Evidence mapPaperPMID 41165828Full record

ArticleCellular and molecular life sciences : CMLS2025

The role of ROCK1/MLC/NMMHC IIA-actin signaling in ischemic stroke-induced blood-brain barrier disruption: implications for therapeutic intervention.

Liangying Bao, Yuanhao Xu, Yuchuan Ren, Yujie Dai, Junhe Yu, Milin Zhang, Shuaishuai Gong, Junping Kou

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Liangying Bao *State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
Yuanhao Xu *State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
Yuchuan RenState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
Yujie DaiState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
Junhe YuState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
Milin ZhangState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
Shuaishuai GongState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. 1520210030@cpu.edu.cn.
Junping KouState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. junpingkou@cpu.edu.cn.ORCID http://orcid.org/0000-0001-8377-915X

Funding

National Science Foundation No.8207142418
6 · The paper itself

Abstract

backgroundDisruption of the blood-brain barrier (BBB) is a key event in the onset of ischemic stroke (IS), primarily driven by endothelial cytoskeletal rearrangement. The interaction between non-muscle myosin heavy chain IIA (NMMHC IIA) and actin, along with the ROCK/MLC pathway, is central to this cytoskeletal reorganization. While our previous studies have shown that the Caspase-3/ROCK1/MLC/NMMHC IIA-actin positive feedback loop mediates H

methodsIn vivo, we used endothelial-specific NMMHC IIA conditional knockdown mice, NMMHC IIA-inducible endothelial conditional knock-in mice and C57BL/6J to establish a middle cerebral artery occlusion/reperfusion model. In vitro, we employed brain microvascular endothelial cells in an oxygen-glucose deprivation/reoxygenation model. The effects of the NMMHC IIA inhibitor blebbistatin, the ROCK1 inhibitor Y-27632, and the actin depolymerizer cytochalasin D were assessed for their impact on I/R-induced activation of the ROCK/MLC/NMMHC IIA-actin pathway, tight junction proteins (TJs) degradation, and brain damage.

resultsInhibition of NMMHC IIA expression and stress fiber depolymerization significantly reduced NMMHC IIA-actin interactions, suppressed the ROCK/MLC pathway, decreased TJs degradation, and alleviated cerebral I/R injury. Conversely, overexpression of NMMHC IIA further exacerbated cerebral I/R injury and BBB disruption and amplified activation of the ROCK1/MLC pathway. Y-27632 inhibited the ROCK/MLC/NMMHC IIA-actin pathway, mitigating I/R-induced BBB disruption.

conclusionsThis study reveals that the ROCK1/MLC/NMMHC IIA-actin pathway is implicated in I/R-induced BBB disruption and operates as a positive feedback loop. These findings offer a promising therapeutic strategy for the treatment of IS and BBB damage.

Indexed as

ActinsBlood-Brain BarrierIschemic StrokeMyosin Heavy ChainsMyosin Light ChainsNonmuscle Myosin Type IIArho-Associated KinasesSignal TransductionAmidesAnimalsDisease Models, AnimalEndothelial CellsMaleMiceMice, Inbred C57BLReperfusion InjuryActinsAmidesMyosin Heavy ChainsMyosin Light ChainsNonmuscle Myosin Type IIArho-Associated KinasesRock1 protein, mouseBlood-brain barrier disruptionIschemic strokeROCK1/MLC/NMMHC IIA-actin loopTight junction

Identifiers

PMID41165828
PMCPMC12575896

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.