Nature of signals that initiate the immune response during Wallerian degeneration of peripheral nerves

Enhanced Repair Effect of Toll-Like Receptor 4 Activation on Neurotmesis: Assessment Using MR Neurography

“…Animals that received LPS injection had more pronounced gadofluorine enhancement and more prolonged T2 values of nerves on MR neurography during the degenerative phase, and achieved slightly higher SFIs and had faster myelin debris clearance and subsequently more pronounced axonal regeneration than those treated with PBS injection. In Wallerian degeneration following acute nerve injury, axonal degeneration products activate TLR pathway in Schwann cells, 15 then TLR signaling activation initiates the innate immune response and aids in subsequent macrophage recruitment, whereas acute neurodegeneration without any intervention would induce a shift in the TLR expression pattern of Schwann cells from normally high expression of TLR3 and TLR4 to strong expression of TLR1. 16 Further study also suggests that Wallerian degeneration in animals deficient in TLR2 or TLR4 showed impaired macrophage-mediated debris clearance and axon regeneration.…”

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

“…We explain these discrepancies between our study and theirs by the presence of Schwann cells in our model. Schwann cells in culture have been shown to express several TLRs, including TLR2, TLR3, and TLR4 (Karanth et al, 2006;Lee et al, 2006). They are also the main cellular source of MCP-1 for the first few hours after peripheral nerve injury (Taskinen and Roytta, 2000), a process that appears to be partially initiated by the stimulation of TLR4 on Schwann cells (Karanth et al, 2006).…”

“…In culture, Schwann cells treated with necrotic neuronal cells become activated and express proinflammatory genes through TLR2 and TLR3 pathways (Lee et al, 2006). Furthermore, Karanth et al (2006) have demonstrated that molecules derived from nerve homogenates induce MCP-1 expression in primary Schwann cells and that activity in nerve homogenates is partially inhibited by TLR4 functionblocking antibodies. Another study has recently shown that intact ECM inhibits TLR4 activation and that degradation of ECM by proteases not only relieves TLR4 inhibition but generates endogenous soluble agonists (e.g., heparan sulfate) that stimulate the receptor (Brunn et al, 2005).…”

Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease

“…Three recent papers provide evidence for the involvement of Toll-like receptor (TLR) signaling (Boivin et al, 2007;Karanth et al, 2006;Lee et al, 2006). Two of these studies presented in vitro evidence showing that products of degenerated neural tissue stimulate monocyte chemotactic protein-1 (MCP-1) [also designated chemokine (CÀ ÀC motif) ligand 2 (CCL2)] expression in Schwann cells partially via TLR2 and 3 (Lee et al, 2006) and TLR4 (Karanth et al, 2006). These findings were extended by in vivo work demonstrating that the expression of interleukin-1 beta (IL-1b) is reduced in the distal segment of the injured sciatic nerve in mice lacking TLR2, 4 and the adaptor protein myeloid differentiation primary response gene 88 (MyD88) at 24 h, while MCP-1 expression was reduced in mice lacking MyD88 at 1.5 h after injury but not in TLR2 or four deficient mice (Boivin et al, 2007).…”