Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption.
Overview
- Division of Medical Sciences, University of Victoria,Victoria, BC Canada
- Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf,Hamburg, Germany
- Department of Psychiatry, University of British Columbia,Vancouver, BC Canada
Abstract
Focal stroke leads to complex changes in the cerebral microcirculation in surviving brain tissues that strongly influence functional recovery. The gene Serpine1 and its protein product Plasminogen Activator-Inhibitor-1 (PAI-1), are highly upregulated in endothelial cells after stroke, are known to inhibit clot breakdown and are an established biomarker of cardiovascular disease in humans. Therefore, we hypothesized that inhibiting this pathway specifically within brain endothelial cells could be beneficial for stroke recovery by promoting fibrinolysis and cerebral blood flow (CBF). Using longitudinal in vivo imaging, we first show in wild-type mice that focal ischaemic stroke leads to a transient reduction in peri-infarct CBF at 6 h (~41%), which is then followed by hyperperfusion at 3 days (~29%). Contrary to expectation, viral knockdown of Serpine1 in brain endothelial cells led to a persistent reduction in peri-infarct capillary width (~20–37%) and red blood cell velocity (~36–50%) over this time. Consistent with this effect on CBF, topical application of PAI-1 increased capillary diameter and flow. Of note, lowered peri-infarct CBF in Serpine1 knockdown mice appeared to play a protective role in stroke recovery since it attenuated deleterious blood-brain barrier disruption and pro-inflammatory gene expression. In agreement with this, Serpine1 knockdown mice displayed enhanced recovery of sensory evoked cortical responses, as well as improved cognitive and sensorimotor function relative to wild-type mice. These findings suggest that endothelial Serpine1/
Reproduced under the paper's license (CC BY), from the paper cited above.
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All data and code generated for the study are available from the corresponding author upon reasonable request. Transcriptomic datasets generated during and/
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Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 3 keywords, 13 MeSH terms, 77 references.
Cite
This paper
Narayana, K., Lambert, I. C., Burford, S., Gosselin, E., Körbelin, J., & Brown, C. E. (2026). Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption. Cell death & disease, 17(1), 800. https://
BibTeX
@article{narayana2026kno
author = {Narayana, Kamal and Lambert, Isabel C. and Burford, Sam and Gosselin, Emilie and Körbelin, Jakob and Brown, Craig E.},
title = {{Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption}},
journal = {Cell death \& disease},
year = {2026},
month = jun,
volume = {17},
number = {1},
pages = {800},
publisher = {Nature Publishing Group},
issn = {2041-4889},
doi = {10.1038/
url = {https://
pmid = {42373606},
pmcid = {PMC13575155}
}
RIS
TY - JOUR
AU - Narayana, Kamal
AU - Lambert, Isabel C.
AU - Burford, Sam
AU - Gosselin, Emilie
AU - Körbelin, Jakob
AU - Brown, Craig E.
TI - Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption
T2 - Cell death & disease
J2 - Cell Death Dis
PY - 2026
DA - 2026/
VL - 17
IS - 1
SP - 800
SN - 2041-4889
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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"family": "Narayana",
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"given": "Isabel C."
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"page": "800",
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"language": "en",
"issued": {
"date-parts": [
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