Impairment of toll-like receptors 2 and 4 leads to compensatory mechanisms after sciatic nerve axotomy

Peripheral nerve injury triggers responses in the damaged microenvironment, affecting the regenerative potential of neurons. Efficient clearance of myelin debris is crucial for nerve regeneration. Functional recovery depends on factors affected by the course of cellular and molecular events of Wallerian degeneration. This study investigated how the absence of functional TLR 2 and 4 affects nerve regeneration after peripheral nerve injury. Motor behavior was analyzed using a walking track test, focusing on paw pressure recovery related to muscle reinnervation and strength. The data reveals that the absence of functional TLR 4 gives an adaptive advantage in terms of muscle strength recovery. Lack of TLR 2, result in faster clearance of axon debris, contributing to a greater regenerated axon mean diameter following lesion.

• 1
  TLR4 mutant mice exhibited greater functional recovery and increased p75NTR and neurofilament protein expression compared to wild-type mice.
• 2
  TLR2 knockout mice showed a greater number of degenerated axons in the distal stump of the sciatic nerve and decreased p75NTR and neurofilament protein expression compared to the wild type.
• 3
  End-point equivalent functional recovery in TLR2 knockout mice may be due to enhanced axonal diameter found at 2 weeks after lesion, acting as a compensatory mechanism.