muramidase and Infarction--Middle-Cerebral-Artery

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 TAK1. Infarcts were significantly smaller in TAK1. Our results showed that deletion of myeloid TAK1 resulted in smaller infarcts and improved functional outcomes at the peak of inflammation (day 3) and a reduction in brain-infiltrating immune cells that were primarily monocytes. Myeloid TAK1 deletion was also protective at 7 days post MCAo, reflecting a detrimental role of myeloid TAK1 in the progression of ischemic injury.

Topics: Animals; Antigens, CD; Cerebrovascular Circulation; Disease Models, Animal; Flow Cytometry; Infarction, Middle Cerebral Artery; Male; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Monocytes; Muramidase; Myeloid Cells; Neutrophil Infiltration; Neutrophils; Recovery of Function