Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury

Qian Zhang; Yao Jing; Qiuyuan Gong; Lin Cai; Ren Wang; Dianxu Yang; Liping Wang; Meijie Qu; Hao Chen; Yaohui Tang; Hengli Tian; Jun Ding; Zhiming Xu

doi:10.4103/1673-5374.382861

Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury

Neural Regen Res. 2024 May;19(5):1092-1097. doi: 10.4103/1673-5374.382861.

Authors

Qian Zhang¹, Yao Jing², Qiuyuan Gong², Lin Cai², Ren Wang², Dianxu Yang², Liping Wang³, Meijie Qu⁴, Hao Chen², Yaohui Tang⁵, Hengli Tian¹, Jun Ding¹, Zhiming Xu²

Affiliations

¹ Department of Gerontology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Neurosurgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Neurology, Renji Hospital, School of Medicine; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
⁴ School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai; Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
⁵ School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Endorepellin plays a key role in the regulation of angiogenesis, but its effects on angiogenesis after traumatic brain injury are unclear. This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice. Mice were randomly divided into four groups: sham, controlled cortical impact only, adeno-associated virus (AAV)-green fluorescent protein, and AAV-shEndorepellin-green fluorescent protein groups. In the controlled cortical impact model, the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31⁺/Ki-67⁺ proliferating endothelial cells and the functional microvessel density in mouse brain. These changes resulted in improved neurological function compared with controlled cortical impact mice. Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein. Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization, which may further improve neurobehavioral outcomes. Furthermore, an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control. Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor- and angiopoietin-1-related signaling pathways.

Keywords: angiogenesis; controlled cortical impact; endorepellin; neurological function; traumatic brain injury.

Grants and funding

Funding: This study was supported by the National Natural Science Foundation of China, Nos. 81801236 (to ZX), 81974189 (to HT) and a grant from Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. ynlc201719 (to QZ).