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The Blood-brain Barrier00:49

The Blood-brain Barrier

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Blood-brain barrier dysfunction predicts cognitive trajectory after ischemic stroke.

Lei Xue, Olivia A Jones, Lauren Drag

    Biorxiv : the Preprint Server for Biology
    |March 23, 2026
    PubMed
    Summary

    Chronic stroke survivors show blood-brain barrier dysfunction, linked to cognitive decline. This dysfunction may be a key mechanism driving dementia after stroke, offering new biomarker and treatment targets.

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    Area of Science:

    • Neuroscience
    • Vascular Biology
    • Biomarkers

    Background:

    • Ischemic stroke significantly increases dementia risk, but the underlying mechanisms for late-stage cognitive decline remain unclear.
    • While early cognition is affected by stroke severity, late dementia risk is not associated with infarct characteristics or stroke prevention.
    • Existing research lacks understanding of the chronic mechanisms linking stroke to dementia.

    Purpose of the Study:

    • To investigate the role of chronic blood-brain barrier (BBB) dysfunction in cognitive decline following ischemic stroke.
    • To identify proteomic, imaging, and structural biomarkers associated with post-stroke dementia.
    • To explore potential therapeutic targets for preventing or treating cognitive impairment after stroke.

    Main Methods:

    • Plasma proteomic analysis was performed on stroke survivors and healthy controls to identify stroke-specific signatures.
    • Longitudinal cognitive assessments (processing speed/executive function) were conducted over two years.
    • Dynamic contrast-enhanced MRI was used to quantify BBB leakage in a cohort of stroke patients.
    • Autopsy brain tissue analysis compared vascular mural cell coverage in individuals with and without post-stroke dementia.

    Main Results:

    • A distinct plasma proteomic signature associated with chronic stroke and BBB dysfunction was identified, including decreased platelet-derived growth factor B.
    • This stroke-specific proteome was more pronounced in survivors experiencing cognitive decline in processing speed and executive function.
    • Stroke survivors exhibited significantly higher whole-brain BBB leakage (1.7-fold) compared to controls.
    • Individuals who died with dementia post-stroke showed a marked reduction in vascular mural cell coverage compared to those without dementia.

    Conclusions:

    • Chronic blood-brain barrier dysfunction is implicated as a key mechanism in late cognitive decline after ischemic stroke.
    • Proteomic and imaging findings suggest potential biomarkers for identifying individuals at risk of post-stroke dementia.
    • The study highlights vascular mural cell integrity and BBB function as critical factors and potential therapeutic targets for intervention.