Time-Dependent Changes in Microglia Transcriptional Networks Following Traumatic Brain Injury.
mice
microglia
neurodegeneration
neuroimmunology
neuroinflammation
transcriptome
traumatic brain injury
Journal
Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935
Informations de publication
Date de publication:
2019
2019
Historique:
received:
05
03
2019
accepted:
24
06
2019
entrez:
24
8
2019
pubmed:
24
8
2019
medline:
24
8
2019
Statut:
epublish
Résumé
The neuroinflammatory response to traumatic brain injury (TBI) is critical to both neurotoxicity and neuroprotection, and has been proposed as a potentially modifiable driver of secondary injury in animal and human studies. Attempts to broadly target immune activation have been unsuccessful in improving outcomes, in part because the precise cellular and molecular mechanisms driving injury and outcome at acute, subacute, and chronic time points after TBI remain poorly defined. Microglia play a critical role in neuroinflammation and their persistent activation may contribute to long-term functional deficits. Activated microglia are characterized by morphological transformation and transcriptomic changes associated with specific inflammatory states. We analyzed the temporal course of changes in inflammatory genes of microglia isolated from injured brains at 2, 14, and 60 days after controlled cortical impact (CCI) in mice, a well-established model of focal cerebral contusion. We identified a time dependent, injury-associated change in the microglial gene expression profile toward a reduced ability to sense tissue damage, perform housekeeping, and maintain homeostasis in the early stages following CCI, with recovery and transition to a specialized inflammatory state over time. This later state starts at 14 days post-injury and is characterized by a biphasic pattern of IFNγ, IL-4, and IL-10 gene expression changes, with concurrent proinflammatory and anti-inflammatory gene changes. Our transcriptomic data sets are an important step to understand microglial role in TBI pathogenesis at the molecular level and identify common pathways that affect outcome. More studies to evaluate gene expression at the single cell level and focusing on subacute and chronic timepoint are warranted.
Identifiants
pubmed: 31440141
doi: 10.3389/fncel.2019.00307
pmc: PMC6694299
doi:
Types de publication
Journal Article
Langues
eng
Pagination
307Subventions
Organisme : NINDS NIH HHS
ID : R01 NS092847
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG051506
Pays : United States
Références
J Immunol. 2000 Jun 15;164(12):6166-73
pubmed: 10843666
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9082-7
pubmed: 10922063
Neurobiol Aging. 2002 Jan-Feb;23(1):31-9
pubmed: 11755016
J Neurosci Res. 2002 Mar 1;67(5):646-63
pubmed: 11891777
Brain Res Mol Brain Res. 2002 Aug 15;104(2):148-58
pubmed: 12225869
J Neurochem. 2002 Sep;82(6):1311-29
pubmed: 12354279
Nat Neurosci. 2002 Dec;5(12):1288-93
pubmed: 12402041
J Biol Chem. 2003 Jan 17;278(3):1910-4
pubmed: 12417590
Nucleic Acids Res. 2003 Jan 1;31(1):258-61
pubmed: 12519996
Neuron. 2003 Dec 18;40(6):1133-45
pubmed: 14687548
Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8786-90
pubmed: 15173585
Forensic Sci Int. 2004 Dec 16;146(2-3):97-104
pubmed: 15542269
J Neurochem. 2005 Jan;92(2):417-32
pubmed: 15663489
J Neurosci. 2005 Jul 27;25(30):7040-7
pubmed: 16049180
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Neurobiol Dis. 2006 Apr;22(1):33-9
pubmed: 16386911
J Neuroinflammation. 2006 Feb 24;3:3
pubmed: 16504112
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7438-42
pubmed: 1651506
Am J Phys Med Rehabil. 2006 Apr;85(4):343-82
pubmed: 16554685
J Head Trauma Rehabil. 2006 Sep-Oct;21(5):375-8
pubmed: 16983222
J Neuroimmunol. 2007 Feb;183(1-2):1-6
pubmed: 17188367
J Cereb Blood Flow Metab. 2007 Nov;27(11):1806-18
pubmed: 17406655
Exp Neurol. 2007 Nov;208(1):145-58
pubmed: 17916353
J Cereb Blood Flow Metab. 2008 May;28(5):1030-9
pubmed: 18183030
Brain Inj. 2008 Feb;22(2):175-81
pubmed: 18240046
