Cerebrovascular dysfunction is an attractive target for therapy in heat stroke.

1. The aim of the present review is to summarize clinical observations and results of animal models that advance the knowledge of the attenuation of cerebrovascular dysfunction in the setting of heat stroke. It is a narrative review of selected published literature from Medline over the period 1959-2005. 2. All heat-stressed rodents, even under general anaesthesia, have hyperthermia, systemic inflammation, hypercoagulable state, arterial hypotension and tissue ischaemia and injury in multiple organs. These findings demonstrate that rodent heat stroke models can nearly mirror the full spectrum of human heat stroke. Experimental heat stroke fulfills the empirical triad used for the diagnosis of classical human heat stroke, namely hyperthermia, central nervous system alterations and a history of heat stress. 3. These physiological dysfunctions and survival during heat stroke can be improved by whole-body or brain cooling therapy adopted immediately after the onset of heat stroke. 4. However, in the absence of body or brain cooling, these heat stroke reactions can still be reduced by the following measures: (i) fluid replacement with 3% NaCl solution, 10% human albumin or hydroxyethyl starch; (ii) intravenous delivery of anti-inflammatory drugs, free radical scavengers or interleukin-1 receptor antagonists; (iii) hyperbaric oxygen therapy; or (iv) transplantation of human umbilical cord blood cells. 5. In addition, before initiation of heat stress, prior manipulations with one of the following measures was found to be able to protect against heat stroke reactions: (i) systemic delivery of alpha-tocopherol, mannitol, inducible nitric oxide synthase inhibitors, mu-opioid receptor antagonists, endothelin ETA receptor antagonists, serotoninergic nerve depletors or receptor antagonists, or glutamate receptor antagonists; or (ii) heat shock protein 72 preconditioning. 6. There is compelling evidence that cerebrovascular dysfunction is an attractive target for therapy in heat stroke.