sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine affords neuroprotection from focal ischemia with prolonged reperfusion

I Harukuni; A Bhardwaj; A B Shaivitz; A C DeVries; E D London; P D Hurn; R J Traystman; Jeffrey R Kirsch; F M Faraci

doi:10.1161/01.STR.31.4.976

Back

sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine affords neuroprotection from focal ischemia with prolonged reperfusion

Journal article

Open access

Peer reviewed

sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine affords neuroprotection from focal ischemia with prolonged reperfusion

I Harukuni, A Bhardwaj, A B Shaivitz, A C DeVries, E D London, P D Hurn, R J Traystman, Jeffrey R Kirsch and F M Faraci

Stroke (1970), Vol.31(4), pp.976-981

04/2000

DOI: 10.1161/01.STR.31.4.976

PMID: 10754008

Files and links (1)

url

https://doi.org/10.1161/01.STR.31.4.976View

Published (Version of record) Open Access

Abstract

We previously showed that the intravenous administration of the potent final sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine (PPBP) provides neuroprotection against transient focal cerebral ischemia and that the protection depends on treatment duration. We tested the hypothesis that PPBP would provide neuroprotection in a model of transient focal ischemia and 7 days of reperfusion in the rat as assessed with neurobehavioral outcome and infarction volume. Under the controlled conditions of normoxia, normocarbia, and normothermia, halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) with the intraluminal suture occlusion technique. We used laser Doppler flowmetry to assess MCAO. At 60 minutes after the onset of ischemia, rats were randomly assigned to 1 of 4 treatment groups in a blinded fashion and received a continuous intravenous infusion of control saline or 0.1, 1, or 10 micromol. kg(-1). h(-1) PPBP for 24 hours. Neurobehavioral evaluation was performed at baseline (3 to 4 days before MCAO) and at 3 and 7 days of reperfusion. Infarction volume was assessed with triphenyltetrazolium chloride staining on day 7 of reperfusion in all rats. Triphenyltetrazolium chloride-determined infarction volume of ipsilateral cortex was smaller in rats treated with 10 micromol. kg(-1). h(-1) PPBP (n=15, 68+/-12 mm(3), 18+/-3% of contralateral structure, P<0.05) (mean+/-SEM) compared with corresponding rats treated with saline (n=15, 114+/-11 mm(3), 31+/-3% of contralateral structure). PPBP did not provide significant neuroprotection in the caudoputamen complex. Although MCAO was associated with several alterations in behavior, the treatment with PPBP had no effect on behavioral outcomes. The data demonstrate that the potent final sigma(1)-receptor ligand PPBP decreases cortical infarction volume without altering neurobehavior after transient focal ischemia and prolonged reperfusion in the rat.

Ligands

Brain Ischemia - complications

Neuroprotective Agents - therapeutic use

Drug Administration Schedule

Rats, Wistar

Reperfusion Injury - pathology

Haloperidol - analogs & derivatives

Haloperidol - administration & dosage

Haloperidol - therapeutic use

Rats

Male

Brain Ischemia - physiopathology

Animals

Brain Ischemia - drug therapy

Haloperidol - metabolism

Brain Ischemia - psychology

Cerebral Infarction - etiology

Behavior, Animal - drug effects

Receptors, sigma - metabolism

Cerebral Infarction - pathology

Details

Title: Subtitle: sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine affords neuroprotection from focal ischemia with prolonged reperfusion
Creators: I Harukuni - Departments of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4963, USA
A Bhardwaj
A B Shaivitz
A C DeVries
E D London
P D Hurn
R J Traystman
Jeffrey R Kirsch
F M Faraci
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.31(4), pp.976-981
DOI: 10.1161/01.STR.31.4.976
PMID: 10754008
NLM abbreviation: Stroke
ISSN: 0039-2499
eISSN: 1524-4628
Publisher: United States
Grant note: NS20020 / NINDS NIH HHS
Language: English
Date published: 04/2000
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040548702771

Metrics

10 Record Views

46 Times Cited - Web of Science