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(Stroke. 2000;31:1411.)
© 2000 American Heart Association, Inc.

Original Contributions

Delayed Systemic Administration of PACAP38 Is Neuroprotective in Transient Middle Cerebral Artery Occlusion in the Rat

Dora Reglodi, MD; Aniko Somogyvari-Vigh, MD; Sandor Vigh, MD; Tamas Kozicz, MD, PhD Akira Arimura, MD, PhD

From the Department of Medicine, Tulane University School of Medicine, New Orleans, and US-Japan Biomedical Research Laboratories, Tulane University Hebert Center, Belle Chasse, La.

Correspondence to Akira Arimura, MD, PhD, US-Japan Biomedical Research Laboratories, Tulane University Hebert Center, Building 30, 3705 Main St, Belle Chasse, LA 70037. E-mail arimura{at}mailhost.tcs.tulane.edu

Background and Purpose—Many substances have been shown to reduce brain damage in models of stroke, but mainly when given either before or shortly after the onset of ischemia. Delayed systemic administration of pituitary adenylate cyclase–activating polypeptide (PACAP) has been shown to attenuate the neuronal damage in the hippocampus in a model of global ischemia in rats. The present study examined the neuroprotective action of delayed systemic administration of PACAP38 in a model of transient focal ischemia produced by middle cerebral artery occlusion (MCAO) in rats.

Methods—We administered PACAP38 as an intravenous bolus (20 nmol/kg body wt) followed by an intravenous infusion for 48 hours using a micro-osmotic pump at a rate of 160 pmol/µL per hour, beginning 4, 8, or 12 hours after a 2-hour transient MCAO using a filament model. The size of the infarct was determined by examining 2-mm-thick brain sections stained with triphenyltetrazolium chloride, followed by image analysis. Control animals received intravenously 0.1% bovine serum albumin in 0.9% saline as a bolus and infusion at the same time intervals.

Results—The administration of PACAP38 beginning 4 hours after MCAO significantly reduced the infarct size by 50.88%. Treatment with PACAP38 starting 8 or 12 hours after the onset of ischemia did not result in a significant reduction of the infarct size, although infarct volumes tended to be smaller than in the control groups.

Conclusions—Systemic administration of PACAP38 should be clinically useful for reducing brain damage resulting from stroke even when administration is delayed for several hours.

Editorial Comment

Seth P. Finklestein, MD, Guest Editor

Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts

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