Journal
JOURNAL OF EXPERIMENTAL BIOLOGY
Volume 207, Issue 18, Pages 3163-3169Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jeb.00976
Keywords
hypoxia; rat brain; angiogenesis; capillary regression; apoptosis
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Funding
- NIGMS NIH HHS [GM066309] Funding Source: Medline
- NINDS NIH HHS [NS38632] Funding Source: Medline
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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.
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