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Abstract
Interleukin-1 (IL-1) signaling is a major driver of post-ischemic neuroinflammation, yet the cell- and isoform-specific roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1β, remain incompletely defined in the context of stroke. Microglia rapidly express IL-1α after cerebral ischemia, whereas IL-1β expression is delayed and restricted to a small subset of microglia and infiltrating immune cells. Here, we investigated for the first time the specific contribution of microglial-derived IL-1β to acute injury and post-stroke neurorepair after transient middle cerebral artery occlusion in male and female mice, through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Deletion of microglial IL-1β improved acute neurological outcome, reduced neutrophil accumulation in the ischemic brain and dampened systemic inflammatory cytokines. These effects were most evident during the acute phase and in female in mice. In contrast, long-term functional recovery was largely unaffected. However, microglial IL-1β deletion differentially regulated post-stroke neurogenesis, enhancing subventricular zone neurogenic responses and ectopic neuroblast migration while limiting hippocampal neurogenesis. Together, these findings identify microglial IL-1β as a key amplifier of early inflammatory injury after stroke, exerting region-specific effects on neurogenic niches, and highlight distinct, non-redundant roles for microglial IL-1 isoforms in ischemic brain injury and repair.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Authors details (email address): Alba Grayston, alba.grayston-morales{at}manchester.ac.uk, Margarida Baptista, margarida.baptista{at}postgrad.manchester.ac.uk, Kelly Wemyss, kelly.wemyss{at}manchester.ac.uk, Ruby Taylor, rubytayylor0{at}gmail.com, Grace Cullen, gracecullen{at}live.com, Syeda S Jafree, sarahjafree{at}gmail.com Nadim Luka, n.luka{at}qmul.ac.uk, Joshua R Cox, joshua.cox{at}manchester.ac.uk, Joanne E Konkel, joanne.konkel{at}manchester.ac.uk, David Brough, david.brough{at}manchester.ac.uk, Stuart M Allan, stuart.allan{at}manchester.ac.uk
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