Heatstroke‐Induced Cerebral Ischemia and Neuronal Damage

Abstract

Experiments were carried out to ascertain whether the levels of brain monoamines and cytokines are involved in the heatstroke-induced cerebral ischemia and neuronal damage. Heatstroke was induced by exposing anesthetized rats to a high ambient temperature of 42 degrees C; the moment at which the mean arterial pressure began to decrease from its peak level was taken as the onset of heatstroke. It was found that, during the heatstroke-induced cerebral ischemia and neuronal damage, the extracellular concentration of either dopamine, serotonin or norepinephrine were increased in the hypothalamus, the corpus striatum and other brain regions. In addition, the concentration of interleukin-1 (IL-1), IL-6 and tumor necrosis factor in both the plasma and brain was also increased during heatstroke-induced cerebral ischemia and neuronal damage. Heatstroke-induced cerebral ischemia and neuronal damage were attenuated by depletion of brain dopamine or serotonin produced by intracerebral injection of 6-hydroxydopamine or 5,7-dihydroxytryptamine, respectively. Accordingly, the survival of these heatstroke rats was increased after brain dopamine or serotonin depletion. Furthermore, heatstroke-induced cerebral ischemia, neuronal damage and monoamine accumulation were attenuated by blockade of IL-1 receptor produced by treatment with an IL-1 receptor antagonist. The survival of the heatstroke rats was also increased after induction of heat shock protein. The results suggest that marked accumulation of either dopamine, serotonin or IL-1 in brain is important for the occurrence of heatstroke-induced cerebral ischemia and neuronal damage in rats. The survival of these heatstroke rats can be increased by inhibition of IL-1 receptors or monoamine system in brain as well as by induction of heat shock protein.

Prior Antagonism of Endothelin-1A Receptors Alleviates Circulatory Shock and Cerebral Ischemia During Rat Heatstroke

“…The plasma levels of TNF-a and IL-1b are shown to be well related to the severity of heatstroke (34,35). Indeed, increased levels of these cytokines are associated with heatstroke-induced arterial hypotension, cerebral ischemia, and neuronal damage (32,33; present results). Prior antagonism of ET A (present results) or IL-1b receptors (36,37) protects against heatstrokeinduced arterial hypotension, and cerebral ischemic damage and prolongs survival.…”

“…Our present and previous (32,33) results have shown that heatstroke induces systemic and central production of TNF-a and interleukin-1b (IL-1b ) in both rats and rabbits. The plasma levels of TNF-a and IL-1b are shown to be well related to the severity of heatstroke (34,35).…”

Effects of Combination Treatment with Dexamethasone and Mannitol on Neuronal Damage and Survival in Experimental Heat Stroke

“…22,35,36) There is evidence that cerebral ischemia (due to arterial hypotension and intracranial hypertension) may be one of the major causes to induce further damage after heat stroke onset. 14,19,37) After heat stroke induction, the CBF is instantly drops from highest peak, and it is concomitant with significant increments of cerebral ischemia and injury indexes, as shown in Fig. 1.…”

“…6,9,11,14,15) Various clinical and experimental investigations have shown that single doses of dexamethasone (DXM; exogenous glucocorticoids) or mannitol are extensively used in the treatment of cerebral ischemia and/or cerebral injury. [16][17][18] In the studies of heat stroke, pretreatment with DXM attenuated serum IL-1b levels and improved survival in heat stroke.…”

“…12,13) High levels of TNF-a in the peripheral blood stream, as well as excessive accumulation of glutamate, hydroxyl radicals, dopamome (DA) and serotonin (5-HT) in the central brain, correlate with the severity of circulatory shock, cerebral ischemia and neuronal damage during heat stroke in rats. 6,9,11,14,15) Various clinical and experimental investigations have shown that single doses of dexamethasone (DXM; exogenous glucocorticoids) or mannitol are extensively used in the treatment of cerebral ischemia and/or cerebral injury. [16][17][18] In the studies of heat stroke, pretreatment with DXM attenuated serum IL-1b levels and improved survival in heat stroke.…”