Neuroprotective effects of the agonist of metabotropic glutamate receptors ABHxD-I in two animal models of cerebral ischaemia

Dorota Makarewicz, Roman Gadamski, Apolonia Ziembowicz, Alan P. Kozikowski, Jarda T. Wroblewski, Jerzy W. Lazarewicz

Research output: Contribution to journalArticlepeer-review

Abstract

The neuroprotective efficacy of 2-aminobicyclo[2.1.1]hexane-2,5- dicarboxylic acid-I (ABHxD-I), a rigid agonist of metabotropic glutamate receptors, was studied using a 3-min global cerebral ischaemia model in Mongolian gerbils and the hypoxia/ischaemia model in 7-day-old rats. The effects on brain damage of ABHxD-I (30 mg/kg, intraperitoneally or 7.5 μg intracerebroventricularly) administered 30 min before global ischaemia or 30 min after hypoxia/ischaemia was evaluated 14 days after the insults. Treatment of adult gerbils with ABHxD-I injected i.c.v. but not systemically, prevented post-ischaemic hyperthermia and substantially reduced brain damage. These effects may reflect low permeability of the adult blood-brain barrier to ABHxD-I, and the role of reduced body and brain temperature in neuroprotection after its i.c.v. administration. ABHxD-I given either i.p. or i.c.v. to developing rats reduced brain damage by 55 and 37%, respectively, without affecting the body temperature. Due to immaturity and increased post-ischaemic permeability of the blood-brain barrier in developing rats, ABHxD-I may induce neuroprotection by direct interference with brain metabotropic glutamate receptors.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalResuscitation
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Agonist
  • Brain ischaemia
  • Glutamate
  • Hypoxia
  • Infant
  • Neurones

ASJC Scopus subject areas

  • Emergency Medicine
  • Emergency
  • Cardiology and Cardiovascular Medicine

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