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Cited by 657Neuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury and Neurovascular DisturbancesSpinal Cord Injury Research

Role of Microglia in Neurotrauma

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Loane, David J., Byrnes, Kimberly R.·2010·Neurotherapeutics
DOI 10.1016/j.nurt.2010.07.002PMC PMC2948548
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Abstract

Microglia are the primary mediators of the immune defense system of the CNS and are integral to the subsequent inflammatory response. The role of microglia in the injured CNS is under scrutiny, as research has begun to fully explore how postinjury inflammation contributes to secondary damage and recovery of function. Whether microglia are good or bad is under debate, with strong support for a dual role or differential activation of microglia. Microglia release a number of factors that modulate secondary injury and recovery after injury, including pro- and anti-inflammatory cytokines, chemokines, nitric oxide, prostaglandins, growth factors, and superoxide species. Here we review experimental work on the complex and varied responses of microglia in terms of both detrimental and beneficial effects. Addressed in addition are the effects of microglial activation in two examples of CNS injury: spinal cord and traumatic brain injury. Microglial activation is integral to the response of CNS tissue to injury. In that light, future research is needed to focus on clarifying the signals and mechanisms by which microglia can be guided to promote optimal functional recovery.

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  • The TGF-β signaling components are consistent with partial restoration of homeostatic regulatory pathways.

    “Notably, components of the TGF-β signaling axis were represented among the regulated genes, consistent with partial restoration of homeostatic regulatory pathways [150–152].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [150]

    The “Beneficial responses of microglial activation” section describes TGF-β as anti-inflammatory and says it inhibits microglial activation, supporting a regulatory role. The paper does not show that regulated TGF-β signaling genes indicate partial restoration of homeostatic pathways; that interpretation goes beyond its findings. Our copy provides no page numbers for these passages. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Components of the TGF-β signaling axis were represented among the regulated genes in microglia after tau ablation.

    “Notably, components of the TGF-β signaling axis were represented among the regulated genes, consistent with partial restoration of homeostatic regulatory pathways [150–152].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [150]

    The sections on traumatic brain injury and beneficial microglial responses discuss TGF-β after injury and its anti-inflammatory effects, but not tau ablation. Searches for tau ablation, regulated genes, and homeostatic pathways found no passage addressing the attributed finding. Page numbers are not available in our copy. (LLM, conf=0.76)

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Research works printed but not linked: 184

