Uninjured aged sympathetic neurons sprout in response to exogenous NGF in vivo

The extent to which the loss of plasticity by aged neurons is due to changes in the neuronal environment or to a loss of growth potential of the neurons has not been determined. In previous studies we observed that young adult cerebrovascular axons undergo a sprouting response following a 2-week intracerebroventricular infusion of nerve growth factor (15 μg; NGF). The present study used electron microscopy to examine the innervation of the intradural segment of the internal carotid artery of the aged rat and to determine whether aged sympathetic perivascular axons would respond to in vivo infusion of NGF. Young adult and aged Fischer 344 female rats received a 2-week intracranial infusion of NGF (15 μg) or vehicle (VEH) and were perfused for electron microscopy. Although there was no change in the total number of perivascular axons associated in aged VEH when compared with young adult VEH, a significant reduction was observed in aged VEH when total axons and sympathetic axons were expressed per μm2 vascular wall, reflecting an age-related increase in blood vessel size. Following NGF infusion, aged sympathetic axons were significantly increased by 192% compared with aged VEH cases. These results suggest that there is a proportional reduction in sympathetic cerebrovascular neurons with aging but that they exhibit robust sprouting in response to an exogenous neurotrophin.