Abstract

BackgroundIncreased systemic cytokines and elevated brain levels of monoamines, and hydroxyl radical productions are thought to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke. Dexamethasone (DXM) is a known immunosuppressive drug used in controlling inflammation, and hydroxyethyl starch (HES) is used as a volume-expanding drug in cerebral ischemia and/or cerebral injury. Acute treatment with a combined therapeutic approach has been repeatedly advocated in cerebral ischemia experiments. The aim of this study is to investigate whether the combined agent (HES and DXM) has beneficial efficacy to improve the survival time (ST) and heat stroke-induced cerebral ischemia and neuronal damage in experimental heat stroke.MethodsUrethane-anesthetized rats underwent instrumentation for the measurement of colonic temperature, mean arterial pressure (MAP), local striatal cerebral blood flow (CBF), heart rate, and neuronal damage score. The rats were exposed to an ambient temperature (43 degrees centigrade) to induce heat stroke. Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.ResultsAfter heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats. However, immediate treatment with the combined agent at the onset of heat stroke confers significant protection against heat stroke-induced circulatory shock, systemic inflammation; cerebral ischemia, cerebral monoamines and hydroxyl radical production overload, and improves neuronal damage and the ST in rats.ConclusionsOur results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

Highlights

  • Increased systemic cytokines and elevated brain levels of monoamines, and hydroxyl radical productions are thought to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke

  • We propose whether application of the combined agent immediate treatment has efficacy to elongate the survival time, and improve the heat strokeinduced circulatory shock, cerebral ischemia, and neuronal damage in rats

  • The combined agent (DXM+hydroxyethyl starch (HES)) improves survival time in heat stroke Table 1 summarizes the effects of heat exposure (42°C Ta for 80 min) on survival time in rat heat stroke

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Summary

Introduction

Increased systemic cytokines and elevated brain levels of monoamines, and hydroxyl radical productions are thought to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke. In the rodents heat stroke model, significant decrements in both mean arterial pressure (MAP) and cerebral blood flow (CBF), but increments of cerebral monoamines levels, free radical productions and systemic cytokine levels are obtained in urethane-anaesthetized rats after heat stroke [8,9]. These pathophysiological changes are known to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke in rats [10]. High levels of cytokines and radicals in the peripheral blood stream, as well as excessive accumulation of glutamate, hydroxyl radicals, dopamine (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 [6,9,13,14]

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