Growth of Central NA Fibres Into Chronically Denervated Irides

Abstract

During regeneration in the peripheral nervous system it is well established that the neural sheaths play an active role in the stimulation and guidance of the regrowing axonal sprouts towards their denervated targets (see e.g. Cajal, 1928a; Weiss, 1941; Speidel, 1964). The attracting and organizing influences exerted by the iris transplants on the regrowth of lesioned central NA axons imply an interaction between the sprouting central fibres and elements within the adrenergically denervated peripheral tissue. One possible basis for such a mechanism, is that the neural elements, during the acute phases of the degeneration, would actively stimulate the axonal outgrowth, possibly through the release of an active principle from the acutely denervated tissue, as suggested by, i.a., Tello (1911) in his early studies on the sprouting of lesioned central axons into cortical implants of pieces of degenerating peripheral nerve (see also Hoffman, 1952; Edds, 1953). Such a possible mechanism seemed of particular interest in the regeneration of central NA neurons in view of the possible role of the so-called Nerve Growth Factor (NGF) proteins in the sprouting and regrowth of these neurons into hides transplanted to the CNS (Björklund and Stenevi, 1972; Bjerre et al., 1973, 1974; Stenevi et al., 1974; for review, see Björklund et al., 1974). Johnson et al. (1972) in fact reported that the release of endogeneous NGF from the isolated iris in vitro decreases considerably after 2–4 days, which coincides with the acute phase of axonal degeneration in the tissue. The observations of Johnson et al. (1972) and Silberstein et al. (1971) suggest, moreover, that this releaseable NGF might stimulate the regrowth of lesioned adrenergic axons in vitro. The present experiments were therefore undertaken to test whether the attracting influences of the iris on the sprouting of lesioned central NA axons might be bound to such a mechanism operating in the acutely denervated target tissue.