Neurotrophy and regeneration in vivo.

Neural regeneration is a multistep event which appears to be controlled by neurotrophic factors such as neurotrophins and/or neurotrophic cytokines. Following traumatic, age- and/or disease-related responses, these molecules may be expressed and/or released by innervated target cells, neuron-ensheathing glial cells, recruited macrophages or by the neural somata themselves which altogether provide possible cues for neurotrophic 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 neurotrophic molecules may have important functions as putative therapeutic agents for patients suffering from CNS disorders or from peripheral neuropathies, adequate and reliable animal lesion paradigms are of importance as in vivo assay systems. Axotomy models or selective neurotoxin-lesion models of anatomically well-defined neuron target connections are a first step towards assaying of neurotrophic actions in vivo. In lesioned central neural pathways, the existence of multineuronal networks, diffuse nuclear topography and a high degree of collateralization should be considered when studying regenerative potentials of trophic factors. Because of their simple organization and accessibility, peripheral neural pathways are particularly appealing as assay systems. As neurotrophic requirements and vulnerability vary among neural subsystems, in vivo lesion paradigms reveal pharmacological rather than physiological effects which have to be elucidated by more sophisticated experimental paradigms and molecular tools.