Reduced neuropeptide signaling attenuates ischemia–reperfusion–induced pressure ulcer formation in SOD1-G93A mice
- 1Department of Dermatology, Gunma University Graduate School of Medicine
Abstract
Amyotrophic lateral sclerosis (ALS) has been suggested to be associated with a reduced incidence of pressure ulcers, although the underlying mechanisms remain unclear. Here, we investigated pressure ulcer formation using a cutaneous ischemia–reperfusion (I/R) injury model in SOD1-G93A mice, a model of familial ALS. Under steady-state conditions, oxidative stress was markedly elevated in the dorsal root ganglia (DRG) and spinal cord compared with skin, accompanied by reduced PGP9.5+ nerve fiber density in the skin. Following I/R injury, SOD1-G93A mice exhibited significantly attenuated ulcer formation during the early phase after reperfusion compared with wild-type mice. Quantitative PCR analysis demonstrated the reduced expression of oxidative stress-related genes, proinflammatory cytokines, and neuropeptides and their receptors in I/R skin site. Histological analyses revealed reduced infiltration of M1 macrophages, decreased 8-OHdG-positive oxidative DNA damage, and fewer apoptotic cells. Consistently, a denervation model showed reduced wound size after cutaneous I/R injury. Despite elevated oxidative stress in DRG and spinal cord, cutaneous oxidative and inflammatory responses were suppressed in SOD1-G93A mice. These findings suggest that impaired peripheral innervation attenuates neuropeptide-mediated inflammatory pathways, thereby reducing tissue injury following I/R and leading to decreased pressure ulcer formation in ALS.
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BibTeX
@article{uchiyama2026reduced,
title = {{Reduced neuropeptide signaling attenuates ischemia–reperfusion–induced pressure ulcer formation in SOD1-G93A mice}},
author = {Akihiko Uchiyama and Akiko Sekiguchi and Yuta Inoue and Shintaro Saito and Keiji Kosaka and Mayu Ohtaka and Takeshi Araki and Takayuki Shuto and Azusa Ida and Yoko Yokoyama and Sachiko Ogino and Ryoko Torii and Yuki Watanuki and Sei-ichiro Motegi},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-63449-4},
url = {https://doi.org/10.1038/s41598-026-63449-4},
note = {CC BY},
}
RIS
TY - JOUR
TI - Reduced neuropeptide signaling attenuates ischemia–reperfusion–induced pressure ulcer formation in SOD1-G93A mice
AU - Akihiko Uchiyama
AU - Akiko Sekiguchi
AU - Yuta Inoue
AU - Shintaro Saito
AU - Keiji Kosaka
AU - Mayu Ohtaka
AU - Takeshi Araki
AU - Takayuki Shuto
AU - Azusa Ida
AU - Yoko Yokoyama
AU - Sachiko Ogino
AU - Ryoko Torii
AU - Yuki Watanuki
AU - Sei-ichiro Motegi
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-63449-4
UR - https://doi.org/10.1038/s41598-026-63449-4
AB - Amyotrophic lateral sclerosis (ALS) has been suggested to be associated with a reduced incidence of pressure ulcers, although the underlying mechanisms remain unclear. Here, we investigated pressure ulcer formation using a cutaneous ischemia–reperfusion (I/R) injury model in SOD1-G93A mice, a model of familial ALS. Under steady-state conditions, oxidative stress was markedly elevated in the dorsal root ganglia (DRG) and spinal cord compared with skin, accompanied by reduced PGP9.5+ nerve fiber density in the skin. Following I/R injury, SOD1-G93A mice exhibited significantly attenuated ulcer formation during the early phase after reperfusion compared with wild-type mice. Quantitative PCR analysis demonstrated the reduced expression of oxidative stress-related genes, proinflammatory cytokines, and neuropeptides and their receptors in I/R skin site. Histological analyses revealed reduced infiltration of M1 macrophages, decreased 8-OHdG-positive oxidative DNA damage, and fewer apoptotic cells. Consistently, a denervation model showed reduced wound size after cutaneous I/R injury. Despite elevated oxidative stress in DRG and spinal cord, cutaneous oxidative and inflammatory responses were suppressed in SOD1-G93A mice. These findings suggest that impaired peripheral innervation attenuates neuropeptide-mediated inflammatory pathways, thereby reducing tissue injury following I/R and leading to decreased pressure ulcer formation in ALS.
SN - 2045-2322
ER -