IL-4/STAT6 signaling facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

• DOI: 10.1073/pnas.2018497117
• Publication Date: 2020-12-08T19:00:50Z
• Authors: Jing Xu; Zhouqing Chen; Fang Yu; Huan Liu; Cheng Ma; Di Xie; Xiaoming Hu; Rehana K. Leak; Sherry H. Y. Chou; R. Anne Stetler; Yejie Shi; Jun Chen; Michael V. L. Ben...; Gang Chen
• Keywords: Stroke

Intracerebral hemorrhage (ICH) is a devastating form of stroke affecting millions people worldwide. Parenchymal hematoma triggers series reactions leading to primary and secondary brain injuries permanent neurological deficits. Microglia macrophages carry out clearance, thereby facilitating functional recovery after ICH. Here, we elucidate pivotal role for the interleukin (IL)-4)/signal transducer activator transcription 6 (STAT6) axis in promoting long-term both blood- collagenase-injection mouse models ICH, through modulation microglia/macrophage functions. In ICH models, STAT6 was activated microglia/macrophages (i.e., enhanced expression phospho-STAT6 Iba1+ cells). Intranasal delivery IL-4 nanoparticles hastened activation facilitated resolution. treatment improved young aged male female mice. contrast, knockout (KO) mice exhibited worse outcomes than WT were less responsive treatment. The construction bone marrow chimera demonstrated that KO either CNS or periphery exacerbated outcomes. impaired capacity phagocytes engulf red blood cells cultures. Transcriptional analyses identified lower level IL-1 receptor-like 1 (ST2) ST2 diminished beneficial effects Collectively, these data confirm importance IL-4/STAT6/ST2 signaling resolution warrants further investigation as clinically feasible therapy