CKLF1 Serves as a Pivotal Mediator of Blood-Brain Barrier Disruption and Neuroinflammation via PI3K/AKT/mTOR Signaling in Ischemic Stroke.
G, H., J, W., J, W., T, L., & Z, S. (2026). CKLF1 Serves as a Pivotal Mediator of Blood-Brain Barrier Disruption and Neuroinflammation via PI3K/AKT/mTOR Signaling in Ischemic Stroke.. Molecular neurobiology. https://doi.org/10.1007/s12035-026-06119-w
G H, J W, J W, T L, Z S. CKLF1 Serves as a Pivotal Mediator of Blood-Brain Barrier Disruption and Neuroinflammation via PI3K/AKT/mTOR Signaling in Ischemic Stroke.. Molecular neurobiology. 2026; doi: 10.1007/s12035-026-06119-w
G H, J W, J W, et al. CKLF1 Serves as a Pivotal Mediator of Blood-Brain Barrier Disruption and Neuroinflammation via PI3K/AKT/mTOR Signaling in Ischemic Stroke.[J]. Molecular neurobiology. 2026. DOI: 10.1007/s12035-026-06119-w.
@article{g2026,
author = {Hou G and Wang J and Wang J and Li T and Song Z},
title = {CKLF1 Serves as a Pivotal Mediator of Blood-Brain Barrier Disruption and Neuroinflammation via PI3K/AKT/mTOR Signaling in Ischemic Stroke.},
journal = {Molecular neurobiology},
year = {2026},
doi = {10.1007/s12035-026-06119-w},
note = {PMID: 42608489},
}
TY - JOUR AU - Hou G AU - Wang J AU - Wang J AU - Li T AU - Song Z TI - CKLF1 Serves as a Pivotal Mediator of Blood-Brain Barrier Disruption and Neuroinflammation via PI3K/AKT/mTOR Signaling in Ischemic Stroke. T2 - Molecular neurobiology PY - 2026 DO - 10.1007/s12035-026-06119-w AN - PMID:42608489 ER -
Ischemic stroke (IS) is accompanied by blood-brain barrier (BBB) disruption and neuroinflammatory activation, but the upstream regulatory mechanisms remain incompletely defined. Here, integrated single-cell RNA sequencing, regulatory network analysis, and machine-learning screening identified Chemokine-like factor 1 (CKLF1) as a candidate endothelial regulator associated with IS. Functional validation showed that CKLF1 upregulation impaired endothelial barrier integrity, reduced tight-junction protein expression, enhanced apoptosis-associated activity, and activated PI3K/AKT/mTOR signaling under ischemic stress. CKLF1 also promoted chemokine amplification, microglial pro-inflammatory activation, and peripheral neutrophil recruitment. In a tMCAO/R mouse model, pharmacological inhibition of CKLF1 improved neurological outcomes, reduced infarct volume, preserved BBB integrity, and attenuated inflammatory activation, particularly when combined with CCL2 blockade. Conversely, CKLF1⁺ extracellular vesicle (EV)-related treatment aggravated BBB permeability and neuroinflammation. These findings support CKLF1 as a mediator of post-stroke endothelial injury and immune-inflammatory crosstalk and suggest that CKLF1-targeted intervention may represent a potential strategy for limiting BBB disruption after IS.