Work

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

Year: 2025

Type: article

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.

Source: Experimental & Molecular Medicine

DOI: 10.1038/s12276-025-01454-9