SARM1 Inhibition Maintains Axonal Integrity After Rat Sciatic Nerve Transection and Repair.

Area of Science:

• Neuroscience
• Regenerative Medicine

Background:

• Sterile alpha and TlR motif containing-1 (SARM1) protein is crucial for initiating Wallerian degeneration after nerve injury.
• Understanding SARM1's role is key to developing strategies for nerve repair and functional recovery.

Purpose of the Study:

• To investigate if inhibiting SARM1 activity can prevent Wallerian degeneration.
• To assess the potential of SARM1 blockade for promoting faster axonal function recovery after nerve transection and repair.

Main Methods:

• A dominant-negative SARM1 (SARM1-DN) phenotype was induced in rats via adeno-associated virus injection.
• Rats underwent sciatic nerve transection and repair, followed by functional and electrophysiological assessments at various time points.
• Histomorphologic and electrodiagnostic studies were analyzed to evaluate nerve regeneration and function.

Main Results:

• SARM1 inhibition led to maintained axons and improved compound nerve action potential amplitude at 2 weeks post-injury.
• Muscle strength, specifically gastrocnemius strength, was enhanced in SARM1-DN rats at early time points (2 days and 2 weeks).

Conclusions:

• Inhibiting SARM1 promotes early axonal regeneration and myelination, enhancing action potential after nerve injury.
• SARM1 blockade shows potential for delaying Wallerian degeneration and accelerating functional motor recovery after nerve transection.