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

摘要

There is evidence that increased plasma cytokines, elevated brain levels of monoamines and hydroxyl radical production may be implicated in pathogenesis during heat stroke in rats. Acute treatment with a combined ther-apeutic approach has been repeatedly advocated in cerebral ischemia experiments. The aim of this study was to investigate whether the combined agent (mannitol and dexamethasone) has beneficial efficacy to improve the sur-vival time (ST) and heat stroke-induced damage in experimental heat stroke. Urethane-anesthetized rats under-went instrumentation for the measurement of colonic temperature, mean arterial pressure (MAP), striatal cere-bral blood flow (CBF), heart rate, and neuronal damage score. The rats were exposed to an ambient temperature (43 °C) to induce heat stroke. Concentrations of the ischemic and damage markers, dopamine, serotonin, and hy-droxyl radical production in corpus striatum, and the plasma levels of tumor necrosis factor-a (TNF-a) were ob-served during heat stroke. After the onset of heat stroke, the heat stroke rats display decreased MAP, decreased CBF, increased the plasma levels of TNF-a, increased cerebral striatal monoamines and hydroxyl radical pro-duction release, and severe cerebral ischemia and neuronal damage compared with those of normothermic con-trol rats. However, immediate treatment with the combined agent confers significant protection against heat stroke-induced arterial hypotension, systemic inflammation, cerebral ischemia, cerebral monoamines and hy-droxyl radical production overloads, and improves neuronal damage and the ST in heat stroke rats. Our data suggest that administration of this combined agent seems to have more effective to ameliorate the heat stroke-induced neuronal damage and prolong the ST.