Loss of Endothelial Laminin α5 Exacerbates Hemorrhagic Brain Injury


Endothelial cells make laminin-411 and laminin-511. Although laminin-411 is well studied, the role of laminin-511 remains largely unknown due to the embryonic lethality of lama5−/− mutants. In this study, we generated endothelium-specific lama5 conditional knockout (α5-TKO) mice and investigated the biological functions of endothelial lama5 in blood-brain barrier (BBB) maintenance under homeostatic conditions and the pathogenesis of intracerebral hemorrhage (ICH). First, the BBB integrity of α5-TKO mice was measured under homeostatic conditions. Next, ICH was induced in α5-TKO mice and their littermate controls using the collagenase model. Various parameters, including injury volume, neuronal death, neurological score, brain edema, BBB integrity, inflammatory cell infiltration, and gliosis, were examined at various time points after injury. Under homeostatic conditions, comparable levels of IgG or exogenous tracers were detected in α5-TKO and control mice. Additionally, no differences in tight junction expression, pericyte coverage, and astrocyte polarity were found in these mice. After ICH, α5-TKO mice displayed enlarged injury volume, increased neuronal death, elevated BBB permeability, exacerbated infiltration of inflammatory cells (leukocytes, neutrophils, and mononuclear cells), aggravated gliosis, unchanged brain edema, and worse neurological function, compared to the controls. These findings suggest that endothelial lama5 is dispensable for BBB maintenance under homeostatic conditions but plays a beneficial role in ICH.

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We thank the Yao Lab members for discussions and suggestions.


This study was supported, in part, by the American Heart Association grant 16SDG29320001 (to YY) and NIH R01DK078314 (to JHM).

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Correspondence to Yao Yao.

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The authors declare that they have no conflict of interest.

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All applicable international. National, and/or institutional guidelines for the care and use of animals were followed. This study was approved by the Institutional Animal Care and Use Committee at the University of Georgia. This study does not contain any studies with human participants performed by any of the authors.

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Gautam, J., Miner, J.H. & Yao, Y. Loss of Endothelial Laminin α5 Exacerbates Hemorrhagic Brain Injury. Transl. Stroke Res. 10, 705–718 (2019). https://doi.org/10.1007/s12975-019-0688-5

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  • Intracerebral hemorrhage
  • Blood-brain barrier
  • Endothelial cells
  • Laminin