoperazine in Transient Focal Brain Ischemia in Rats : Anti-ischemic Effect and Therapeutic Window Stroke, December 1, 1997; 28(12): 2539 - 2544. [Abstract] [Full Text]