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First published online August 6, 2004
Journal of Experimental Biology 207, 3163-3169 (2004)
Published by The Company of Biologists 2004
doi: 10.1242/jeb.00976
Review Article |
Structural and functional adaptation to hypoxia in the rat brain
Departments of Neurology and Anatomy, Case Medical School, Cleveland, OH 44106, USA
* Author for correspondence (e-mail: joseph.lamanna{at}case.edu)
Accepted 12 March 2004
Chronic exposure to a hypoxic environment leads to structural and functional adaptations in the rat brain. One significant adaptation is a decrease in intercapillary distances through a near doubling of the capillary density, which begins after about 1 week of hypoxic exposure and is completed by 3 weeks. Hypoxic angiogenesis is controlled by activation of downstream genes by Hypoxia Inducible Factor-1 and Angiopoietin-2. The processes that increase capillary density are reversible upon restoration of the ambient oxygen concentration. Capillary regression, which also occurs over a 3-week period, is accomplished through activation of apoptosis. The implication from these observations is that the brain naturally functions in a low, but controlled, oxygen environment. Acute imbalances in oxygen delivery and metabolic demand are addressed through changes in blood flow; persistent imbalances activate mechanisms that adjust capillary density. The mechanisms that control these processes decline with age.
Key words: hypoxia, rat brain, angiogenesis, capillary regression, apoptosis
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