Neuroprotective effects of the agonist of metabotropic glutamate receptors ABHxD-I in two animal models of cerebral ischaemia.
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 microg 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.
Makarewicz
Dorota
D
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
Gadamski
Roman
R
Ziembowicz
Apolonia
A
Kozikowski
Alan P
AP
Wroblewski
Jarda T
JT
Lazarewicz
Jerzy W
JW
D000818:Animals; D001812:Blood-Brain Barrier; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use*; D003998:Dicarboxylic Acids / Q000627:therapeutic use*; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
C112101:2-aminobycyclo(2.1.1)hexane-2,5-dicarboxylic acid; D001643:Bridged Bicyclo Compounds; D003998:Dicarboxylic Acids; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate