Role of Serotonin and Prostaglandins in Brain Edema Induced by Heat Stress. An Experimental Study in the Young Rat

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Abstract
The possibility that serotonin and prostaglandins participate in edema formation following heat stress (HS) was examined in young rats. Exposure of conscious young animals (8-9 weeks old) to heat at 38°C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%; wind velocity 20-25 cm/s) for 4 h resulted in marked increase in the whole brain water content (about 3%) as compared to animals kept at room temperature (21°C). A marked extravasation of Evans blue and 131I-sodium occurred in the brain of heat exposed animals as compared to normal animals. Morphological examination using electron microscopy of selected brain regions of heat stressed animals showed profound cell changes. Thus perivascular edema, swollen neuronal and glial cells, membrane damage, vesiculation of myelin, axonal swelling and synaptic damage was frequent in this group of untreated animals. Pretreatment with ketanserin (a selective serotonin2 receptor antagonist) or indomethacin (an inhibitor of prostaglandin synthesis) markedly reduced edema formation after 4 h HS in young animals. These heat stressed animals had considerably less extravasation of protein tracers as compared to the untreated group. Cell changes and edema at the ultrastructural level were mainly absent. Our results suggest that serotonin and prostaglandins are involved in heat stress induced breakdown of the BBB permeability, edema formation, and cell damage.