Irisin Gene Delivery Ameliorates Burn-Induced Sensory and Motor Neuropathy.

Shu-Hung Huang,Shu-Hung Huang,Shih-Ming Yang,Sheng-Hua Wu,Sheng-Hua Wu,Sheng-Hua Wu,Jing-Jou Lo,Jing-Jou Lo,Ming-Hong Tai

doi:10.3390/ijms21207798

Abstract

Burn-related neuropathy is common and often involves pain, paresthesia, or muscle weakness. Irisin, an exercise-induced myokine after cleavage from its membrane precursor fibronectin type III domain-containing 5 (FNDC5), exhibits neuroprotective and anti-inflammatory activities. A rat model of third-degree burn on the right hind paw was used to investigate the therapeutic role of irisin/FNDC5. Rats received burn injury and were treated with intrathecal recombinant adenovirus containing the irisin sequence (Ad-irisin) at 3 weeks postburn. One week later, mechanical allodynia was examined. The expression of irisin in cerebrospinal fluid (CSF) was detected. Ipsilateral gastrocnemius muscle and lumbar spinal cord were also obtained for further investigation. Furthermore, the anti-apoptotic effect of recombinant irisin in SH-SY5Y cells was evaluated through tumor necrosis factor alpha (TNFα) stimulus to mimic burn injury. We noted intrathecal Ad-irisin attenuated pain sensitization and gastrocnemius muscle atrophy by modulating the level of irisin in CSF, and the expression of neuronal FNDC5/irisin and TNFα in the spinal cord. Ad-irisin also ameliorated neuronal apoptosis in both dorsal and ventral horns. Furthermore, recombinant irisin attenuated TNFα-induced SH-SY5Y cell apoptosis. In summary, irisin attenuated allodynia and muscle wasting by ameliorating neuroinflammation-induced neuronal apoptosis.

Highlights

Neuropathy following burn trauma is common and often undiagnosed [1,2,3]
To identify whether spinal expressions of fibronectin type III domain-containing 5 (FNDC5)/irisin were affected by burn injury, we introduced third-degree burn on the right hind paw of each rat [12,17,38]
We found that burn injury resulted in a decrease in FNDC5/irisin+ cells in both dorsal and ventral neuronal NeuN+ cells (Figure 1A)

Summary

Introduction

Neuropathy following burn trauma is common and often undiagnosed [1,2,3]. According to the WHO report, nearly 11 million severe burn injuries occur annually worldwide [4]. Patients with burn-related neuropathy often experience pain, paresthesia, or muscle weakness [2,7]. These long-term sequelae negatively affect quality of life and can be challenging to manage, which largely impact economic and social consequences on the patient, family, and society [8]. Our previous investigation indicated that neuroinflammation, autophagy, and neuronal apoptosis in the dorsal horn following burn contributed to burn-induced neuropathic pain [12]. Our previous study on a burn rat model indicated increased apoptosis in the spinal cord ventral horn postburn, resulting in denervation muscle atrophy [17]. An effective agent against burn-related neuropathic complications is required

Methods

Results

Conclusion