Hypothermia inhibits ischemia-induced efflux of amino acids and neuronal damage in the hippocampus of aged rats.
Brain hypothermia has been reported to protect against ischemic damages in adult animals. Our goal in this study was to examine whether brain hypothermia attenuates ischemic neuronal damages in the hippocampus of aged animals. We also determined effects of hypothermia on ischemia-induced releases of amino acids in the hippocampus. Temperature in the hippocampus of aged rats (19-23 months) was maintained at 36 degrees C (normothermia), 33 degrees C (mild hypothermia) or 30 degrees C (moderately hypothermia) using a thermoregulator during 20 min of transient forebrain ischemia. Cerebral ischemia increased extracellular concentrations of glutamate and aspartate by 6- and 5-fold, respectively, in the normothermic group. Mild and moderate hypothermia, however, markedly inhibited the rise of these amino acids to less than 2-fold. Elevation of extracellular taurine, a putative inhibitory amino acid, was 16-fold in the normothermic rats. Mild hypothermia attenuated ischemia-induced increase in taurine (10-fold), and moderate hypothermia inhibited the increase. Ischemic damages, evaluated by histopathological grading of hippocampal CA1 area 7 days after ischemia, was significantly ameliorated in the mild (1.3+/-0.5, mean+/-S.E.M.) and moderate hypothermic rats (0.8+/-0.3) compared with the normothermic ones (3.4+/-0.4). These results suggest that brain hypothermia protects against ischemic neuronal damages even in the aged animals, and the protection is associated with inhibition of excessive effluxes of both excitatory and inhibitory amino acids.
Ooboshi
H
H
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, 812-8582, Fukuoka, Japan. ooboshi@intmed2.med.kyushu-u.ac.jp
Ibayashi
S
S
Takano
K
K
Sadoshima
S
S
Kondo
A
A
Uchimura
H
H
Fujishima
M
M
D000375:Aging / Q000502:physiology*; D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000502:physiology; D018846:Excitatory Amino Acids / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007036:Hypothermia, Induced; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D018846:Excitatory Amino Acids; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000409:Alanine; D005998:Glycine