DECREASES IN CEREBRAL MICROVASCULATURE WITH AGE ARE ASSOCIATED WITH THE DECLINE IN GROWTH-HORMONE AND INSULIN-LIKE-GROWTH-FACTOR-1

Several reports have demonstrated that cerebral blood flow decreases w ith age and may contribute to neurodegenerative changes found in aging animals and man. Because GH and insulin-like growth factor 1 (IGF-1) decrease with age and have an important role in vascular maintenance a nd remodeling, we hypothesized that the decrease in cerebral blood flo w is associated with a rarefaction of cerebral blood vessels resulting from a decline in GH and IGF-1. Measurements of vascular density (num ber of vessels/cortical surface areal in both Brown-Norway and Fisher 344/Brown-Norway rats were made at 5, 13, and 29 months of age using c hronic cranial window chambers that allowed viewing of the cortical su rface and its corresponding vasculature. Correlations were made with p lasma levels of IGF-1. In Brown-Norway rats, arteriolar density decrea sed ii om 15.53 +/- 1.08 to 9.49 +/- 0.62 endpoints/mm(2) in 7- and 29 -month-old animals, respectively (P < 0.05). A decline was observed al so in arteriolar anastomoses [3.05 +/- 0.21 to 1.42 +/- 0.24 connectio ns/mm(2) in 7- and 29-month-old animals (P < 0.05)]. Venular density d id not decrease with age. Similar changes were observed in Fisher 344/ Brown-Norway rats. The number of cortical surface arterioles was corre lated with plasma IGF-1 levels at the time of vascular mapping (r = 0. 772, P < 0.05), and injection of bovine GH (0.25 mg/kg, sc, twice dail y for 35 days) to 30-month-old animals increased both plasma IGF-1 and the number of cortical arterioles. These data indicate that: 1) vascu lar density on the surface of the cortex decreases with age; 2) Vascul ar density is correlated with plasma levels of IGF-1; and 3) injection of GH increases cortical Vascular density in older animals. We conclu de that GH and IGF-1 have an important role in the decline in vascular density with age and suggest that decreases in vascular density may h ave important implications for the age-related decline in cerebral blo od flow and brain function.