Effects of mild hypothermia on the cortical release of excitatory amino acids and nitric oxide synthesis following hypoxia.
Studies concerning neurotransmitter release following cerebral hypoxia are scarce, and the effects of mild hypothermia on hypoxia-induced neurotransmitter release are unknown. The purpose of this study was to investigate changes in excitatory amino acid (EAA) concentrations and nitric oxide (NO) synthesis following cerebral hypoxia in rats, and the effects of mild hypothermia on both. Cerebral hypoxia (PaO2, 30-40 mm Hg) was induced in each rat for 60 min. Cerebral blood flow (CBF) was measured by laser-Doppler flowmetry, and the extracellular concentrations of EAAs and NO end-products (nitrite and nitrate) were measured by in vivo microdialysis in normothermic (37 degrees C) and hypothermic (32 degrees C) rats. In both groups, CBF showed modest increases during hypoxia and returned to baseline during reoxygenation. The EAA levels of the normothermic rats increased markedly after hypoxia induction and returned to baseline levels during reoxygenation. Hypothermia abolished these increases completely. The NO end-product levels under normothermic conditions declined slightly during hypoxia, and then increased transiently during reoxygenation. Hypothermia appeared to attenuate the NO end-product level and to delay the peak. When the relationship between glutamate and the NO end-products was examined on an individual-animal basis, glutamate release did not parallel NO synthesis. The results indicate that hypothermic neuroprotection during cerebral hypoxia may be attributable to the amelioration of damage by reduction of presynaptic EAA release. Although it is unclear from the present results alone whether endothelial NO synthase, neuronal NO synthase or both caused the elevation of the NO end-products during reoxygenation, it is possible that the attenuation and delay of the peak of the NO end-product level plays a role in protection from NO-induced neuronal damage.
Fujisawa
H
H
Department of Neurosurgery, Yamaguchi University School of Medicine, Ube, Japan. fujisawa-ygc@umin.u-tokyo.ac.jp
Koizumi
H
H
Ito
H
H
Yamashita
K
K
Maekawa
T
T
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D018846:Excitatory Amino Acids / Q000378:metabolism*; D007035:Hypothermia / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018846:Excitatory Amino Acids; D009569:Nitric Oxide