NEUROTROPHY AND REGENERATION IN-VIVO

Neural regeneration is a multistep event which appears to be controlle d by neurotrophic factors such as neurotrophins and/or neurotrophic cy tokines. Following traumatic, age- and/or disease-related responses, t hese molecules may be expressed and/or released by innervated target c ells, neuron-ensheathing glial cells, recruited macrophages or by the neural somata themselves which altogether provide possible cues for ne urotrophic strategies in vivo. in this respect, neurotrophic molecules may follow either paracrine, autocrine or even intracrine pathways in order to attenuate or even prevent neuronal degeneration. As neurotro phic molecules may have important functions as putative therapeutic ag ents for patients suffering from CNS disorders or from peripheral neur opathies, adequate and reliable animal lesion paradigms are of importa nce as in vivo assay systems. Axotomy models or selective neurotoxin-l esion models of anatomically well-defined neuron target connections ar e a first step towards assaying of neurotrophic actions in vivo. In le sioned central neural pathways, the existence of multineuronal network s, diffuse nuclear topography and a high degree of collateralization s hould be considered when studying regenerative potentials of trophic f actors. Because of their simple organization and accessibility, periph eral neural pathways are particularly appealing as assay systems. As n eurotrophic requirements and vulnerability vary among neural subsystem s, in vivo lesion paradigms reveal pharmacological rather than physiol ogical effects which have to be elucidated by more sophisticated exper imental paradigms and molecular tools.