STRIATAL GLUTAMATE RELEASE IS IMPORTANT FOR DEVELOPMENT OF ISCHEMIC DAMAGE TO STRIATAL NEURONS DURING RAT HEATSTROKE

This study attempted to ascertain whether heatstroke-induced ischemia is associated with augmented striatal glutamate release and can be att enuated by NMDA receptor antagonists. Mean arterial pressure (MAP), st riatal cerebral blood flow (CBF), striatal glutamate release and stria tal neuronal damage score were assessed in saline-treated rats and in rats treated with NMDA receptor antagonists. Heatstroke was induced by exposing the animals to a high ambient temperature; the moment at whi ch MAP and CBF began to decrease from their peak levels was taken as t he onset of heatstroke. During onset of heatstroke, rats displayed hig her values of colonic temperature, striatal glutamate release and stri atal neuronal damage score, and lower values of MAP and striatal blood flow compared with normothermic control rats. The decreased MAP, the diminished striatal blood flow, the augmented striatal glutamate relea se and the increased striatal neuronal damage score during onset of he atstroke were significantly attenuated by pretreatment with an NMDA re ceptor antagonist such as MK-801 or ketamine. in addition, the surviva l time (interval between onset of heatstroke and death) of the rats wa s extended by pretreatment with one of these two NMDA receptor antagon ists. These results suggest that marked accumulation of glutamate in t he striatum is important for the development of ischemic damage to str iatal neurons during the onset of heatstroke. (C) 1998 Elsevier Scienc e B.V. All rights reserved.