PPBP [4-phenyl-1-(4-phenylbutyl) piperidine] decreases brain injury after transient focal ischemia in rats.
OBJECTIVE
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.
Takahashi
H
H
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287-4963, USA.
Kirsch
J R
JR
Hashimoto
K
K
London
E D
ED
Koehler
R C
RC
Traystman
R J
RJ
D000818:Animals; D002544:Cerebral Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006220:Haloperidol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017480:Receptors, sigma / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D017480:Receptors, sigma; C094850:4-phenyl-1-(4-phenylbutyl)piperidine; D006220:Haloperidol