Cerebral adaptations to chronic anemia in a model of erythropoietin-deficient mice exposed to hypoxia

摘要

the mammalian brain is dependent on oxygen availability which is decreased in a hypoxic environment. Acute hypoxia induces an increase in cerebral blood flow (CBF) following cerebral vasodilation, partially mediated through nitric oxide (NO) and NO synthase (NOS) activity (21, 22). When hypoxia is prolonged, CBF slowly decreases and cerebrovascular adaptations take place such as an increased cerebral capillary density and a decrease in intercapillary distance, as described in the rat cerebral cortex (21,23, 24). All of these physiological adaptations are sustained by specific hypoxic molecular and cell signaling events. Hypoxia inducible factor (HIF-la) induces the activation of specific genes with a hypoxia responsive element, such as vascular endothelial growth factor (VEGF), inducible NO synthase isoform (iNOS), and erythro-poietin (Epo), which contribute to the physiological responses previously described (7, 25, 46). VEGF is an endothelial cell mitogen that has been implied in brain angiogenesis and increased vascular permeability following hypoxic exposure (20, 21, 45).