| Abstract No.: | B-C2110 |
| Country: | Canada |
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| Title: | TOLL-LIKE RECEPTOR SIGNALING IS CRITICAL FOR WALLERIAN DEGENERATION AND FUNCTIONAL RECOVERY AFTER PERIPHERAL NERVE INJURY |
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| Authors/Affiliations: | 1 Isabelle Pineau*; 1 Nicolas Vallières; 1 Steve Lacroix;
1 Laval University and CHUL Research Center, Ste-Foy, QC, Canada
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| Content: | Toll-like receptors (TLRs) bind specific components conserved among microorganisms as well as endogenous ligands produced by necrotic cells, injured axons, and extracellular matrix. Here, we investigated whether TLRs are involved in regulating the immune response, Wallerian degeneration (WD), and nerve regeneration following sciatic nerve lesion. Early expression of IL-1β and MCP-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 to wild-type littermates, while 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. |
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