[Factors influencing nerve regeneration]

This paper describes the most important cellular and molecular factors that influence nerve regeneration. The first prerequisite for axonal regeneration is survival of the neuron. This depends on neuron type, age, and the degree and proximity of the injury to the cell body. Spinal motoneurons are less susceptible to injury-induced death than cranial motoneurons and sensory neurons. The surviving neurons undergo changes characteristic of a switch from a transmitting mode to a growing mode. They produce various neurotrophic factors and their receptors influencing the neuron and the non-neuronal cells such as Schwann cells. The distal nerve stump undergoes degenerative processes including removal of axons and phagocytosis of myelin debris, the so-called Wallerian degeneration. Until the second day phagocytosis is done by Schwann cells, hematogenous macrophages invade the distal stump at the second day and phagocyte the whole debris within two weeks. Devoid of axonal contact, the myelinating Schwann cells switch their function from myelination to growth support for the regenerating axons, including cell proliferation, downregulation of myelin components and upregulation of neurotrophic factors. Additionally, the Schwann cells form the so-called Bands of Büngner, cell columns serving as pathway for the growing axon. Trophic factors, cell adhesion molecules and extracellular matrix influence the neuron, the growing axon and the endorgan as well as the non-neuronal cells such as Schwann cells, fibroblasts and macrophages. Application of drugs or trophic substances to enhance nerve regeneration after trauma and reconstruction is in the very beginning, and thus requires further experimental and clinical studies. Experimentally, FK 506 was found to support axonal regeneration after crush lesions and nerve grafting. Growth factors are currently administered clinically in other neurological diseases.