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(Stroke. 1996;27:2120-2123.)
© 1996 American Heart Association, Inc.

Articles

PPBP [4-Phenyl-1-(4-phenylbutyl) Piperidine] Decreases Brain Injury After Transient Focal Ischemia in Rats

Hiroshi Takahashi, MD; Jeffrey R. Kirsch, MD; Kenji Hashimoto, PhD; Edythe D. London, PhD; Raymond C. Koehler, PhD Richard J. Traystman, PhD

the Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions (H.T., J.R.K., R.C.K., R.J.T.), and the Neuroimaging and Drug Action Section, Division of Intramural Research, National Institute on Drug Abuse (K.H., E.D.L.), Baltimore, Md.

Background and Purpose We tested the hypothesis that intravenous administration of the potent -receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) during transient focal ischemia would decrease postischemic brain infarction volume in rats.

Methods Rats underwent intravascular focal ischemia for 2 hours followed by 22 hours of reperfusion. Halothane anesthesia was used only during initiation and cessation of ischemia. Rats received saline (n=10) or 1 µmol/kg per hour PPBP (n=10) by continuous intravenous infusion starting 1 hour after the initiation of ischemia and continuing through 22 hours of reperfusion.

Results There was no difference between groups in blood pressure, arterial blood gas values, and body temperature. Triphenyltetrazolium-determined infarction volume of ipsilateral cerebral cortex (saline, 39±6%; PPBP, 21±7% of ipsilateral hemisphere; mean±SEM) and striatum (saline, 68±6%; PPBP, 33±8% of ipsilateral striatum) was smaller in rats treated with PPBP than in rats treated with saline.

Conclusions These data indicate that -receptors may play an important role in the mechanism of injury both in cortex and striatum after 2 hours of transient focal ischemia in rats. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, -receptors may influence the progression of injury in ischemic border regions.

Editorial Comment

Paul G. Lysko, PhD, Guest Editor

Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa

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