Structural and functional adaptation to hypoxia in the rat brain.
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.
LaManna
Joseph C
JC
Departments of Neurology and Anatomy, Case Medical School, Cleveland, OH 44106, USA. joseph.lamanna@case.edu
Chavez
Juan Carlos
JC
Pichiule
Paola
P
D000222:Adaptation, Physiological; D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002196:Capillaries / Q000502:physiology; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051381:Rats / Q000378:metabolism*; D012039:Regional Blood Flow
D010100:Oxygen