This Article Order Full text via Infotrieve Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Baskin, D. S. Articles by Schmidt, W. K. Search for Related Content PubMed PubMed Citation Articles by Baskin, D. S. Articles by Schmidt, W. K.

Stroke, Vol 25, 2047-2053, Copyright © 1994 by American Heart Association

ARTICLES

Evaluation of delayed treatment of focal cerebral ischemia with three selective kappa-opioid agonists in cats

DS Baskin, MA Widmayer, JL Browning, ML Heizer and WK Schmidt
Department of Surgery, Veterans Affairs Medical Center, Houston, Tex.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the therapeutic efficacy of three kappa-opioid agonists used for delayed treatment of experimental focal cerebral ischemia. METHODS: Forty halothane-anesthetized cats underwent permanent occlusion of the right intracranial internal carotid, middle cerebral, and anterior cerebral arteries via a transorbital, microsurgical approach. Six hours after occlusion, animals received a blinded bolus injection, and a subcutaneous osmotic pump was implanted to provide continuous release for 7 days. The injection and pump contained either saline or one of three kappa-agonists: dynorphin (1-13), U-50,488, or DuP E3800. Survival, neurological function, tissue damage, and brain weight were assessed. RESULTS: As a group, kappa-agonist-treated animals had higher survival (P < .02), less tissue damage (P < .02), and lower brain weight (P < .05) than saline controls. U-50,488 more effectively improved survival (P < .03) than dynorphin (P < .07) or E3800 (P < .07). Each of the three kappa compounds improved tissue damage (dynorphin, P < .02; U-50,488, P < .05; E3800, P < .05). Greater improvement in neurological function was seen after treatment with dynorphin (P < .05) than with U-50,488 (P < .6) or E3800 (P < .7). The only significant reduction in brain weight was seen after dynorphin treatment (P < .01). CONCLUSIONS: Compounds that act at the kappa subclass of opiate receptors are effective in increasing survival, improving neurological function, and decreasing tissue damage and edema in a cat model of focal cerebral ischemia. The current study provides support for the benefits of treatment of acute cerebrovascular ischemia with kappa-opioid agonists. The agents may prove to be of superior clinical utility because of efficacy even when administered 6 hours after the onset of stroke.

This article has been cited by other articles:

				B. Yulug, E. Cam, A. Yildiz, and E. Kilic Buprenorphine Does Not Aggrevate Ischemic Neuronal Injury in Experimental Focal Cerebral Ischemia J Neuropsychiatry Clin Neurosci, August 1, 2007; 19(3): 331 - 334. [Abstract] [Full Text] [PDF]

				C.-H. Chen, T. J.K. Toung, P. D. Hurn, R. C. Koehler, and A. Bhardwaj Ischemic Neuroprotection With Selective {kappa}-Opioid Receptor Agonist Is Gender Specific Stroke, July 1, 2005; 36(7): 1557 - 1561. [Abstract] [Full Text] [PDF]

				T.-Y. Chen, T. Goyagi, T. J.K. Toung, J. R. Kirsch, P. D. Hurn, R. C. Koehler, and A. Bhardwaj Prolonged Opportunity for Ischemic Neuroprotection with Selective {kappa}-Opioid Receptor Agonist in Rats Stroke, May 1, 2004; 35(5): 1180 - 1185. [Abstract] [Full Text] [PDF]

				Z. Zhang, T.-Y. Chen, J. R. Kirsch, T. J. K. Toung, R. J. Traystman, R. C. Koehler, P. D. Hurn, and A. Bhardwaj Kappa-Opioid Receptor Selectivity for Ischemic Neuroprotection with BRL 52537 in Rats Anesth. Analg., December 1, 2003; 97(6): 1776 - 1783. [Abstract] [Full Text] [PDF]

				T. Goyagi, T. J.K. Toung, J. R. Kirsch, R. J. Traystman, R. C. Koehler, P. D. Hurn, and A. Bhardwaj Neuroprotective {kappa}-Opioid Receptor Agonist BRL 52537 Attenuates Ischemia-Evoked Nitric Oxide Production In Vivo in Rats Stroke, June 1, 2003; 34(6): 1533 - 1538. [Abstract] [Full Text] [PDF]

				H. Boutin, F. Dauphin, E. T. MacKenzie, P. Jauzac, and R. C. Koehler Differential Time-Course Decreases in Nonselective, µ-, {delta}-, and {kappa}-Opioid Receptors After Focal Cerebral Ischemia in Mice • Editorial Comment Stroke, June 1, 1999; 30(6): 1271 - 1278. [Abstract] [Full Text] [PDF]

				C. G. a. C. Oberlander The Kappa Opioid Agonist Niravoline Decreases Brain Edema in the Mouse Middle Cerebral Artery Occlusion Model of Stroke J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 1 - 6. [Abstract] [Full Text]