The neuropharmacological basis of heat intolerance and its treatment

Abstract

The heatstroke syndrome is characterized by marked hyperthermia, severe neurological abnormalities, multiple organ dysfunction, endotoxemia, and increased levels of cytokines in the peripheral blood stream. Rodents, when exposed to a high ambient temperature, displayed arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischemia, and cerebral neuronal damage after the onset of heatstroke. Both arterial hypotension and intracranial hypertension result in cessation of cerebral blood flow and lead to oxygen and nutrient deprivation and the initiation of a neurotoxic cascade of secondary mechanisms. The neurotoxic cascade involves overloading of dopamine, serotonin, glutamate, glycerol, nitric oxide, hydroxyl radicals, and/or cytokines. Thus, any measures which are able to restore blood supply and/or intervene the secondary neurotoxic cascades can be used to prevent and/or to treat ischemic neuronal damage in heatstroke.