Hyperthermia is a means to influence many cellular systems which may prevent or increase the permeability of cell layers. In particular it may be used to increase the transport of drugs to the brain since this organ is well protected by various barriers including the blood-brain barrier (BBB). It functions as a physical, a metabolic and an immunological barrier. In this paper BBB barrier properties and permeability, the relation between stress and hyperthermia and the intracellular signalling pathways are shortly reviewed. More extensively, the artificial and pyrogenic induction of hyperthermia and the various effects of stress, particularly hyperthermia, on the heat-shock response, cytokines and ultimately on BBB permeability are reviewed. It is concluded that the effects of hyperthermia on BBB functionality are multitude and that the data in the literature on BBB permeability are rather diffuse and the results are influenced by many variations like species, dose, time, site, cells involved, stress stimuli, etc., which makes comparison difficult. The most important effectors of BBB permeability seem to be radical oxygen species (ROS), nitrogen monoxide (NO), peroxynitrite and pro-inflammatory cytokines, while heat-shock proteins (e.g. HSP70, HSP27) and heme-oxygenase (HSP32) play a protecting role.
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