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Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury

Qian Zhang1, Yao Jing2, Qiuyuan Gong2

  • 1Department of Gerontology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Neural Regeneration Research
|October 20, 2023
PubMed

Insights

Downregulating endorepellin after traumatic brain injury promotes angiogenesis and improves neurobehavioral outcomes in mice by activating key growth factor pathways.

Area of Science:

  • Neuroscience
  • Vascular Biology
  • Regenerative Medicine

Background:

  • Endorepellin regulates angiogenesis, but its role in traumatic brain injury (TBI) recovery is unknown.
  • Traumatic brain injury can lead to impaired angiogenesis and neurological deficits.

Purpose of the Study:

  • To investigate the effects of endorepellin on angiogenesis and neurobehavioral outcomes following TBI in a mouse model.
  • To explore the underlying molecular mechanisms of endorepellin's influence on TBI recovery.

Main Methods:

  • A controlled cortical impact model of TBI was used in mice.
  • Adeno-associated virus (AAV)-shEndorepellin was administered to downregulate endorepellin expression.
  • Angiogenesis markers (CD31+/Ki-67+ cells, microvessel density), neurobehavioral tests, Western blotting, and synchrotron radiation angiography were employed.
  • In vitro studies using human umbilical vein endothelial cells assessed tube formation.

Main Results:

  • Downregulation of endorepellin via AAV-shEndorepellin increased proliferating endothelial cells and microvessel density in the injured brain.
  • Endorepellin downregulation led to improved neurobehavioral outcomes compared to control TBI mice.
  • Vascular endothelial growth factor (VEGF) and angiopoietin-1 expression increased following endorepellin downregulation.
  • In vitro, endorepellin knockdown enhanced endothelial cell tube formation.

Conclusions:

  • Endorepellin downregulation promotes angiogenesis and cortical neovascularization after TBI.
  • This pro-angiogenic effect, mediated by VEGF and angiopoietin-1 pathways, contributes to improved neurological function and neurobehavioral recovery.
  • Targeting endorepellin represents a potential therapeutic strategy for TBI.
Keywords:
angiogenesiscontrolled cortical impactendorepellinneurological functiontraumatic brain injury

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