Delayed systemic administration of PACAP38 is neuroprotective in transient middle cerebral artery occlusion in the rat

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

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131 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1411-1417
Number of pages7
JournalStroke
Volume31
Issue number6
DOIs
StatePublished - Jun 2000

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Keywords

  • Cerebral infarction
  • Middle cerebral artery occlusion
  • Neuropeptides
  • Neuroprotection
  • Rats

ASJC Scopus subject areas

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

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