Energetic metabolism in mouse cerebral cortex during chronic hypoxia.

We measured the activities of Na(+)K(+) ATPase and of enzymes of the glycolytic pathway, Krebs cycle, and the respiratory chain in cerebral cortex of mice exposed to chronic hypoxia for three weeks and compared their values with those of sea level controls. There were no differences in Na(+)K(+) ATPase activity or in the activity of glycolytic enzymes. In the Krebs cycle, a 66% increase of succinate dehydrogenase activity was found due to a lower Km. In contrast, respiratory chain cytochrome oxidase activity was reduced by 12% in mice exposed to hypoxia. This suggested that the metabolic demand would be satisfied despite the respiratory chain depression (cytochrome oxidase), probably due to anaerobic energy production within the mitochondria (succinate dehydrogenase).

Increased brain capillaries in chronic hypoxia.

The effect of chronic hypobaric hypoxia (28 days, 455 Torr) on the organization of brain vessels was studied in Balb/c mice. In comparison to age-matched controls kept at sea level, emulsion-perfused capillaries in hypoxic mice showed marked dilation in all brain areas studied. Capillary length per unit volume of tissue (Lv) was increased in the cerebellar granular layer, the caudate nucleus, the globus pallidus, the substantia nigra, the superior colliculus, and the dentate gyrus. There was a selective increase of Lv in the hippocampus (CA1 strata pyramidale and lacunosum and CA3 strata pyramidale and oriens) and in somatosensory cortex layers V and VI, motor cortex layers II, III, V, and VI, and auditory cortex layers II and III. An increase in capillary surface area per unit volume of tissue was also determined in several brain areas, including layer IV of somatosensory cortex, where Lv was not significantly increased. The O2 diffusion conductance and PO2 in the tissues were estimated with a mathematical model. The remodeling of capillary diameter and length during chronic hypoxia accounts for the significant increase of O2 conductance to neural tissues. Also the estimated tissue PO2 in chronic brain hypoxia is markedly increased in the caudate nucleus and the substantia nigra compared with acute hypoxia. These results suggest that formation of new capillaries is an important mechanism to restore the O2 deficit in chronic brain hypoxia and that local rates of energy utilization may influence angiogenesis in different areas of the brain.