Third-Degree Hindpaw Burn Injury Induced Apoptosis of Lumbar Spinal Cord Ventral Horn Motor Neurons and Sciatic Nerve and Muscle Atrophy in Rats

Abstract

Background. Severe burns result in hypercatabolic state and concomitant muscle atrophy that persists for several months, thereby limiting patient recovery. However, the effects of burns on the corresponding spinal dermatome remain unknown. This study aimed to investigate whether burns induce apoptosis of spinal cord ventral horn motor neurons (VHMNs) and consequently cause skeletal muscle wasting. Methods. Third-degree hindpaw burn injury with 1% total body surface area (TBSA) rats were euthanized 4 and 8 weeks after burn injury. The apoptosis profiles in the ventral horns of the lumbar spinal cords, sciatic nerves, and gastrocnemius muscles were examined. The Schwann cells in the sciatic nerve were marked with S100. The gastrocnemius muscles were harvested to measure the denervation atrophy. Result. The VHMNs apoptosis in the spinal cord was observed after inducing third-degree burns in the hindpaw. The S100 and TUNEL double-positive cells in the sciatic nerve increased significantly after the burn injury. Gastrocnemius muscle apoptosis and denervation atrophy area increased significantly after the burn injury. Conclusion. Local hindpaw burn induces apoptosis in VHMNs and Schwann cells in sciatic nerve, which causes corresponding gastrocnemius muscle denervation atrophy. Our results provided an animal model to evaluate burn-induced muscle wasting, and elucidate the underlying mechanisms.

Irisin Gene Delivery Ameliorates Burn-Induced Sensory and Motor Neuropathy

“…To identify whether spinal expressions of FNDC5/irisin were affected by burn injury, we introduced third-degree burn on the right hind paw of each rat [ 12 , 17 , 38 ]. The ipsilateral spinal cord of L4–L6 segments corresponding to innervation on the hind limb [ 39 ] and cerebrospinal fluid (CSF) were obtained at 4 weeks postburn.…”

“…An experimental full-thickness burn model indicated a reduction of conduction velocities postburn [ 16 ]. Our previous study on a burn rat model also indicated increased apoptosis in the spinal cord ventral horn postburn, resulting in denervation muscle atrophy [ 17 ]. Ma et al further indicated that microglial activation in the ventral horn resulted in neuronal apoptosis [ 18 ].…”

“…We previously reported that third-degree burn injury caused neuronal apoptosis in both ventral and dorsal horns, resulting in denervation muscle atrophy and neuropathic pain up to 4–8 weeks, respectively [ 12 , 17 , 38 ]. To elucidate the potential role of irisin in neuroprotection, we administered intrathecal irisin gene delivery in a third-degree burn rat model.…”

Erythropoietin Alleviates Burn-induced Muscle Wasting

“…The procedures were approved and conduced in accordance with the guidance of the Institutional Animal Care and Use Committee at Kaohsiung Medical University (IACUC Approval Number: 106047). On day 0 (D0), all animals received either a third-degree burn or sham burn injury and wound care following a previous thermal model [68]. The rats were randomly allocated into four groups of six rats each: (1) a sham-control group (sham burn group) which received a sham burn and no drug treatment;…”

“…The right hind paw of each rat topped with 100-g weight (to maintain a standardized surface contact) was placed, plantar side down, on a temperaturecontrolled metal surface for 10 seconds [68]. The metal surface was set at 25 ± 0.5°C for the sham burn group.…”