[Frontiers in Bioscience S3, 857-868, June 1, 2011]

Mechanisms and consequences of microglial responses to peripheral axotomy

Hakan Aldskogius

Department of Neuroscience, Uppsala University Biomedical Center, P.O. Box 593, 751 24 Uppsala, Sweden

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Peripheral nerve axotomy
3.1. The neuron-glia network and the dynamic functions of brain and spinal cord
3.2. Neuronal responses to peripheral axon injury - implications for glial activation
3.3. Central responses to peripheral axotomy - general aspects
4. Motor neuron axotomy
4.1. Anatomical aspects on models of motor neuron axotomy
4.2. Cellular and molecular changes in axotomized motor neurons
4.3. Microglial responses to motor neuron axotomy
4.4. Functional consequences of microglial responses to motor neuron axotomy
4.4.1. Role of microglia for survival of axotomized motor neurons
4.4.2. Role of microglia for axon regeneration
4.4.3. Role of microglia for synapse removal
4.4.4. Role of microglia for astroglial reactivity
4.4.5. Role of microglia for lymphocyte infiltration
5. Sensory neuron axotomy
5.1. Anatomical aspects on sensory neuron axotomy
5.2. Cellular and molecular changes in axotomized sensory neurons
5.3. Microglial responses to sensory neuron axotomy and their functional consequences
6. Summary and perspectives
7. Acknowledgements
8. References

1. ABSTRACT

Microglia respond rapidly to injury of peripheral nerve axons (axotomy). This response is integrated into the responses of the injured neurons, i.e. processes for neuron survival, axon regeneration and restoration of target contact. The microglial response is also integrated in changes in presynaptic terminals on axotomized motor or autonomic neurons and in changes in the central terminals of peripherally axotomized sensory neurons. Microglia also has an established role in interacting with astrocytes to shape their response to peripheral axotomy. Axotomy models in mice have demonstrated a role for microglia in regulating the entry of lymphocytes into motor nuclei or sensory areas following peripheral axotomy. Whether this is a universal component of peripheral nerve injury remains to be determined. Under certain circumstances, microglia activated by axotomy are major contributors to CNS pathology, e.g. in models of neuropathic pain. However, the general roles played by microglia after peripheral nerve injury are still incompletely understood. Early proposals that the microglial reaction to peripheral nerve injury is preparatory for the eventuality of neuron degeneration may still have relevance.