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 hypother mia 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 rat s (19-23 months) was maintained at 36 degreesC (normothermia), 33 degreesC (mild hypothermia) or 30 degreesC (moderately hypothermia) using a thermore gulator during 20 min of transient forebrain ischemia. Cerebral ischemia in creased extracellular concentrations of glutamate and aspartate by 6- and 5 -fold, respectively, in the normothermic group. Mild and moderate hypotherm ia, however, markedly inhibited the rise of these amino acids to less than 2-fold. Elevation of extracellular taurine, a putative inhibitory amino aci d, was 16-fold in the normothermic rats. Mild hypothermia attenuated ischem ia-induced increase in taurine (10-fold), and moderate hypothermia inhibite d 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 result s 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. (C) 2 000 Elsevier Science BN. All rights reserved.