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Aging Reduces Hypoxia-Induced Microvascular Growth in the Rodent Hippocampus

¹ Program in Neuroscience and Departments of ² Neurobiology and Anatomy and ³ Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina.
⁴ Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Science Center, Oklahoma City.

Address correspondence to William Sonntag, PhD, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Science Center, 975 NE 10th Street, BRC-1303, Oklahoma City, OK 73104. E-mail: william-sonntag{at}ouhsc.edu

The effect of aging on microvascular density and plasticity in the rodent hippocampus, a brain region critically important for learning and memory, was investigated in F344xBN rats. Capillary density and angiogenesis were measured in three regions of the hippocampus in young and old rats and in old rats administered growth hormone, a treatment that improves cognitive function in older animals. Animals were housed under control conditions or in hypoxic conditions (11% ambient oxygen levels) to stimulate vascular growth. Our results indicate that aging is not associated with a reduction in hippocampal capillary density. However, aged animals demonstrate a significant impairment in hypoxia-induced capillary angiogenesis compared to young animals. Growth hormone treatment to aged animals for 6 weeks did not alter hippocampal capillary density and did not ameliorate the age-related deficit in angiogenesis. We conclude that aging significantly reduces hippocampal microvascular plasticity, which is not improved with growth hormone therapy.

Key Words: Rat—Hippocampus—Growth hormone—Capillary density—Angiogenesis