Effect of resuscitative mild hypothermia on glutamate and dopamine release, apoptosis and ischaemic brain damage in the endothelin-1 rat model for focal cerebral ischaemia.
The relationship between glutamate and dopamine release, apoptosis and ischaemic damage was studied following induction of transient focal cerebral ischaemia under normothermic (37 degrees C) and postischaemic (resuscitative) mild hypothermic (34 degrees C for 2 h) conditions in sevoflurane anaesthetized male Wistar rats. Focal ischaemia was induced by infusing endothelin-1 adjacent to the middle cerebral artery. In vivo microdialysis was used to sample glutamate and dopamine from striatum and parietal cortex of the ipsilateral hemisphere. The volume of ischaemic damage and the degree of apoptosis were determined 24 h after the insult. In both striatum and cortex of the normothermic group an initial increase in extracellular glutamate and dopamine levels following endothelin-1 infusion was observed. Striatal glutamate levels remained enhanced (250% of baseline) throughout the experiment, while the other neurotransmitter levels returned to baseline values. Hypothermia significantly attenuated the endothelin-1 induced glutamate release in the striatum. It also reduced apoptosis and infarct volume in the cortex. These results indicate that: (i) postischaemic mild hypothermia exerts its neuroprotective effect by inhibiting apoptosis in the ischaemic penumbral region; and (ii) this effect is not associated with an attenuation of glutamate or dopamine release in the cortex.
Van Hemelrijck
An
A
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels, Belgium.
Vermijlen
David
D
Hachimi-Idrissi
Said
S
Sarre
Sophie
S
Ebinger
Guy
G
Michotte
Yvette
Y
D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D019332:Endothelin-1; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D007036:Hypothermia, Induced / Q000379:methods; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1; D018698:Glutamic Acid; D004298:Dopamine