2. Academic Validation
  3. Acetylation of α-tubulin restores endothelial cell injury and blood-brain barrier disruption after intracerebral hemorrhage in mice

Acetylation of α-tubulin restores endothelial cell injury and blood-brain barrier disruption after intracerebral hemorrhage in mice

  • Exp Mol Med. 2025 May;57(5):1064-1077. doi: 10.1038/s12276-025-01454-9.
Xuejiao Lei # 1,  Eryi Sun # 2,  Xufang Ru 1,  Yulian Quan 1,  Xuezhu Chen 3,  Qian Zhang 4,  Yougling Lu 4,  Qianying Huang 4,  Yujie Chen 1,  Wenyan Li 1,  Hua Feng 5 6,  Yang Yang 7 8 9,  Rong Hu 10
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • 2 Department of Neurosurgery, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.
  • 3 Department of Pathology, Public Health Medical Center, Chongqing, China.
  • 4 Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • 5 Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. fenghua8888@vip.163.com.
  • 6 State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China. fenghua8888@vip.163.com.
  • 7 Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. yangyang200905@tmmu.edu.cn.
  • 8 State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China. yangyang200905@tmmu.edu.cn.
  • 9 Department of Neurosurgery, The 904th Hospital of PLA, Anhui Medical University, Wuxi, China. yangyang200905@tmmu.edu.cn.
  • 10 Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. huchrong@tmmu.edu.cn.
  • # Contributed equally.
PMID: 40335634 DOI: 10.1038/s12276-025-01454-9
Abstract

Damage to endothelial cells (ECs) is a key factor in blood-brain barrier (BBB) disruption after intracerebral hemorrhage (ICH). While microtubules are essential for EC structure, their role in BBB injury remains unclear. Here we investigated the role of acetylated α-tubulin (α-Ac-Tub) in BBB integration after ICH. Using an autologous blood injection model in the striatum, we showed that the expression of α-Ac-Tub and MEC17, an α-tubulin acetyltransferase, significantly decreased along the vessels around the hematoma after ICH. Conditional MEC17 knockout in ECs further reduced α-Ac-Tub levels and exacerbated BBB leakage, brain edema, hematoma expansion, inflammation and motor dysfunction. Conversely, selective α-Ac-Tub upregulation in ECs via intravenous delivery of AAV-BI30-MEC17-GFP alleviated BBB dysfunction and improved motor recovery. Similarly, the HDAC6 Inhibitor tubastatin A enhanced α-Ac-Tub levels, mitigating BBB damage and neurological deficits. Mechanistically, α-Ac-Tub deficiency in ECs reduced tight junction proteins (ZO-1 and Claudin5) and increased F-actin stress fibers through RhoA activation. Together, our findings highlighted α-Ac-Tub as a therapeutic target for restoring BBB function and reducing brain injury after ICH.

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