Dose-optimized HILT promotes peripheral nerve repair through BMP4-Smad9-mediated inhibition of neuroinflammation and oxidative stress

TL;DR

This study shows that high-intensity laser therapy (HILT) can improve recovery after nerve injury by reducing inflammation and stress through a specific signaling pathway.

Contribution

The study identifies the BMP4-Smad9 pathway as a novel mechanism through which HILT promotes nerve repair.

Findings

HILT reduces nerve injury-induced inflammation and oxidative stress in rats.

The BMP4-Smad9 pathway is activated by HILT to support nerve repair.

HILT improves nerve function and prevents muscle atrophy after sciatic nerve injury.

Abstract

Evidence has shown that high-intensity laser therapy (HILT) may be beneficial for recovery after peripheral nerve injury (PNI). However, the optimized doses and effective mechanisms remain unclear. The present study sought to explore the effects of various doses of HILT on the recovery of nerve function in sciatic nerve injury (SNI) rats. The potential mechanism of action of HILT alleviating PNI was also assessed. Behavioral testing, polymerase chain reaction, immunoblotting, and immunofluorescence analyses were applied to explore whether HILT promotes the repair of injured nerves and its underlying mechanisms. SNI induces mechanical nociceptive hypersensitivity, disrupts sciatic nerve structure and function, causes gastrocnemius muscle atrophy, and increases oxidative stress and expression levels of inflammatory factors. HILT effectively ameliorated these SNI-induced alterations. Notably, the Bone Morphogenetic Protein 4 (BMP4)-SMAD Family Member 9 (Smad9) pathway mediates the therapeutic effects of HILT on SNI repair. These findings show for the first time that HILT stimulates the BMP4-Smad9 signaling pathway by increasing Smad9 expression to regulate inflammation and oxidative stress, which ultimately ameliorates SNI.

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