Neuroprotective effect of mild hypothermia cannot be explained in terms of a reduction of glutamate release during ischemia.
An exogenous glutamate injection into the hypothermic hippocampal CA1 during 5-min ischemia produced the same extent of extracellular glutamate levels as observed in the normothermic CA1 during 5-min ischemia; however, neuronal death was not induced in the hypothermic CA1. Glutamate is released excessively into the extracellular space during ischemia, and is thought to induce brain injury by its neurotoxicity. It has been reported that the massive glutamate release is reduced by mild hypothermia, and it has been proposed that the reduction of ischemia-induced glutamate release exerts the neuroprotective effect on postischemic neuronal death. In the present study, to determine whether the neuroprotective effect of mild hypothermia on postischemic hippocampal CA1 neuronal death is due to the reduction of ischemia-induced glutamate release, gerbils were subjected to 5-min ischemia under hypothermic condition at 31 degrees C and were simultaneously injected exogenously with L-glutamate, so that the hypothermic CA1 around a microdialysis probe was exposed to the same extracellular glutamate levels as seen during normothermic ischemia, and the histological outcome was examined. An injection with 1 mM L-glutamate into the hypothermic CA1 during 5-min ischemia produced a similar extent of increased glutamate (17-fold increase) to that observed in the normothermic CA1 during 5-min ischemia (16-fold increase). However, neuronal death was not induced in the hypothermic CA1. This result indicates that the neuroprotective effect of mild hypothermia cannot be explained in terms of a reduction of glutamate release during ischemia.
Yamamoto
H
H
Department of Physiology, School of Medicine, Ehime University, Japan.
Mitani
A
A
Cui
Y
Y
Takechi
S
S
Irita
J
J
Suga
T
T
Arai
T
T
Kataoka
K
K
D000818:Animals; D005110:Extracellular Space / Q000502:physiology; D005849:Gerbillinae; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007036:Hypothermia, Induced; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D015424:Reperfusion; D012970:Sodium Glutamate / Q000494:pharmacology; D013997:Time Factors
D018698:Glutamic Acid; D012970:Sodium Glutamate