PARTIAL CORTICAL DEVASCULARIZATION RESULTS IN ELEVATIONS OF CORTICAL NERVE GROWTH-FACTOR AND INCREASES NERVE GROWTH-FACTOR PROTEIN WITHIN BASAL FOREBRAIN CHOLINERGIC NEURONS

Previous studies have demonstrated that partial cortical devasculariza tion results in increased levels of nerve growth factor protein within the tissue immediately surrounding the infarcted region. In the prese nt study, we have used this lesion model to further characterize the n erve growth factor increase by investigating: (i) the time course for this phenomenon; (ii) the impact of the devascularizing lesion on cort ical regions not directly impinged upon by the lesion; and (iii) the r esponse of nerve growth factor-sensitive nucleus basalis neurons provi ding afferent cortical innervation to the increased availability of ne rve growth factor within their target territory. Our results indicate that, within the infarcted cortex, nerve growth factor levels increase rapidly following the lesion (up 51% by one day post lesion), reach a maximum of 136% above controls by three days and undergo a slow decli ne back to baseline levels by 23 days. Within the frontal and cingulat e cortices, which are not devascularized by the lesion and show no sig ns of pathological damage, nerve growth factor levels increase over a similar time course, and with a similar magnitude, to those in the les ioned cortex. Nerve growth factor-sensitive nucleus basalis neurons on the side ipsilateral to the lesion respond to increased cortical nerv e growth factor levels with an increased accumulation of nerve growth factor within :heir cell bodies (revealed by nerve growth factor immun ohistochemistry and quantitative enzyme-linked immunosorbent assay) wh ich was apparent at three days following the lesion, but no longer dis cernible at seven or 14 day or later. The present study investigated a model of cortical devascularization for its ability to alter nerve gr owth factor levels within the cortex. Nerve growth factor levels were rapidly increased within the infarcted cortical tissue beneath the les ion but were also elevated to a similar extent, ant with a similar tim e course, in cortical regions not directly impinged upon by the lesion . The retrograde impact of elevated cortical nerve growth factor level s was demonstrated by an increased accumulation of nerve growth factor within the cell bodies of nucleus basalis neurons providing innervati on to the cortez. This lesion model should provide a potential avenue for investigating the functional role(s) of nerve growth factor in the intact and lesioned adult central nervous system, as well as the inte rnal mechanisms-for regulating its synthesis, release, uptake, and deg radation. (C) 1998 IBRO. Published by Elsevier Science Ltd.