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Stem cells reside in specialized microenvironments or 'niches' that regulate their function. In vitro studies using hypoxic culture conditions (<5% O2) have revealed strong regulatory links between O2 availability and functions of stem and precursor cells. Although some stem cells are perivascular, others may occupy hypoxic niches and be regulated by O2(More)
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1alpha, which accumulates under hypoxic conditions, and a constitutively expressed subunit HIF-1beta. In this study we analyzed HIF-1alpha expression in the rat cerebral cortex after(More)
Changes in cerebral blood volume due to augmented or diminished numbers of blood-perfused capillaries can be studied in small animals by optical methods. Capillary mean transit time was determined by detection of the passage of a hemodilution bolus through a region of the parietal cerebral cortical surface, using a reflectance spectrophotometer through a(More)
Hypoxia-inducible factor (HIF) prolyl 4-hydroxylases are a family of iron- and 2-oxoglutarate-dependent dioxygenases that negatively regulate the stability of several proteins that have established roles in adaptation to hypoxic or oxidative stress. These proteins include the transcriptional activators HIF-1alpha and HIF-2alpha. The ability of the(More)
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates adaptive responses to the lack of oxygen in mammalian cells. HIF-1 consists of two proteins, HIF-1alpha and HIF-1beta. HIF-1alpha accumulates under hypoxic conditions, whereas HIF-1beta is constitutively expressed. HIF-1alpha and HIF-1beta expression were measured during adaptation(More)
Diabetes is associated with extensive microvascular pathology and decreased expression of the glucose transporter (GLUT-1) in retina, but not brain. To explore the basis of these differences, the authors simultaneously measured glucose influx (micromol x g(-1) x min(-1)) and blood flow (mL x g(-1) x min(-1)) in retina and brain cortex of nondiabetic control(More)
Prolonged hypoxia causes several adaptive changes in systemic physiology and tissue metabolism. We studied the effects of hypobaric hypoxia on glucose transport at the blood-brain barrier (BBB) in the rat. We found that hypoxia increased the density of brain microvessels seen on immunocytochemical stains using an antibody to the glucose transporting protein(More)
The brain is entirely dependent on a continual supply of nutrients for the production of energy and the maintenance of function. Brain attack is a good example of a condition where the loss of blood flow and the consequent deprivation of nutrients can be devastating in terms of both structure and function. The unique metabolic characteristics of the brain(More)
Intracellular pH in the intact, normally perfused rat brain cortex was determined by rapid scanning reflectance spectrophotometry of Neutral Red. Neutral Red, a pH indicator dye, was administered intraperitoneally to rats. Reflectance spectra recorded from the exposed dural surface of 11 anesthetized rats were used to calculate an intracellular pH of 7.04(More)