Unless immediately recognized and treated, heat stroke is often lethal, and victims who do survive may sustain permanent neurological damage.1) The clinical diagnosis of heat stroke is demonstrated when hyperthermia is accompanied with circulatory shock (arterial hypotension), intracranial hypertension, and cerebral ischemia and injury. 2,3) Meanwhile, the heat stroke-induced central nervous system dysfunction includes delirium, convulsion, or coma. 4) Hence, prolonging survival time in heat stroke victims may offer more sufficient time for urgent treatment, thereby ameliorating the heat stroke-induced damage.Several lines of evidence indicate that rodents share with humans almost the same heat stroke syndromes, such as arterial hypotension, activated inflammation, and multiorgan dysfunction (in particular, cerebral ischemia, injury, and dysfunction. [5][6][7] 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 and free radical productions 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.10,11) Activated inflammation is evidenced by overproduction of pro-inflammatory cytokines (e.g., tumor necrosis factor-a (TNF-a)) in plasma of heat stroke rats.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. 19) Additionally, pretreatment with mannitol before the onset of heat stroke caused significant reduction of the heat strokeinduced the increased free radical formation and intracranial hypertension. 20) Although, many therapeutic agent show potential promise in many animal models, the results of most single-agent clinical trials are sobering. Consequently, various authors advocate studies to estimate the efficacy of combined therapeutic approaches. 21,22) Hence, the mannitol that acts to decrease intracranial pressure and radical formation, and a potent inflammatory agent (such as DXM) might be combined to develop an improved fluid therapy for attenuation or amelioration of heat stroke-induced damage. Furthermore, there is less attention to evaluate immediate effects of both DXM and mannitol (the combined agent) on heat stroke-induced pathophysiological changes, let alone their neuroprotective underlying influences, especially in the aspects...

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.

This study successfully demonstrated a significant cooling effect in rat brain by HRJVF. For preservation of brain function, HRJVF may be useful in resuscitation for trauma patients with hemorrhagic shock after further studies on animals with shock.