  1. [3]Graeber MB Streit WJ Microglia: biology and pathology. Acta Neuropathol 2009 20012873
  2. [4]Weinstein JR Koerner IP Moller T Microglia in ischemic brain injury. Future Neurol 2010 5 227 246 20401171 PMC2853969
  3. [5]Yadav A Collman RG CNS inflammation and macrophage/microglial biology associated with HIV-1 infection. J Neuroimmune Pharmacol 2009 4 430 447 19768553 PMC5935112
  4. [6]Jack C Ruffini F Bar-Or A Antel JP Microglia and multiple sclerosis. J Neurosci Res 2005 81 363 373 15948188
  5. [7]Moisse K Strong MJ Innate immunity in amyotrophic lateral sclerosis. Biochim Biophys Acta 2006 1762 1083 1093 16624536
  6. [8]Streit WJ Conde JR Fendrick SE Flanary BE Mariani CL Role of microglia in the central nervous system's immune response. Neurol Res 2005 27 685 691 16197805
  7. [11]Vilhardt F Microglia: phagocyte and glia cell. Int J Biochem Cell Biol 2005 37 17 21 15381143
  8. [13]Liu GJ Nagarajah R Banati RB Bennett MR Glutamate induces directed chemotaxis of microglia. Eur J Neurosci 2009 29 1108 1118 19302147
  9. [14]Streit WJ Walter SA Pennell NA Reactive microgliosis. Prog Neurobiol 1999 57 563 581 10221782
  10. [15]Shaked I Tchoresh D Gersner R Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J Neurochem 2005 92 997 1009 15715651
  11. [16]Stirling DP Yong VW Dynamics of the inflammatory response after murine spinal cord injury revealed by flow cytometry. J Neurosci Res 2008 18438914
  12. [17]Lalancette-Hebert M Gowing G Simard A Weng YC Kriz J Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J Neurosci 2007 27 2596 2605 17344397 PMC6672496
  13. [18]Enose Y Destache CJ Mack AL Proteomic fingerprints distinguish microglia, bone marrow, and spleen macrophage populations. Glia 2005 51 161 172 15795904
  14. [19]Albright AV Gonzalez-Scarano F Microarray analysis of activated mixed glial (microglia) and monocyte-derived macrophage gene expression. J Neuroimmunol 2004 157 27 38 15579277
  15. [20]Milligan CE Levitt P Cunningham TJ Brain macrophages and microglia respond differently to lesions of the developing and adult visual system. J Comp Neurol 1991 314 136 146 1797869
  16. [22]Gao HM Hong JS Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 2008 PMC4794280 18599350
  17. [23]Griffin WS Sheng JG Royston MC Glial-neuronal interactions in Alzheimer's disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol 1998 8 65 72 9458167 PMC8098321
  18. [24]Dean JM Wang X Kaindl AM Microglial MyD88 signaling regulates acute neuronal toxicity of LPS-stimulated microglia in vitro. Brain Behav Immun 2009 19903519
  19. [26]Pinteaux-Jones F Sevastou IG Fry VA Heales S Baker D Pocock JM Myelin-induced microglial neurotoxicity can be controlled by microglial metabotropic glutamate receptors. J Neurochem 2008 18419765
  20. [27]Fang KM Yang CS Sun SH Tzeng SF Microglial phagocytosis attenuated by short-term exposure to exogenous ATP through P2X receptor action. J Neurochem 2009 111 1225 1237 19860838
  21. [29]Qin L Liu Y Cooper C Liu B Wilson B Hong JS Microglia enhance beta-amyloid peptide-induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species. J Neurochem 2002 83 973 983 12421370
  22. [30]Combs CK Johnson DE Karlo JC Cannady SB Landreth GE Inflammatory mechanisms in Alzheimer's disease: inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists. J Neurosci 2000 20 558 567 10632585 PMC6772401
  23. [31]Pais TF Figueiredo C Peixoto R Braz MH Chatterjee S Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathway. J Neuroinflammation 2008 5 43 18844999 PMC2572162
  24. [32]Knoch ME Hartnett KA Hara H Kandler K Aizenman E Microglia induce neurotoxicity via intraneuronal Zn(2+) release and a K(+) current surge. Glia 2008 56 89 96 17955552 PMC2561170
  25. [33]Gao HM Liu B Zhang W Hong JS Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson's disease. FASEB J 2003 17 1954 1956 12897068
  26. [34]Gao HM Liu B Hong JS Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 2003 23 6181 6187 12867501 PMC6740554
  27. [35]Wu DC Teismann P Tieu K NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci U S A 2003 100 6145 6150 12721370 PMC156340
  28. [36]Loane DJ Stoica BA Pajoohesh-Ganji A Byrnes KR Faden AI Activation of metabotropic glutamate receptor 5 modulates microglial reactivity and neurotoxicity by inhibiting NADPH oxidase. J Biol Chem 2009 284 15629 15639 19364772 PMC2708859
