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 polycy themia, increased brain vascularity, and increased density of the brai n capillary glucose transporter (GLUT-1). We now report on the time-co urse and reversibility of these adaptive alterations. Adult male Wista r rats were subjected to hypobaric hypoxia at 0.5 atmosphere for perio ds of 4 days or 1, 2 or 3 weeks, and compared to normoxic littermate c ontrols. Reversibility of the effects of hypoxia was studied in rats s ubjected 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 immunoc ytochemically stained with a GLUT-1 antibody. The density of GLUT-1 wa s determined in isolated cerebral microvessels by quantitative autorad iography of immunoblots. Blood hematocrit and cerebral microvascularit y did not significantly increase after 4 days of hypoxia, but were sig nificantly increased at 1, 2 and 3 weeks of hypoxia. Three weeks of no rmoxic recovery after 3 weeks of hypoxia reversed the polycythemia and cerebral hypervascularity. However, the density of GLUT-I in isolated cerebral microvessels, which was significantly increased after 1 and 3 weeks of hypoxia, remained elevated after 3 weeks of normoxia.