Role of neurochemicals in brain edema and cell changes following hyperthermic brain injury in the rat.

The involvement of three potent neurochemical mediators of the edema formation such as serotonin, prostaglandins and opioids in the pathophysiology of hyperthermic brain injury was examined in a rat model using a pharmacological approach. Hyperthermic brain injury was induced in conscious young rats by exposing them to heat stress at 38 degrees C for 4 h. In these rats the blood-brain barrier (BBB) permeability, brain edema, cerebral blood flow (CBF), heat shock protein 72 kD (HSP) response and cell changes were examined. Pretreatment with ketanserin (a serotonin-2 receptor antagonist), indomethacin (prostaglandin synthesis inhibitor) and naloxone (opioid receptor antagonist) in separate groups of rats reduced hyperthermia and HSP response following heat stress and significantly attenuated changes in the BBB permeability, brain edema, CBF and cell reaction. These results suggest that the pathophysiology of hyperthermic brain injury is a complex mechanisms and several neurochemicals are involved in the brain pathology caused by heat stress.