  29. [37]Qin L Liu Y Wang T NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem 2004 279 1415 1421 14578353
  30. [38]DeLeo FR Quinn MT Assembly of the phagocyte NADPH oxidase: molecular interaction of oxidase proteins. J Leukoc Biol 1996 60 677 691 8975869
  31. [39]Pawate S Shen Q Fan F Bhat NR Redox regulation of glial inflammatory response to lipopolysaccharide and interferongamma. J Neurosci Res 2004 77 540 551 15264224
  32. [40]Chung JY Choi JH Lee CH Comparison of ionized calcium-binding adapter molecule 1-immunoreactive microglia in the spinal cord between young adult and aged dogs. Neurochem Res 2009 20012688
  33. [41]Godbout JP Chen J Abraham J Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J 2005 19 1329 1331 15919760
  34. [42]Lynch AM Loane DJ Minogue AM Eicosapentaenoic acid confers neuroprotection in the amyloid-beta challenged aged hippocampus. Neurobiol Aging 2007 28 845 855 16714069
  35. [43]Gelinas DS McLaurin J PPAR-alpha expression inversely correlates with inflammatory cytokines IL-1beta and TNF-alpha in aging rats. Neurochem Res 2005 30 1369 1375 16341933
  36. [44]Godbout JP Johnson RW Interleukin-6 in the aging brain. J Neuroimmunol 2004 147 141 144 14741447
  37. [45]Murray CA Lynch MA Dietary supplementation with vitamin E reverses the age-related deficit in long term potentiation in dentate gyrus. J Biol Chem 1998 273 12161 12168 9575163
  38. [46]Conde JR Streit WJ Microglia in the aging brain. J Neuropathol Exp Neurol 2006 65 199 203 16651881
  39. [47]Baune BT Ponath G Rothermundt M Roesler A Berger K Association between cytokines and cerebral MRI changes in the aging brain. J Geriatr Psychiatry Neurol 2009 22 23 34 19196630
  40. [48]Li J Baud O Vartanian T Volpe JJ Rosenberg PA Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes. Proc Natl Acad Sci U S A 2005 102 9936 9941 15998743 PMC1174990
  41. [49]Li J Ramenaden ER Peng J Koito H Volpe JJ Rosenberg PA Tumor necrosis factor alpha mediates lipopolysaccharide-induced microglial toxicity to developing oligodendrocytes when astrocytes are present. J Neurosci 2008 28 5321 5330 18480288 PMC2677805
  42. [50]Block ML Hong JS Chronic microglial activation and progressive dopaminergic neurotoxicity. Biochem Soc Trans 2007 35 1127 1132 17956294
  43. [52]Fraser DA Pisalyaput K Tenner AJ C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production. J Neurochem 2009 PMC2809134 19919576
  44. [53]Li L Lu J Tay SS Moochhala SM He BP The function of microglia, either neuroprotection or neurotoxicity, is determined by the equilibrium among factors released from activated microglia in vitro. Brain Res 2007 1159 8 17 17572395
  45. [54]Kigerl KA Gensel JC Ankeny DP Alexander JK Donnelly DJ Popovich PG Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 2009 29 13435 13444 19864556 PMC2788152
  46. [55]Colton CA Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 2009 4 399 418 19655259 PMC2773116
  47. [56]Colton CA Mott RT Sharpe H Xu Q Van Nostrand WE Vitek MP Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. J Neuroinflammation 2006 3 27 17005052 PMC1609108
  48. [57]Butovsky O Talpalar AE Ben-Yaakov K Schwartz M Activation of microglia by aggregated beta-amyloid or lipopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-gamma and IL-4 render them protective. Mol Cell Neurosci 2005 29 381 393 15890528
  49. [58]Lyons A Griffin RJ Costelloe CE Clarke RM Lynch MA IL-4 attenuates the neuroinflammation induced by amyloid-beta in vivo and in vitro. J Neurochem 2007 101 771 781 17250684
  50. [59]Aloisi F De Simone R Columba-Cabezas S Levi G Opposite effects of interferon-gamma and prostaglandin E2 on tumor necrosis factor and interleukin-10 production in microglia: a regulatory loop controlling microglia pro- and anti-inflammatory activities. J Neurosci Res 1999 56 571 580 10374812
  51. [60]Liu JS Amaral TD Brosnan CF Lee SC IFNs are critical regulators of IL-1 receptor antagonist and IL-1 expression in human microglia. J Immunol 1998 161 1989 1996 9712071
  52. [61]Kiefer R Schweitzer T Jung S Toyka KV Hartung HP Sequential expression of transforming growth factor-beta1 by T-cells, macrophages, and microglia in rat spinal cord during autoimmune inflammation. J Neuropathol Exp Neurol 1998 57 385 395 9596409
