Heat stress affects blood-brain barrier permeability to horseradish peroxidase in mice

The blood-brain barrier of mice subjected to hyperthermia for 0-135 min was examined using horseradish peroxidase (HRP) and Evans blue dye tracers by light, fluorescence and electron microscopy. Neither control nor heat-stressed mice exhibited extravasation of the Evans blue dye-albumin complex from the brain microvasculature. Gross examination of vibratome sections processed to reveal HRP reaction product exhibited multiple microfoci of HRP extravasation. Electron microscopic observations of the heat-stressed tissues revealed HRP reaction product within pinocytotic vesicles, tubulo-vesicular complexes, transendothelial channels and occasionally flooded within the cytoplasm of endothelial cells. HRP reaction product could clearly be seen in the basal laminae of the capillaries and in the surrounding neuropil. This study demonstrates that blood-brain barrier permeability to HRP is increased in response to heat stress and introduces a new, reproducible model of blood-brain barrier disruption.