PPBP [4-phenyl-1-(4-phenylbutyl) piperidine] decreases brain injury after transient focal ischemia in rats

  • Stroke. 1996 Nov;27(11):2120-3. doi: 10.1161/01.str.27.11.2120.
H Takahashi  1 ,  J R Kirsch ,  K Hashimoto ,  E D London ,  R C Koehler ,  R J Traystman
Affiliations
  • 1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287-4963, USA.
PMID: 8898825 DOI: 10.1161/01.str.27.11.2120
Abstract

Background and purpose: We tested the hypothesis that intravenous administration of the potent sigma-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 mumol/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 sigma-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, sigma-receptors may influence the progression of injury in ischemic border regions.

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