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Requirement of myeloid cells for axon regeneration.

Publication Type:

Journal Article

Source:

J Neurosci, Volume 28, Issue 38, p.9363-76 (2008)

Keywords:

Animals, Antigens, CD11, Antiviral Agents, Cells, Cultured, Disease Models, Animal, Female, Ganciclovir, Graft Survival, Granulocytes, Growth Cones, Macrophages, Mice, Mice, Knockout, Mice, Transgenic, Monocytes, Motor Activity, Myeloid Cells, Nerve Regeneration, Recovery of Function, Sciatic Neuropathy, Thymidine Kinase, Tissue Transplantation

Abstract:

<p>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.</p>

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