Myeloid-specific TAK1 deletion results in reduced brain monocyte infiltration and improved outcomes after stroke

Journal of Neuroinflammation
Anjali ChauhanLouise D McCullough

Abstract

Activation of transforming growth factor-β-activated kinase 1 (TAK1) occurs after stroke and leads to an exacerbation of brain injury. TAK1 is involved in innate and adaptive immune responses, but it has divergent inflammatory effects that are dependent on the cell type in which it is activated. There is a robust infiltration of myeloid cells after stroke; however, the contribution of myeloid TAK1 to cerebral ischemia is currently unknown. We hypothesized that myeloid-specific deletion of TAK1 would protect against ischemic brain injury. Myeloid TAK1ΔM and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAo). Brain-infiltrating and splenic immune cells were evaluated at 3 days after stroke. Assessment of infarct size and behavioral deficits were performed on days 3 and 7 post-stroke. Infarcts were significantly smaller in TAK1ΔM mice (p < 0.01), and behavioral deficits were less severe despite equivalent reduction in cerebral blood flow. Flow cytometry demonstrated an increase in the frequency of splenic monocytes and neutrophils (p < 0.05) and a decrease in splenic CD3+ T (p < 0.01) and CD19+ B (p = 0.06) cells in TAK1ΔM mice compared to WT at baseline. Three days after stroke, a significant increase i...Continue Reading

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Citations

May 10, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Thomas ZeyenPardes Habib
Jan 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Abdullah Al MamunFudong Liu
May 21, 2020·Journal of Neuroinflammation·Maria Pilar BlascoBhanu Priya Ganesh
Jan 5, 2021·Autism Research : Official Journal of the International Society for Autism Research·Xinyan XieRanran Song
Nov 17, 2020·Frontiers in Neurology·Joohyun ParkJong Eun Lee

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ubiquitination

Software Mentioned

Sigmascan Pro
Sigma Scan Pro
GraphPad Prism
FlowJo

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