  53. [62]Elkabes S DiCicco-Bloom EM Black IB Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 1996 16 2508 2521 8786427 PMC6578768
  54. [63]Allan SM Tyrrell PJ Rothwell NJ Interleukin-1 and neuronal injury. Nat Rev Immunol 2005 5 629 640 16034365
  55. [64]O'Keefe GM Nguyen VT Benveniste EN Class II transactivator and class II MHC gene expression in microglia: modulation by the cytokines TGF-beta, IL-4, IL-13 and IL-10. Eur J Immunol 1999 29 1275 1285 10229095
  56. [65]Frei K Lins H Schwerdel C Fontana A Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed. J Immunol 1994 152 2720 2728 8144879
  57. [66]Polazzi E Altamira LE Eleuteri S Neuroprotection of microglial conditioned medium on 6-hydroxydopamine-induced neuronal death: role of transforming growth factor beta-2. J Neurochem 2009 110 545 556 19457129
  58. [67]Lai AY Todd KG Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury. Glia 2008 56 259 270 18069670
  59. [68]Pinteaux E Rothwell NJ Boutin H Neuroprotective actions of endogenous interleukin-1 receptor antagonist (IL-1ra) are mediated by glia. Glia 2006 53 551 556 16374779
  60. [69]Roy A Liu X Pahan K Myelin basic protein-primed T cells induce neurotrophins in glial cells via alphavbeta3 [corrected] integrin. J Biol Chem 2007 282 32222 32232 17823123 PMC2637617
  61. [70]Bai B Song W Ji Y Microglia and microglia-like cell differentiated from DC inhibit CD4 T cell proliferation. PLoS One 2009 4 e7869 19924241 PMC2773419
  62. [71]Neumann J Sauerzweig S Ronicke R Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege. J Neurosci 2008 28 5965 5975 18524901 PMC6670327
  63. [72]Bao F Dekaban GA Weaver LC Anti-CD11d antibody treatment reduces free radical formation and cell death in the injured spinal cord of rats. J Neurochem 2005 94 1361 1373 15992367
  64. [73]Hausmann ON Post-traumatic inflammation following spinal cord injury. Spinal Cord 2003 41 369 378 12815368
  65. [74]Fitch MT Doller C Combs CK Landreth GE Silver J Cellular and molecular mechanisms of glial scarring and progressive cavitation: In vivo and in vitro analysis of inflammation-induced secondary injury after cns trauma. J Neurosci 1999 19 8182 8198 10493720 PMC6783021
  66. [75]Dusart I Schwab ME Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J Neurosci 1994 6 712 724 8075816
  67. [76]Koshinaga M Whittemore SR The temporal and spatial activation of microglia in fiber tracts undergoing anterograde and retrograde degeneration following spinal cord lesion. J Neurotrauma 1995 12 209 222 7629867
  68. [77]Bareyre FM Schwab ME Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci 2003 26 555 563 14522149
  69. [78]Popovich PG Guan Z McGaughy V Fisher L Hickey WF Basso DM The neuropathological and behavioral consequences of intraspinal microglial/macrophage activation. J Neuropathol Exp Neurol 2002 61 623 633 12125741
  70. [79]Keane RW Davis AR Dietrich WD Inflammatory and apoptotic signaling after spinal cord injury. J Neurotrauma 2006 23 335 344 16629620
  71. [80]Wang X Arcuino G Takano T P2X7 receptor inhibition improves recovery after spinal cord injury. Nat Med 2004 10 821 827 15258577
  72. [81]Schwab JM Brechtel K Nguyen TD Schluesener HJ Persistent accumulation of cyclooxygenase-1 (COX-1) expressing microglia/macrophages and upregulation by endothelium following spinal cord injury. J Neuroimmunol 2000 111 122 130 11063829
  73. [82]Schmitt AB Buss A Breuer S Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response. Acta Neuropathol (Berl) 2000 100 528 536 11045675
  74. [83]Popovich PG van Rooijen N Hickey WF Preidis G McGaughy V Hematogenous macrophages express CD8 and distribute to regions of lesion cavitation after spinal cord injury. Exp Neurol 2003 182 275 287 12895439
  75. [84]Bruce-Keller AJ Microglial-neuronal interactions in synaptic damage and recovery. J Neurosci Res 1999 58 191 201 10491582
  76. [85]Aggarwal BB Samanta A Feldman M Oppenheim JJ Feldman M TNF alpha. Cytokine Reference. A Compendium of Cytokines and Other Mediators of Host Defense 2001 413 434 Academic Press, Inc. San Diego
  77. [86]Benveniste EN Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am J Physiol 1992 263 C1 16 1636671
  78. [87]Bartholdi D Schwab ME Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: an in situ hybridization study. Eur J Neurosci 1997 9 1422 1438 9240400
