Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner

Cell
Emily F WillisJana Vukovic

Abstract

Cognitive dysfunction and reactive microglia are hallmarks of traumatic brain injury (TBI), yet whether these cells contribute to cognitive deficits and secondary inflammatory pathology remains poorly understood. Here, we show that removal of microglia from the mouse brain has little effect on the outcome of TBI, but inducing the turnover of these cells through either pharmacologic or genetic approaches can yield a neuroprotective microglial phenotype that profoundly aids recovery. The beneficial effects of these repopulating microglia are critically dependent on interleukin-6 (IL-6) trans-signaling via the soluble IL-6 receptor (IL-6R) and robustly support adult neurogenesis, specifically by augmenting the survival of newborn neurons that directly support cognitive function. We conclude that microglia in the mammalian brain can be manipulated to adopt a neuroprotective and pro-regenerative phenotype that can aid repair and alleviate the cognitive deficits arising from brain injury.

References

Feb 1, 1997·Nature Biotechnology·M FischerS Rose-John
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·P MärzS Rose-John
Dec 20, 2000·European Journal of Biochemistry·T JostockS Rose-John
Aug 3, 2002·The Journal of Physiology·Lars NyboNiels H Secher
May 17, 2005·Nature Neuroscience·Dimitrios DavalosWen-Biao Gan
Oct 13, 2006·Journal of Leukocyte Biology·Marco E Bianchi
Mar 3, 2007·Genesis : the Journal of Genetics and Development·Cara K BradleyJ Anke M van Eekelen
Oct 30, 2007·Nature Neuroscience·Uwe-Karsten Hanisch, Helmut Kettenmann
Nov 8, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Knut BiberH W G M Boddeke
Jun 24, 2008·Brain : a Journal of Neurology·H NeumannR J M Franklin
Apr 30, 2011·Physiological Reviews·Helmut KettenmannAlexei Verkhratsky
Jul 23, 2011·Science·Rosa C PaolicelliCornelius T Gross
Apr 28, 2012·Bioinformatics·David S DeLucaGad Getz
May 4, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rebecca D HodgeRobert F Hevner
May 11, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jana VukovicPerry F Bartlett
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Apr 12, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jana VukovicPerry F Bartlett
May 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·James W GodwinNadia A Rosenthal
Dec 10, 2013·Nature Neuroscience·Oleg ButovskyHoward L Weiner
Feb 14, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Iain L CampbellJuan Hidalgo
Jul 15, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rachel A RiceKim N Green
Sep 29, 2015·Journal of Neurotrauma·Xiaoting WangJinhui Chen
Feb 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Mariko L BennettBen A Barres
Mar 27, 2016·Biochimica Et Biophysica Acta·Michelle RothaugStefan Rose-John
May 28, 2016·International Neurourology Journal·Heeok HongHeh-In Im
Sep 23, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ali ErtürkMorgan Sheng
Nov 1, 2016·Nature Immunology·Anne ButtgereitMelanie Greter
Dec 14, 2016·Annual Review of Physiology·Susanne A WolfHelmut Kettenmann
Jan 19, 2017·Nature·Shane A LiddelowBen A Barres
Feb 12, 2017·Nature Reviews. Neurology·Dennis W SimonPatrick M Kochanek
Mar 10, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Wei-Na JinQiang Liu

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Citations

Jun 27, 2020·Immunological Reviews·Hannah E Ennerfelt, John R Lukens
Jul 3, 2020·Frontiers in Cell and Developmental Biology·Luís A RochaAntonio J Salgado
Sep 12, 2020·Nature Communications·Ashley C BolteJohn R Lukens
Aug 31, 2020·F1000Research·Stefan Rose-John
Sep 23, 2020·International Journal of Molecular Sciences·Jinming HanRobert A Harris
Aug 28, 2020·Scandinavian Journal of Immunology·Trevor OwensReza Khorooshi
Oct 8, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Xiaoming Hu
Nov 1, 2020·Translational Stroke Research·Junxuan LyuJun Chen
Nov 3, 2020·Frontiers in Aging Neuroscience·Ruichan JiangHailiang Liu
Dec 9, 2020·Acta Neuropathologica Communications·Jinming HanRobert A Harris
Jan 9, 2021·Molecular Neurobiology·Hui GaoHaiwei Xu
Dec 20, 2020·Lancet Neurology·Danielle K Sandsmark, Ramon Diaz-Arrastia
Jan 20, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Sandrine Bourgeois-TardifAlexander G Weil
Jan 23, 2021·Npj Regenerative Medicine·Daniel Cortes, Martin F Pera
Nov 17, 2020·Frontiers in Neurology·Emily Ross-MunroDavid W Walker
Nov 19, 2020·International Journal of Molecular Sciences·Jinming HanRobert A Harris
Feb 9, 2021·Frontiers in Cellular Neuroscience·Sana ChintamenSteven G Kernie
Nov 25, 2020·Neural Regeneration Research·Mariam RizkZhi Zhang
Mar 3, 2021·CNS Neuroscience & Therapeutics·Junxuan LyuXiaoyan Jiang
Mar 2, 2021·Neural Regeneration Research·David Graykowski, Eiron Cudaback
Mar 12, 2021·Acta Neuropathologica Communications·Marta CelorrioStuart H Friess
Nov 13, 2020·Neurochemistry International·Kazuya MiyanishiJunya Tanaka
Dec 2, 2020·Neuroscience Letters·Maria Serena PaladiniSusanna Rosi
Apr 7, 2021·The American Journal of Psychiatry·Victor M CastroRoy H Perlis
May 5, 2021·Trends in Immunology·Ashley C Bolte, John R Lukens
May 29, 2021·Seminars in Immunopathology·Dirk Schmidt-ArrasStefan Rose-John
Jun 9, 2021·The Journal of Experimental Medicine·Maud GratuzeDavid M Holtzman
May 25, 2021·Epilepsy Currents·Nigel C Jones
May 23, 2021·Cytokine·Stefan Rose-John
Jun 11, 2021·Frontiers in Cell and Developmental Biology·Andrei TurkinFriederike Klempin

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