Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury

Journal of Neuroinflammation

Matt S Ramer¹  Phillip G Popovich²  Andrew D Gaudet¹ 

[1] International Collaboration On Repair Discoveries (ICORD), Vancouver Coastal Health Research Institute, and Department of Zoology, University of British Columbia, 818 West 10th Ave, Vancouver, BC, V5T 1M9, Canada;Department of Neuroscience and Center for Brain and Spinal Cord Repair, College of Medicine, The Ohio State University, 770 Biomedical Research Tower, 460 West 12th Ave, Columbus, OH, 43210, USA

关键词: galectin-1;    spinal cord injury;    inflammation;    neuroinflammation;    phagocytosis;    Wallerian degeneration;    axotomy;    microglia;    Macrophage;   

Others  :  1213141
DOI  :  10.1186/1742-2094-8-110

 received in 2011-07-14, accepted in 2011-08-30,  发布年份 2011

【 摘 要 】

In this review, we first provide a brief historical perspective, discussing how peripheral nerve injury (PNI) may have caused World War I. We then consider the initiation, progression, and resolution of the cellular inflammatory response after PNI, before comparing the PNI inflammatory response with that induced by spinal cord injury (SCI).

In contrast with central nervous system (CNS) axons, those in the periphery have the remarkable ability to regenerate after injury. Nevertheless, peripheral nervous system (PNS) axon regrowth is hampered by nerve gaps created by injury. In addition, the growth-supportive milieu of PNS axons is not sustained over time, precluding long-distance regeneration. Therefore, studying PNI could be instructive for both improving PNS regeneration and recovery after CNS injury. In addition to requiring a robust regenerative response from the injured neuron itself, successful axon regeneration is dependent on the coordinated efforts of non-neuronal cells which release extracellular matrix molecules, cytokines, and growth factors that support axon regrowth. The inflammatory response is initiated by axonal disintegration in the distal nerve stump: this causes blood-nerve barrier permeabilization and activates nearby Schwann cells and resident macrophages via receptors sensitive to tissue damage. Denervated Schwann cells respond to injury by shedding myelin, proliferating, phagocytosing debris, and releasing cytokines that recruit blood-borne monocytes/macrophages. Macrophages take over the bulk of phagocytosis within days of PNI, before exiting the nerve by the circulation once remyelination has occurred. The efficacy of the PNS inflammatory response (although transient) stands in stark contrast with that of the CNS, where the response of nearby cells is associated with inhibitory scar formation, quiescence, and degeneration/apoptosis. Rather than efficiently removing debris before resolving the inflammatory response as in other tissues, macrophages infiltrating the CNS exacerbate cell death and damage by releasing toxic pro-inflammatory mediators over an extended period of time. Future research will help determine how to manipulate PNS and CNS inflammatory responses in order to improve tissue repair and functional recovery.

【 授权许可】

   
2011 Gaudet et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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Figure 3.

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