Time-course and reversibility of the hypoxia-induced alterations in cerebral vascularity and cerebral capillary glucose transporter density

The adult rat adapts to prolonged moderate hypobaric hypoxia by polycythemia, increased brain vascularity, and increased density of the brain capillary glucose transporter (GLUT-1). We now report on the time-course and reversibility of these adaptive alterations. Adult male Wistar rats were subjected to hypobaric hypoxia at 0.5 atmosphere for periods of 4 days or 1, 2 or 3 weeks, and compared to normoxic littermate controls. Reversibility of the effects of hypoxia was studied in rats subjected to hypobaric hypoxia for 3 weeks and then allowed to recover at normobaric conditions for 3 additional weeks. Cerebral vascularity was studied in cross-sections of the cerebral cortex that were immunocytochemically stained with a GLUT-1 antibody. The density of GLUT-1 was determined in isolated cerebral microvessels by quantitative autoradiography of immunoblots. Blood hematocrit and cerebral microvascularity did not significantly increase after 4 days of hypoxia, but were significantly increased at 1, 2 and 3 weeks of hypoxia. Three weeks of normoxic recovery after 3 weeks of hypoxia reversed the polycythemia and cerebral hypervascularity. However, the density of GLUT-1 in isolated cerebral microvessels, which was significantly increased after 1 and 3 weeks of hypoxia, remained elevated after 3 weeks of normoxia.