Keun Woo Park1,2, Hyunwoo Ju1, Il-Doo Kim1, John W Cave3, Yang Guo1, Wei Wang4, Zhuhao Wu4, Sunghee Cho1,2. 1. Burke Neurological Institute, White Plains, NY (K.W.P., H.J., I.-d.K., Y.G., S.C.). 2. Feil Brain Mind Research Institute, Weill Cornell Medicine, NY (K.W.P., S.C.). 3. InVitro Cell Research LLC, Englewood, NJ (J.W.C.). 4. Department of Cell, Developmental and Regenerative Biology and Department of Neuroscience, Icahn School of Medicine at Mount Sinai, NY (W.W., Z.W.).
Abstract
BACKGROUND: Mononuclear phagocytes, including monocyte-derived macrophages (MDMs) and microglia, contribute to infarct development as well as tissue repair in the postischemic brain. Here, we identify the origin and function of MDMs in the brain during poststroke repair processes. METHODS: Adult mice were subjected to transient middle cerebral artery occlusion. Longitudinal brain atrophy and secondary degeneration were evaluated during acute to recovery phases of stroke. Adoptive transfer of GFP+ splenocytes into asplenic mice was used to distinguish MDMs from resident microglia. Fluorescence beads were injected into stroked animals to examine phagocytic function. RESULTS: Progressive atrophy and neuronal degeneration in remote regions were observed in chronic stroke, which also was accompanied by MDM infiltration into the ipsilateral hemisphere. Compared with microglia, MDMs had significantly higher phagocytic activity. MDM trafficking and phagocytosis was spatiotemporally regulated with acute and prolonged infiltration into infarcted tissue, as well as delayed entry in remote areas such as the thalamus and substantia nigra. CONCLUSIONS: The stepwise and long-lasting involvement of MDMs at multiple poststroke stages shows that MDMs have a role in progressive stroke-induced injury and repair processes. These findings suggest that manipulating monocyte entry at different stroke stages may be an effective immune-based strategy to limit injury propagation in chronic stroke.
BACKGROUND: Mononuclear phagocytes, including monocyte-derived macrophages (MDMs) and microglia, contribute to infarct development as well as tissue repair in the postischemic brain. Here, we identify the origin and function of MDMs in the brain during poststroke repair processes. METHODS: Adult mice were subjected to transient middle cerebral artery occlusion. Longitudinal brain atrophy and secondary degeneration were evaluated during acute to recovery phases of stroke. Adoptive transfer of GFP+ splenocytes into asplenic mice was used to distinguish MDMs from resident microglia. Fluorescence beads were injected into stroked animals to examine phagocytic function. RESULTS: Progressive atrophy and neuronal degeneration in remote regions were observed in chronic stroke, which also was accompanied by MDM infiltration into the ipsilateral hemisphere. Compared with microglia, MDMs had significantly higher phagocytic activity. MDM trafficking and phagocytosis was spatiotemporally regulated with acute and prolonged infiltration into infarcted tissue, as well as delayed entry in remote areas such as the thalamus and substantia nigra. CONCLUSIONS: The stepwise and long-lasting involvement of MDMs at multiple poststroke stages shows that MDMs have a role in progressive stroke-induced injury and repair processes. These findings suggest that manipulating monocyte entry at different stroke stages may be an effective immune-based strategy to limit injury propagation in chronic stroke.
Authors: Roman Sankowski; Stefanie M Brendecke; Marta Joana Costa Jordão; Giuseppe Locatelli; Yi-Heng Tai; Tuan Leng Tay; Eva Schramm; Stephan Armbruster; Nora Hagemeyer; Olaf Groß; Dominic Mai; Özgün Çiçek; Thorsten Falk; Martin Kerschensteiner; Dominic Grün; Marco Prinz Journal: Science Date: 2019-01-25 Impact factor: 47.728
Authors: Joel V Faustino; Xia Wang; Cali E Johnson; Alexander Klibanov; Nikita Derugin; Michael F Wendland; Zinaida S Vexler Journal: J Neurosci Date: 2011-09-07 Impact factor: 6.167
Authors: Andrew D Greenhalgh; Juan G Zarruk; Luke M Healy; Sam J Baskar Jesudasan; Priya Jhelum; Christopher K Salmon; Albert Formanek; Matthew V Russo; Jack P Antel; Dorian B McGavern; Barry W McColl; Samuel David Journal: PLoS Biol Date: 2018-10-17 Impact factor: 8.029