USP18 overexpression protects against spinal cord ischemia/reperfusion injury via regulating autophagy

• Published in: Neuroscience letters 2023-07, Vol.810, p.137359-137359, Article 137359
• Main Authors: Yuan, Libang, Xu, Jin, Qin, Fuen, Yi, Xiaobo, Zhong, Zuling, Gu, Xiaoping, Gong, Gu
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Autophagy; Rats; Rats model; Rats, Sprague-Dawley; Reperfusion Injury - metabolism; Spinal Cord - metabolism; Spinal Cord Ischemia - metabolism; Spinal cord ischemia/reperfusion injury; USP18
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2023.137359

•USP18 overexpression protects against spinal cord ischemia/reperfusion (SCII) injury.•USP18 overexpression can alleviate neurological function and histological changes of the spinal cord after SCII. Spinal cord ischemia–reperfusion injury (SCII) is usually caused by spinal surgery, often leading to severe neurological deficits. The ubiquitin-specific protease 18 (USP18) plays a significant role in neurological diseases. The present study was designed to assess the effects and mechanisms of USP18 on SCII. By inducing transient aortic occlusion and subsequent reperfusion, a rat model of SCII was successfully established. The Basso-Beattie-Bresnahan scores, the inclined plane test, and hematoxylin and eosin (HE) were used to measure locomotor activity and histological changes in the injured spinal cords. Moreover, the SCII cell model was established using PC12 cells under oxygen-glucose deprivation and reoxygenation (OGD/R). Proinflammatory factors (TNF-α, IL-6, and INF-α) were examined using an ELISA kit. Cell apoptosis was assessed by Annexin V-FITC/PI double-staining and TUNEL assays. Western blot was used to detect the expression levels of proteins related to apoptosis and autophagy. USP18 expression was decreasedin vivo and in vitro SCII models. The upregulation of USP18 ameliorated hind limbs' motor function, inhibiting inflammation and apoptosis after SCII in rats. USP18 overexpression in vitro may protect PC12 cells from OGD/R-induced damage by modulating inflammatory responses and apoptosis. Moreover, Overexpression of USP18 enhanced autophagy to inhibit cell apoptosis induced by SCII in vivo and in vitro. In summary, USP18 overexpression protects against SCII via regulating autophagy.