Faktoren, die die Regeneration peripherer Nerven beeinflussen[1]

Zusammenfassung

Ziel dieser Arbeit ist es, den derzeitigen Wissensstand über die wichtigsten zellulären und molekularen Faktoren darzulegen, die Einfluss auf die Regeneration peripherer Nerven haben. Die erste Voraussetzung für die Regeneration eines Axons nach einer Läsion ist das Überleben der Nervenzelle. Dies ist von der Art der Nervenzelle, ihrem Alter, der Art der Verletzung und der Entfernung der Verletzung vom Zellsoma abhängig. Spinale Motoneurone sind weniger anfällig für den verletzungsbedingten Zelltod als kraniale Motoneurone und sensible Nervenzellen. Bei der überlebenden Nervenzelle laufen verschiedene Veränderungen ab, die eine Wandlung vom ruhenden zum auswachsenden Neuron bezeichnen. Die verletzten Motoneurone produzieren verschiedene neurotrophische Faktoren und die dazugehörigen Rezeptoren, die sowohl auf das Neuron selbst wie auch auf die nicht neuronalen Zellen, in erster Linie die Schwannschen Zellen, wirken. Im distalen Nervenstumpf sind die Vorgänge zu Beginn degenerativ und beinhalten den Abbau der Axone und die Phagozytose des Myelins, die so genannte Wallersche Degeneration. In den ersten zwei Tagen der Wallerschen Degeneration ist die Einwanderung von Makrophagen minimal, so dass die Schwannschen Zellen den myelinalen Debris phagozytieren. Danach übernehmen dies hämatogene Makrophagen. Nach zwei Wochen ist die Wallersche Degeneration dann beendet. Mit dem Verlust des axonalen Kontaktes beginnt die myelinisierende Schwannsche Zelle innerhalb von zwei Tagen die Umstellung von der myelinisierenden zur regenerationsfördernden Zelle, d. h. es kommt zur Proliferation der Zellen, zur Ausbildung einer Zellsäule (Büngnersche Bänder) als Leitschiene für die regenerierenden Nervenfasern und zu einer verminderten Produktion der Substanzen, die zur Myelinisierung und Aufrechterhaltung des Myelins notwendig sind, während Wachstumsfaktoren, die bei intakten Nerven nur in geringem Maß produziert werden, vermehrt hergestellt und sezerniert werden. Die Expression vieler Moleküle, die entweder direkt oder über nicht-neuronale Zellen, wie Schwannsche Zellen, Makrophagen und Fibroblasten, Einfluss auf die axonale Regeneration haben, wird reguliert. Diese Substanzen können in neurotrophische Faktoren und Zelladhäsionsmoleküle unterteilt werden. Der therapeutische Einsatz von Pharmaka oder Wachstumsfaktoren in der Rekonstruktion peripherer Nerven befindet sich erst in den Anfängen und bedarf noch experimenteller und klinischer Versuche. In tierexperimentellen Studien zeigten eine Vielzahl von Wachstumsfaktoren eine regenerationsfördernde Potenz. Aber auch das Immunsuppressivum FK 506 verbesserte die Regeneration sowohl bei Kompressionsneuropathien als auch nach einer kompletten Nervendurchtrennung.

Abstract

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.

Nerven

Degeneration - Regeneration - Wachstumsfaktoren - Adhäsionsmoleküle - Therapieansätze

Nerves

degeneration - regeneration - growth factors - adhesion molecules - therapeutic approaches

1 Herrn o. Univ.-Prof. Dr. Wolfgang Schneider zum 60. Geburtstag gewidmet

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1 Herrn o. Univ.-Prof. Dr. Wolfgang Schneider zum 60. Geburtstag gewidmet