1. Academic Validation
  2. GM130 protects against blood-brain barrier disruption and brain injury after intracerebral hemorrhage by regulating autophagy formation

GM130 protects against blood-brain barrier disruption and brain injury after intracerebral hemorrhage by regulating autophagy formation

  • Exp Gerontol. 2022 Jun 15;163:111772. doi: 10.1016/j.exger.2022.111772.
Shuwen Deng 1 Qing Hu 1 Xiqian Chen 1 Qiang Lei 2 Wei Lu 3
Affiliations

Affiliations

  • 1 Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
  • 2 Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Electronic address: leiqiang18@csu.edu.cn.
  • 3 Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Electronic address: luwei0338@csu.edu.cn.
Abstract

Blood-brain barrier (BBB) disruption following intracerebral hemorrhage (ICH) significantly contributes to neurological deficits. Tight junction (TJ) protein loss in brain endothelial cells leads to BBB disruption. We previously revealed the importance of the Golgi apparatus (GA) in maintaining TJ integrity in mouse brain endothelial (bEnd.3) cells, but the specific mechanisms remain unknown. Herein, we investigated the potential role of the GA in BBB damage and neurological dysfunction after ICH using bEnd.3 cells and hemin to mimic hemorrhage in vitro. We used a rat hemorrhage stroke model to evaluate the role of the GA in BBB disruption during ICH. GM130 levels decreased with ICH length in vivo and in vitro. TJ protein destruction further increased following GM130 silencing. GM130 overexpression alleviated TJ protein impairment and improved BBB integrity. bEnd.3 cells treated with an Autophagy Inhibitor showed reduced TJ protein damage following GM130 silencing. The intracerebroventricular injection of an Autophagy Inhibitor rescued GM130 silencing-induced BBB leakage. Thus, TJ proteins were destroyed by excessive autophagic pathway activation following ICH, whereas GM130 protected against TJ damage by maintaining proper Autophagy. We suggest that GM130-regulated selective Autophagy modulates BBB integrity and GM130 upregulation suppresses the autophagy-lysosome pathway, which might maintain BBB function. Therefore, GA protection is beneficial for ICH, and GM130 is a potential therapeutic target for its treatment.

Keywords

Blood brain barrier; Golgi apparatus; Intracerebral hemorrhage; Tight junction proteins.

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