Achieving CNS axon regeneration by manipulating convergent neuro-immune signaling

John C. Gensel, Kristina A. Kigerl, Shweta S. Mandrekar-Colucci, Andrew D. Gaudet, Phillip G. Popovich

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations

Abstract

After central nervous system (CNS) trauma, axons have a low capacity for regeneration. Regeneration failure is associated with a muted regenerative response of the neuron itself, combined with a growth-inhibitory and cytotoxic post-injury environment. After spinal cord injury (SCI), resident and infiltrating immune cells (especially microglia/macrophages) contribute significantly to the growth-refractory milieu near the lesion. By targeting both the regenerative potential of the axon and the cytotoxic phenotype of microglia/macrophages, we may be able to improve CNS repair after SCI. In this review, we discuss molecules shown to impact CNS repair by affecting both immune cells and neurons. Specifically, we provide examples of pattern recognition receptors, integrins, cytokines/chemokines, nuclear receptors and galectins that could improve CNS repair. In many cases, signaling by these molecules is complex and may have contradictory effects on recovery depending on the cell types involved or the model studied. Despite this caveat, deciphering convergent signaling pathways on immune cells (which affect axon growth indirectly) and neurons (direct effects on axon growth) could improve repair and recovery after SCI. Future studies must continue to consider how regenerative therapies targeting neurons impact other cells in the pathological CNS. By identifying molecules that simultaneously improve axon regenerative capacity and drive the protective, growth-promoting phenotype of immune cells, we may discover SCI therapies that act synergistically to improve CNS repair and functional recovery.

Original languageEnglish
Pages (from-to)201-213
Number of pages13
JournalCell and Tissue Research
Volume349
Issue number1
DOIs
StatePublished - Jul 2012

Bibliographical note

Funding Information:
Acknowledgments This work was supported by the National Institute of Neurological Disorders and Stroke (NS047175 and NS072304), the Craig H. Neilsen Foundation (JCG & KAK), Canadian Institutes of Health Research (ADG) and the Ray W. Poppleton Endowment (PGP).

Keywords

  • DAMPs
  • Galectin-1
  • Inflammation
  • Neurotrauma
  • TLR

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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