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The Journal of Neuroscience, September 17, 2008, 28(38):9363-9376; doi:10.1523/JNEUROSCI.1447-08.2008

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Cellular/Molecular
Requirement of Myeloid Cells for Axon Regeneration

Benoit Barrette, Marc-André Hébert, Mohammed Filali, Kathleen Lafortune, Nicolas Vallières, Geneviève Gowing, Jean-Pierre Julien, and Steve Lacroix

Department of Anatomy and Physiology, Laval University, Ste-Foy, Québec, Canada G1V 4G2

Correspondence should be addressed to Dr. Steve Lacroix, Centre Hospitalier Université Laval Research Center and Laval University, 2705, Laurier Boulevard, Ste-Foy, Québec, Canada G1V 4G2. Email: steve.lacroix{at}crchul.ulaval.ca

The role of CD11b⁺ myeloid cells in axonal regeneration was assessed using axonal injury models and CD11b-TK^mt-30 mice expressing a mutated HSV-1 thymidine kinase (TK) gene regulated by the myeloid-specific CD11b promoter. Continuous delivery of ganciclovir at a sciatic nerve lesion site greatly decreased the number of granulocytes/inflammatory monocytes and macrophages in the distal stump of CD11b-TK^mt-30 mice. Axonal regeneration and locomotor function recovery were severely compromised in ganciclovir-treated CD11b-TK^mt-30 mice. This was caused by an unsuitable growth environment rather than an altered regeneration capacity of neurons. In absence of CD11b⁺ cells, the clearance of inhibitory myelin debris was prevented, neurotrophin synthesis was abolished, and blood vessel formation/maintenance was severely compromised in the sciatic nerve distal stump. Spinal cord-injured axons also failed to regenerate through peripheral nerve grafts in the absence of CD11b⁺ cells. Therefore, myeloid cells support axonal regeneration and functional recovery by creating a growth-permissive milieu for injured axons.

Key words: nervous system; macrophages; neurotrophins; sciatic nerve; spinal cord injury; angiogenesis

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Received April 4, 2008; revised July 21, 2008; accepted Aug. 10, 2008.

Correspondence should be addressed to Dr. Steve Lacroix, Centre Hospitalier Université Laval Research Center and Laval University, 2705, Laurier Boulevard, Ste-Foy, Québec, Canada G1V 4G2. Email: steve.lacroix{at}crchul.ulaval.ca

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