Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (5): 1092-1097.doi: 10.4103/1673-5374.382861

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Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury

Qian Zhang1, #, Yao Jing2, #, Qiuyuan Gong2, #, Lin Cai2, Ren Wang2, Dianxu Yang2, Liping Wang3, 4, Meijie Qu4, 5, Hao Chen2, Yaohui Tang4, Hengli Tian1, *, Jun Ding1, *, Zhiming Xu2, *#br#   

  1. 1Department of Gerontology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of Neurosurgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; 3Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; 4School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China; 5Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
  • Online:2024-05-15 Published:2023-10-31
  • Contact: Hengli Tian, PhD, MD, tianhlsh@126.com; Jun Ding, PhD, MD, djdjdoc@126.com; Zhiming Xu, PhD, MD, zhiming0369@163.com.
  • Supported by:
    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).

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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.

Key words: angiogenesis, controlled cortical impact, endorepellin, neurological function, traumatic brain injury