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Selective HDAC6 inhibition protects against blood-brain barrier dysfunction after intracerebral hemorrhage.


ABSTRACT:

Backgrounds

Blood-brain barrier (BBB) disruption after intracerebral hemorrhage (ICH) significantly induces neurological impairment. Previous studies showed that HDAC6 knockdown or TubA can protect the TNF-induced endothelial dysfunction. However, the role of HDAC6 inhibition on ICH-induced BBB disruption remains unknown.

Methods

Hemin-induced human brain microvascular endothelial cells (HBMECs) and collagenase-induced rats were employed to investigated the underlying impact of the HDAC6 inhibition in BBB lesion and neuronal dysfunction after ICH.

Results

We found a significant decrease in acetylated α-tubulin during early phase of ICH. Both 25 or 40 mg/kg of TubA could relieve neurological deficits, perihematomal cell apoptosis, and ipsilateral brain edema in ICH animal model. TubA or specific siRNA of HDAC6 inhibited apoptosis and reduced the endothelial permeability of HBMECs. HDAC6 inhibition rescued the degradation of TJ proteins and repaired TJs collapses after ICH induction. Finally, the results suggested that the protective effects on BBB after ICH induction were exerted via upregulating the acetylated α-tubulin and reducing stress fiber formation.

Conclusions

Inhibition of HDAC6 expression showed beneficial effects against BBB disruption after experimental ICH, which suggested that HDAC6 could be a novel and promising target for ICH treatment.

SUBMITTER: Peng C 

PROVIDER: S-EPMC10915991 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Selective HDAC6 inhibition protects against blood-brain barrier dysfunction after intracerebral hemorrhage.

Peng Cuiying C   Wang Yilin Y   Hu Zhiping Z   Chen Chunli C  

CNS neuroscience & therapeutics 20230904 3


<h4>Backgrounds</h4>Blood-brain barrier (BBB) disruption after intracerebral hemorrhage (ICH) significantly induces neurological impairment. Previous studies showed that HDAC6 knockdown or TubA can protect the TNF-induced endothelial dysfunction. However, the role of HDAC6 inhibition on ICH-induced BBB disruption remains unknown.<h4>Methods</h4>Hemin-induced human brain microvascular endothelial cells (HBMECs) and collagenase-induced rats were employed to investigated the underlying impact of th  ...[more]

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