Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury.

Akihiko Uchiyama,Kazuya Yamada,Sei-ichiro Motegi,Yoko Yokoyama,Buddhini Perera,Sachiko Ogino,Osamu Ishikawa,Yuko Takeuchi

doi:10.1038/srep09072

Akihiko Uchiyama, Kazuya Yamada + Show 6 more

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https://doi.org/10.1038/srep09072

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Journal: Scientific Reports	Publication Date: Mar 13, 2015
Citations: 46	License type: CC BY 4.0

Affiliation: Gunma University

Abstract

Botulinum toxin A (BTX-A) blocks the release of acetylcholine vesicles into the synaptic space, and has been clinically used for aesthetic indications, neuromuscular disorders and hyperhidrosis. Several studies have demonstrated that BTX-A enhanced the blood flow and improved ischemia in animal models. Our objective was to assess the effects of BTX-A on cutaneous ischemia-reperfusion (I/R) injuries, mimicking decubitus ulcers. The administration of BTX-A in I/R areas significantly inhibited the formation of decubitus-like ulcer in cutaneous I/R injury mouse model. The number of CD31+ vessels and αSMA+ pericytes or myofibroblasts in wounds were significantly increased in the I/R mice treated with BTX-A. The hypoxic area and the number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R sites were reduced by BTX-A administration. In an in vitro assay, BTX-A significantly prevented the oxidant-induced intracellular accumulation of reactive oxygen species (ROS) in vascular endothelial cells. Furthermore, the administration of BTX-A completely suppressed the ulcer formation in an intermittent short-time cutaneous I/R injury model. These results suggest that BTX-A might have protective effects against ulcer formation after cutaneous I/R injury by enhancing angiogenesis and inhibiting hypoxia-induced cellular damage. Exogenous application of BTX-A might have therapeutic potential for cutaneous I/R injuries.

Highlights

Akihiko Uchiyama*, Kazuya Yamada, Buddhini Perera, Sachiko Ogino, Yoko Yokoyama, Yuko Takeuchi, Osamu Ishikawa & Sei-ichiro Motegi*
From four to nine days after reperfusion, the wound areas in 1.0 U Botulinum toxin A (BTX-A)-treated mice were significantly smaller than those in control mice. These results suggest that Botulinum toxin (BTX)-A might have the potential to prevent the development of cutaneous pressure ulcers after I/R injury
We first assessed the vascular damage induced by I/R injury, and found that the numbers of CD311 endothelial cells and aSMA1 pericytes or myofibroblasts in I/R areas in BTX-A-treated mice were significantly higher than those in control mice. These results suggest that BTX-A could protect against vascular damages by I/R injury

Summary

Introduction

Akihiko Uchiyama*, Kazuya Yamada, Buddhini Perera, Sachiko Ogino, Yoko Yokoyama, Yuko Takeuchi, Osamu Ishikawa & Sei-ichiro Motegi*. Our objective was to assess the effects of BTX-A on cutaneous ischemia-reperfusion (I/R) injuries, mimicking decubitus ulcers. The administration of BTX-A in I/R areas significantly inhibited the formation of decubitus-like ulcer in cutaneous I/R injury mouse model. The hypoxic area and the number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R sites were reduced by BTX-A administration. The administration of BTX-A completely suppressed the ulcer formation in an intermittent short-time cutaneous I/R injury model. These results suggest that BTX-A might have protective effects against ulcer formation after cutaneous I/R injury by enhancing angiogenesis and inhibiting hypoxia-induced cellular damage. There is a broad spectrum of other indications for migraine, achalasia, urinary bladder dysfunction and anal fissures[15,16,17,18,19]

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