Leuprolide Acetate Promotes Sensory Recovery and Modulates Dorsal Root Ganglion Responses After Sciatic Nerve Transection in Rats

TL;DR

Leuprolide acetate helps recover cold sensitivity and supports nerve healing after sciatic nerve injury in rats.

Contribution

LA's novel role in promoting sensory recovery and modulating DRG responses after nerve injury is demonstrated.

Findings

LA promotes recovery of cold sensitivity after sciatic nerve injury.

LA improves retrograde axonal transport and reduces inflammation in dorsal root ganglia.

LA modulates pro-regenerative gene expression in peripheral nerve injury.

Abstract

What are the main findings?
•LA promotes selective recovery of cold sensitivity after sciatic nerve transection.•LA enhances retrograde axonal transport after sciatic nerve transection.•LA attenuates reactive gliosis and macrophage activation in dorsal root ganglia after sciatic nerve transection.•LA modulates the expression of key pro-regenerative genes in peripheral nerve injury.

LA promotes selective recovery of cold sensitivity after sciatic nerve transection.

LA enhances retrograde axonal transport after sciatic nerve transection.

LA attenuates reactive gliosis and macrophage activation in dorsal root ganglia after sciatic nerve transection.

LA modulates the expression of key pro-regenerative genes in peripheral nerve injury.

What is the implication of the main finding?
•The results suggest that LA could be a promising therapeutic strategy to improve sensory recovery and neuroregeneration following peripheral nerve injury.

The results suggest that LA could be a promising therapeutic strategy to improve sensory recovery and neuroregeneration following peripheral nerve injury.

Background/Objectives: Sciatic nerve injuries are among the most common classes of peripheral nerve harm and have a strong impact on quality of life, as well as a significant negative economic impact for patients, society, and governments, since they represent a frequent cause of work-related disabilities and sick leave applications. Following nerve injury, neurons, Schwann, and satellite cells undergo marked changes in phenotype, metabolic activity, neuronal survival, nervous transmission, and an exacerbated activation of the inflammatory response. Leuprolide acetate (LA), a clinically available agonist of gonadotropin-releasing hormone (GnRH), has shown clear neurotrophic properties and is considered a novel potential candidate for treating neural injuries, including sciatic nerve pathologies. This study aimed to analyze the effect of LA treatment on sensory function and dorsal root ganglia (DRG) changes in a rat sciatic nerve full-transection (SNT) model. Methods: Variations in cold and heat sensitivity were assessed using the thermal plate test, while DRG tissue sections were examined for modifications in reactive gliosis by immunofluorescence analysis, and axonal transport using a retrograde tracer. Also, changes in the expression of pro-regenerative genes Stat3, Socs3, Fos, Jun, Atf4, and Limk1 were quantified by qPCR. Results: Our results showed that LA treatment exerted a distinct neurotrophic effect, since it promoted the specific recovery of cold sensitivity, improved axonal transport, regulated the inflammatory response, and modulated the exacerbated expression of pro-regenerative genes in the SNT model. Conclusions: These findings indicate that LA therapy may have the potential to improve sensory recovery in patients with sciatic nerve injuries.

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