Perihematomal edema
(PHE) occurs within hours after intracerebral hemorrhage (ICH), leading
to secondary injury manifested by impaired blood–brain barrier (BBB)
integrity and destruction of adjacent tissue. To dissect the mechanisms
underlying PHE formation, we profiled human and mouse perihematomal
tissues and identified natural killer (NK) cells as the predominant
immune cell subset that outnumbers other infiltrating immune cell types
during early stages of ICH. Unbiased clustering of single-cell
transcriptional profiles revealed two major NK cell subsets that
respectively possess high cytotoxicity or robust chemokine production
features in the brain after ICH, distinguishing them from NK cells of
the periphery. NK cells exacerbate BBB disruption and brain edema after
ICH via cytotoxicity toward cerebral endothelial cells and recruitment
of neutrophils that augment focal inflammation. Thus, brain-bound NK
cells acquire new features that contribute to PHE formation and
neurological deterioration following ICH.
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