Neurotoxic responses by microglia elicited by excitotoxic injury in the mouse hippocampus

Current Biology : CB
A D Rogove, S E Tsirka

Abstract

Injury to the brain induces dramatic local changes in gene expression, cellular morphology and behavior. Activation of microglial cells occurs as an early event after central nervous system (CNS) injury, but it has not been determined whether such activation plays a causal role in neuronal death. We have investigated this question using an excitotoxin-mediated brain injury model system, in conjunction with an endogenous peptide factor (macrophage/microglial inhibiting factor, MIF) that ablates microglial contribution to the cascade. Using MIF, we inhibited the microglial activation that normally follows excitotoxic injury. In cell culture studies, we found that such inhibition blocked the rapid release of microglia-derived tissue plasminogen activator (tPA), an extracellular serine protease made by both neurons and microglia, which we had previously identified as mediating a critical step in excitotoxin-induced neuronal death. Finally, infusion of MIF into the mouse brain prior to excitotoxic insult resulted in the protection of neurons from cell death. Our results demonstrate that microglia undertake a neurotoxic role when excitotoxic injury occurs in the CNS. They also suggest that the tPA released from microglia has a critic...Continue Reading

References

Sep 1, 1990·Trends in Pharmacological Sciences·B Meldrum, J Garthwaite
Nov 2, 1987·FEBS Letters·C A Colton, D L Gilbert
Aug 1, 1995·Neuropathology and Applied Neurobiology·J GehrmannG W Kreutzberg
Aug 1, 1996·Trends in Neurosciences·G W Kreutzberg
Nov 14, 1996·Nature·S E TsirkaS Strickland
Jan 1, 1996·Acta Neuropathologica·S C Zhang, S Fedoroff
Mar 3, 1997·Neuroreport·K Kumar, A T Evans

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Citations

Feb 27, 2001·Journal of Neuroscience Research·M P Flavin, G Zhao
Jan 19, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Ashley D ReynoldsHoward E Gendelman
Apr 15, 2004·Molecular and Cellular Neurosciences·Mónica Fernández-MonrealDenis Vivien
Jun 25, 2003·Experimental Neurology·Karin BorgesRaymond Dingledine
Jul 7, 1999·Neuroscience and Biobehavioral Reviews·E Gahtan, J B Overmier
Sep 25, 2002·The European Journal of Neuroscience·Hadas SchoriMichal Schwartz
May 18, 2011·The Journal of Experimental Medicine·Fernando CorreaFabian Docagne
Jul 21, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·Ruiping ZhangPiu Chan
Dec 3, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·R T HayM S Rodriguez
Feb 9, 2013·PloS One·Kyungmin JiStella E Tsirka
May 14, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jaime EmmetsbergerStella E Tsirka
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·J YrjänheikkiJ Koistinaho
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·M Kaul, S A Lipton
Dec 25, 2010·Neurochemical Research·Bárbara TagliariAngela T S Wyse
Aug 6, 1999·Current Eye Research·K S KunertC K Dorey
Jan 20, 2010·Journal of Neuropathology and Experimental Neurology·Heike BeckKarl H Plate
Apr 7, 2010·Neuropharmacology·Dong Hyun KimJong Hoon Ryu
Apr 13, 2010·Neurobiology of Disease·Martine M MirrioneStella E Tsirka
Jul 29, 2015·Data in Brief·Philip ChuJoshua C Brumberg
Apr 8, 2009·Neurobiology of Aging·Elaine LeungChangiz Geula
Jan 5, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·S KoponenJ Koistinaho
Dec 10, 2015·Frontiers in Cellular Neuroscience·Christina StefanitschLinda Fredriksson
Sep 29, 2009·Journal of Neurochemistry·D Allan Butterfield, Miranda L Bader Lange
Feb 14, 2004·Molecular and Cellular Neurosciences·Mustafa M Siddiq, Stella E Tsirka
Sep 17, 2013·Journal of Neurochemistry·Jillian C NissenStella E Tsirka
Jan 26, 2011·Glia·Haiyan ZhaiStella E Tsirka

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