Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Neurosci. 27 (46): 12565-12576

Copyright © 2007 by the Society for Neuroscience.


Toll-Like Receptor Signaling Is Critical for Wallerian Degeneration and Functional Recovery after Peripheral Nerve Injury

Audrey Boivin, Isabelle Pineau, Benoit Barrette, Mohammed Filali, Nicolas Vallières, Serge Rivest, , and Steve Lacroix

Laboratory of Molecular Endocrinology, CHUL Research Center, and Department of Anatomy and Physiology, Faculty of Medicine, Laval University, Ste-Foy, Québec, Canada G1V 4G2

Correspondence should be addressed to Dr. Steve Lacroix, CHUL Research Center and Laval University, 2705 Laurier Boulevard, Ste-Foy, Québec, Canada G1V 4G2. Email: Steve.Lacroix{at}

Abstract: Toll-like receptors (TLRs) bind specific components conserved among microorganisms as well as endogenous ligands produced by necrotic cells, injured axons, and the extracellular matrix. Here, we investigated whether TLRs are involved in regulating the immune response, Wallerian degeneration (WD), and nerve regeneration after sciatic nerve lesion. Early expression of interleukin-1ß and monocyte chemoattractant protein-1 was compromised in the sciatic nerve distal stump of mice deficient in TLR signaling. In addition, significantly fewer macrophages were recruited and/or activated in the sciatic nerve distal stump of TLR2-, TLR4-, and MyD88-deficient mice compared with wild-type littermates, whereas WD, axonal regeneration, and recovery of locomotor function were impaired. In contrast, animals that received a single microinjection of TLR2 and TLR4 ligands at the site of sciatic nerve lesion had faster clearance of the degenerating myelin and recovered earlier than saline-injected control rats. Finally, rats that had altered innate immune response through dexamethasone treatment exhibited three times more myelin debris in their sciatic nerve distal stump and a significant delay in recovery of locomotor function. Our results provide strong evidence that TLR signaling plays a critical role in orchestrating the innate immune response leading to efficient and rapid clearance of inhibitory myelin debris and nerve regeneration.

Key Words: sciatic nerve • macrophages • lipopolysaccharide • zymosan • myelin inhibitors • axonal regeneration

Received for publication July 3, 2007. Revision received Sept. 21, 2007. Accepted for publication Oct. 1, 2007.

Correspondence should be addressed to Dr. Steve Lacroix, CHUL Research Center and Laval University, 2705 Laurier Boulevard, Ste-Foy, Québec, Canada G1V 4G2. Email: Steve.Lacroix{at}

Beneficial Effects of {alpha}B-Crystallin in Spinal Cord Contusion Injury.
A. Klopstein, E. Santos-Nogueira, I. Francos-Quijorna, A. Redensek, S. David, X. Navarro, and R. Lopez-Vales (2012)
J. Neurosci. 32, 14478-14488
   Abstract »    Full Text »    PDF »
Non-surgical therapies for peripheral nerve injury.
P. Martinez de Albornoz, P. J. Delgado, F. Forriol, and N. Maffulli (2011)
Br. Med. Bull. 100, 73-100
   Abstract »    Full Text »    PDF »
Functional Recovery after Peripheral Nerve Injury is Dependent on the Pro-Inflammatory Cytokines IL-1{beta} and TNF: Implications for Neuropathic Pain.
S. Nadeau, M. Filali, J. Zhang, B. J. Kerr, S. Rivest, D. Soulet, Y. Iwakura, J. P. de Rivero Vaccari, R. W. Keane, and S. Lacroix (2011)
J. Neurosci. 31, 12533-12542
   Abstract »    Full Text »    PDF »
Reduced BACE1 Activity Enhances Clearance of Myelin Debris and Regeneration of Axons in the Injured Peripheral Nervous System.
M. H. Farah, B. H. Pan, P. N. Hoffman, D. Ferraris, T. Tsukamoto, T. Nguyen, P. C. Wong, D. L. Price, B. S. Slusher, and J. W. Griffin (2011)
J. Neurosci. 31, 5744-5754
   Abstract »    Full Text »    PDF »
TLR2 Hypersensitivity of Astrocytes as Functional Consequence of Previous Inflammatory Episodes.
A. Henn, S. Kirner, and M. Leist (2011)
J. Immunol. 186, 3237-3247
   Abstract »    Full Text »    PDF »
Regulation of the severity of neuroinflammation and demyelination by TLR-ASK1-p38 pathway.
X. Guo, C. Harada, K. Namekata, A. Matsuzawa, M. Camps, H. Ji, D. Swinnen, C. Jorand-Lebrun, M. Muzerelle, P.-A. Vitte, et al. (2010)
EMBO Mol Med. 2, 504-515
   Abstract »    Full Text »    PDF »
Microglial Toll-like Receptor 2 Contributes to Kainic Acid-induced Glial Activation and Hippocampal Neuronal Cell Death.
J. Hong, I.-H. Cho, K. Il Kwak, E. C. Suh, J. Seo, H. J. Min, S.-Y. Choi, C.-H. Kim, S. H. Park, E.-K. Jo, et al. (2010)
J. Biol. Chem. 285, 39447-39457
   Abstract »    Full Text »    PDF »
The interplay between the immune and central nervous systems in neuronal injury.
V. W. Yong and S. Marks (2010)
Neurology 74, S9-S16
   Abstract »    Full Text »    PDF »
Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice.
I. M. Chiu, H. Phatnani, M. Kuligowski, J. C. Tapia, M. A. Carrasco, M. Zhang, T. Maniatis, and M. C. Carroll (2009)
PNAS 106, 20960-20965
   Abstract »    Full Text »    PDF »
Signaling through MyD88 Regulates Leukocyte Recruitment after Brain Injury.
A. A. Babcock, H. Toft-Hansen, and T. Owens (2008)
J. Immunol. 181, 6481-6490
   Abstract »    Full Text »    PDF »
c-Jun is a negative regulator of myelination.
D. B. Parkinson, A. Bhaskaran, P. Arthur-Farraj, L. A. Noon, A. Woodhoo, A. C. Lloyd, M. L. Feltri, L. Wrabetz, A. Behrens, R. Mirsky, et al. (2008)
J. Cell Biol. 181, 625-637
   Abstract »    Full Text »    PDF »
Requirement of Myeloid Cells for Axon Regeneration.
B. Barrette, M.-A. Hebert, M. Filali, K. Lafortune, N. Vallieres, G. Gowing, J.-P. Julien, and S. Lacroix (2008)
J. Neurosci. 28, 9363-9376
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882