The duration of sprouted cerebrovascular axons following intracranial infusion of nerve growth factor

Abstract

We reported previously that a 2-week infusion of the trophic protein nerve growth factor (NGF) into the lateral ventricle of the adult rat brain elicits a sprouting response by perivascular axons associated with the intradural segment of the internal carotid artery. In the present study, we used electron microscopy to determine whether the sprouted axons persist following cessation of NGF delivery and, if not, to determine the time course of their disappearance. Our results demonstrate that NGF-induced sprouted axons do not persist following cessation of NGF delivery. The total number of axons at 1 week following the end of the NGF infusion was elevated compared to control values, but significantly reduced compared with NGF cases sacrificed immediately following the infusion period. Three weeks following the end of the NGF infusion, the total number of axons was similar to controls although there were no signs of axonal degeneration. These results suggest that continued elevation of NGF levels is necessary to maintain the sprouted axons and that endogenous levels of NGF, or other factors produced by the vascular target tissue, are not sufficient to maintain the newly formed axons. The demonstration that mature perivascular axons proliferate and disappear as a function of exogenous NGF exposure supports the accumulating evidence for continued plasticity in the mature nervous system.