Nat Med. 2008 Jun;14(6):681-7
pubmed: 18516051
Immunol Rev. 2009 May;229(1):152-72
pubmed: 19426221
Neurosci Lett. 2009 Mar 27;453(1):68-72
pubmed: 19429018
J Cereb Blood Flow Metab. 2009 Sep;29(9):1503-16
pubmed: 19471279
Immunity. 2009 Jun 19;30(6):817-31
pubmed: 19481478
J Athl Train. 2009 Jul-Aug;44(4):434-48
pubmed: 19593427
Eur J Neurosci. 2009 Aug;30(3):385-96
pubmed: 19614750
Adv Exp Med Biol. 2009;647:174-85
pubmed: 19760074
Neurosci Lett. 2010 Mar 31;473(1):22-7
pubmed: 20152885
NeuroRehabilitation. 2010;26(3):239-55
pubmed: 20448314
Neurobiol Dis. 2010 Nov;40(2):394-403
pubmed: 20621186
Curr Neurovasc Res. 2011 Feb;8(1):44-51
pubmed: 21208160
Biochim Biophys Acta. 2011 May;1813(5):742-53
pubmed: 21295082
Exp Neurol. 2011 Jun;229(2):507-16
pubmed: 21515263
J Neuroinflammation. 2011 May 08;8:42
pubmed: 21549006
Eur J Neurosci. 2011 Jul;34(1):110-23
pubmed: 21623956
Ann Neurol. 2011 Sep;70(3):374-83
pubmed: 21710619
PLoS One. 2011;6(11):e27798
pubmed: 22110762
Bioinformatics. 2012 Jun 1;28(11):1546-8
pubmed: 22513995
J Neurotrauma. 2013 May 1;30(9):752-64
pubmed: 22913729
J Neuroinflammation. 2012 Oct 12;9:236
pubmed: 23061919
J Cereb Blood Flow Metab. 2013 Apr;33(4):524-31
pubmed: 23281425
J Cereb Blood Flow Metab. 2013 Aug;33(8):1182-9
pubmed: 23611870
J Immunol. 2013 Jun 15;190(12):6360-7
pubmed: 23667110
Cell Rep. 2013 Jul 25;4(2):385-401
pubmed: 23850290
Nat Neurosci. 2013 Dec;16(12):1896-905
pubmed: 24162652
Nat Neurosci. 2014 Jan;17(1):131-43
pubmed: 24316888
Immunity. 2013 Dec 12;39(6):1003-18
pubmed: 24332029
J Neuropathol Exp Neurol. 2014 Jan;73(1):14-29
pubmed: 24335533
J Neurotrauma. 2014 Apr 1;31(7):683-90
pubmed: 24344922
Biochem Pharmacol. 2014 Apr 15;88(4):495-8
pubmed: 24355566
Immunity. 2014 Feb 20;40(2):274-88
pubmed: 24530056
J Exp Med. 2014 Apr 7;211(4):595-604
pubmed: 24616379
Neurobiol Dis. 2015 Feb;74:58-65
pubmed: 25447235
Nat Rev Neurosci. 2015 May;16(5):249-63
pubmed: 25891508
Ann Transl Med. 2015 Jun;3(10):136
pubmed: 26207229
J Mol Neurosci. 2015 Oct;57(2):282-303
pubmed: 26319264
Cold Spring Harb Perspect Biol. 2015 Sep 09;8(1):a020560
pubmed: 26354893
Trends Neurosci. 2015 Oct;38(10):609-620
pubmed: 26442695
J Neurotrauma. 2016 Oct 1;33(19):1732-1750
pubmed: 26486881
Front Cell Neurosci. 2015 Oct 28;9:426
pubmed: 26578886
Brain Behav Immun. 2016 May;54:95-109
pubmed: 26774527
PLoS One. 2016 Jan 25;11(1):e0148001
pubmed: 26808663
Int J Mol Sci. 2016 Feb 06;17(2):216
pubmed: 26861311
BMC Genomics. 2016 Feb 24;17:130
pubmed: 26912237
J Neurotrauma. 2017 Jan 15;34(2):423-435
pubmed: 26976047
J Neuroinflammation. 2016 Apr 18;13(1):80
pubmed: 27090212
Nucleic Acids Res. 2016 Nov 16;44(20):e151
pubmed: 27471031
Sci Rep. 2016 Aug 17;6:31570
pubmed: 27530814
PLoS One. 2016 Sep 06;11(9):e0162497
pubmed: 27598576
Nucleic Acids Res. 2017 Jan 4;45(D1):D362-D368
pubmed: 27924014
Front Immunol. 2016 Dec 05;7:556
pubmed: 27994591
PLoS One. 2016 Dec 28;11(12):e0167677
pubmed: 28030563
Nat Rev Neurol. 2017 Mar;13(3):171-191
pubmed: 28186177
Glia. 2017 Sep;65(9):1504-1520
pubmed: 28618077
Front Aging Neurosci. 2017 Jun 28;9:208
pubmed: 28701948
Nat Rev Neurol. 2017 Sep;13(9):572
pubmed: 28776601
Front Aging Neurosci. 2017 Jul 21;9:227
pubmed: 28785215
Neuron. 2017 Sep 13;95(6):1246-1265
pubmed: 28910616
Front Immunol. 2017 Dec 12;8:1791
pubmed: 29312317
J Neuroinflammation. 2018 Jan 22;15(1):24
pubmed: 29357880
J Neurosci. 2018 Mar 7;38(10):2519-2532
pubmed: 29437855
J Neurotrauma. 2019 Jan 15;36(2):370-379
pubmed: 29768967
J Neuroinflammation. 2018 May 17;15(1):146
pubmed: 29776443
Nat Commun. 2018 Sep 25;9(1):3894
pubmed: 30254269
Nat Neurosci. 2018 Oct;21(10):1359-1369
pubmed: 30258234
Acta Neuropathol Commun. 2018 Nov 26;6(1):129
pubmed: 30477578
Front Immunol. 2018 Nov 27;9:2751
pubmed: 30538705
Circ Res. 2019 Jan 18;124(2):279-291
pubmed: 30582456
Cell. 2019 Feb 21;176(5):1143-1157.e13
pubmed: 30794775
J Neurotrauma. 1994 Oct;11(5):499-506
pubmed: 7861443
Neuroreport. 1997 Dec 1;8(17):3829-32
pubmed: 9427378
J Neurotrauma. 1998 Aug;15(8):599-614
pubmed: 9726259