PPBP [4-phenyl-1-(4-phenylbutyl) piperidine], a potent σ-receptor ligand, decreases brain injury after transient focal ischemia in cats

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

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Background and Purpose: We tested the hypothesis that administration of 4- phenyl-1-(phenylbutyl) piperidine (PPBP), a potent σ-receptor ligand, during transient focal ischemia would affect early postischemic brain injury. Methods: Halothane-anesthetized cats underwent left middle cerebral artery occlusion for 90 minutes followed by 4 hours of reperfusion. Control cats received saline (n = 10). Experimental cats (2 groups, n = 10 per group) were treated with PPBP at a rate of 0.1 μmol/kg per hour (PPBP-0.1) or administered 1 μmol/kg per hour (PPBP-1) intravenously from 75 minutes after initiation of ischemia and continuing during the 4 hours of reperfusion. Results: As measured by the microsphere method, blood flow to the ipsilateral caudate nucleus was decreased similarly in all groups during ischemia. Blood flow to the ipsilateral inferior temporal cortex was decreased during ischemia in all groups but was higher in cats subsequently treated with PPBP at the highest dose, even before drug administration. There was no difference in blood flow to the ipsilateral caudate nucleus or inferior temporal cortex (area of greatest cortical injury) during reperfusion. Triphenyltetrazolium- determined injury volume of the ipsilateral cerebral hemisphere (control, 29±5%; PPBP-0.1, 17±3%; PPBP-1, 6±1% of ipsilateral hemisphere; mean±SEM) and caudate nucleus (control, 49±5%; PPBP-0.1, 39±6%; PPBP-1, 25±5% of ipsilateral caudate nucleus) was less in cats treated with 1 μmol/kg per hour of PPBP compared with cats treated with saline. Cats treated with 0.1 μmol/kg per hour had a 45% smaller hemispheric injury volume than the control group without differences in intraischemic blood flow. Recovery of somatosensory evoked potential amplitude was greater in cats treated with PPBP-1 compared with control (control, 18±11%; PPBP-0.1, 30±14%; PPBP-1, 54±14% of baseline). Conclusions: These data indicate that σ-receptors may play an important role in the mechanism of acute injury in both the cortex and the caudate nucleus after 90 minutes of transient focal ischemia in the cat. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, σ-receptors may contribute to the progression of injury in ischemic border regions.

Original languageEnglish (US)
Pages (from-to)1676-1682
Number of pages7
JournalStroke
Volume26
Issue number9
StatePublished - Sep 1995

Keywords

  • cerebral blood flow
  • evoked potentials, somatosensory
  • middle cerebral artery occlusion
  • sigma receptor
  • triphenyltetrazolium staining

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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