Effects of localized intracerebral injections of nerve growth factor on the regenerative growth of lesioned central noradrenergic neurones

In the adult rat, the growth of new axonal sprouts from lesioned central catecholamine and indolamine neurones into a denervated iris transplanted to the caudal diencephalon was previously shown to be markedly stimulated by an intraventricular injection of NGF. In the present study a similar stimulatory effect on the regrowth of lesioned central noradrenergic axons has been obtained with 100 times lower doses of the protein, injected locally into the brain tissue close to the cell bodies and axons of the locus coeruleus neurone system. The ingrowth of fibres into the transplant increased similarly when different parts of the noradrenergic neurones (i.e. the cell bodies or the proximal or distal parts of the surviving portions of the lesioned axons) were exposed to NGF, suggesting that the NGF sensitivity is not restricted to any specific part of the neurones. Moreover, experiments with iris transplants incubated in an NGF solution prior to the transplantation suggest a role for the NGF contained in the iris in the process of ‘reinnervation’ of the transplant by central noradrenaline neurones. The possibility of a difference in sensitivity to NGF between different central noradrenaline neurone systems, and between central noradrenaline, dopamine, and indolamine neurone systems is discussed. It was further clarified that the regenerating central neurones — similar to adult peripheral noradrenaline neurones — are most sensitive to the action of NGF during the very early stages of regeneration.