  79. [88]Hayashi M Ueyama T Nemoto K Tamaki T Senba E Sequential mRNA expression for immediate early genes, cytokines, and neurotrophins in spinal cord injury. J Neurotrauma 2000 17 203 218 10757326
  80. [89]Streit WJ Semple-Rowland SL Hurley SD Miller RC Popovich PG Stokes BT Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis. Exp Neurol 1998 152 74 87 9682014
  81. [90]Li JM Fan LM Christie MR Shah AM Acute tumor necrosis factor alpha signaling via NADPH oxidase in microvascular endothelial cells: role of p47phox phosphorylation and binding to TRAF4. Mol Cell Biol 2005 25 2320 2330 15743827 PMC1061612
  82. [91]Zou JY Crews FT TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition. Brain Res 2005 1034 11 24 15713255
  83. [92]Di Giovanni S Knoblach SM Brandoli C Aden SA Hoffman EP Faden AI Gene profiling in spinal cord injury shows role of cell cycle in neuronal death. Ann Neurol 2003 53 454 468 12666113
  84. [93]De Biase A Knoblach SM Di Giovanni S Gene expression profiling of experimental traumatic spinal cord injury as a function of distance from impact site and injury severity. Physiol Genomics 2005 22 368 381 15942019
  85. [94]Aimone JB Leasure JL Perreau VM Thallmair M Spatial and temporal gene expression profiling of the contused rat spinal cord. Exp Neurol 2004 189 204 221 15380473
  86. [95]Carmel JB Galante A Soteropoulos P Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss. Physiol Genomics 2001 7 201 213 11773606
  87. [96]Byrnes KR Garay J Di Giovanni S Expression of two temporally distinct microglia-related gene clusters after spinal cord injury. Glia 2006 53 420 433 16345062
  88. [97]Zai LJ Wrathall JR Cell proliferation and replacement following contusive spinal cord injury. Glia 2005 50 247 257 15739189
  89. [98]Carlson SL Parrish ME Springer JE Doty K Dossett L Acute inflammatory response in spinal cord following impact injury. Exp Neurol 1998 151 77 88 9582256
  90. [99]Popovich PG Wei P Stokes BT Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol 1997 377 443 464 8989657
  91. [100]Beck KD Nguyen HX Galvan MD Salazar DL Woodruff TM Anderson AJ Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain 133 433 447 20085927 PMC2858013
  92. [101]Aloisi F Immune function of microglia. Glia 2001 36 165 179 11596125
  93. [102]Popovich PG Hickey WF Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord. J Neuropathol Exp Neurol 2001 60 676 685 11444796
  94. [103]Yang L Jones NR Blumbergs PC Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat. J Clin Neurosci 2005 12 276 284 15851082
  95. [104]Popovich PG Horner PJ Mullin BB Stokes BT A quantitative spatial analysis of the blood-spinal cord barrier. I. Permeability changes after experimental spinal contusion injury. Exp Neurol 1996 142 258 275 8934558
  96. [105]Shechter R London A Varol C Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med 2009 6 e1000113 19636355 PMC2707628
  97. [106]Vaziri ND Lee YS Lin CY Lin VW Sindhu RK NAD(P)H oxidase, superoxide dismutase, catalase, glutathione peroxidase and nitric oxide synthase expression in subacute spinal cord injury. Brain Res 2004 995 76 83 14644473
  98. [107]Liu D Bao F Prough DS Dewitt DS Peroxynitrite generated at the level produced by spinal cord injury induces peroxidation of membrane phospholipids in normal rat cord: reduction by a metalloporphyrin. J Neurotrauma 2005 22 1123 1133 16238488
  99. [108]Bao F Liu D Peroxynitrite generated in the rat spinal cord induces neuron death and neurological deficits. Neuroscience 2002 115 839 849 12435422
  100. [109]Xu M Wai-Cheong Yip G Gan LT Ng YK Distinct roles of oxidative stress and antioxidants in the nucleus dorsalis and red nucleus following spinal cord hemisection. Brain Res 2005 1055 137 142 16095570
  101. [110]Wu J Yoo S Wilcock D Interaction of NG2(+) glial progenitors and microglia/macrophages from the injured spinal cord. Glia 2009 PMC2807472 19780197
  102. [111]Horn KP Busch SA Hawthorne AL van Rooijen N Silver J Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. J Neurosci 2008 28 9330 9341 18799667 PMC2567141
  103. [112]Rolls A Shechter R London A Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med 2008 5 e171 18715114 PMC2517615
  104. [113]Slepko N Levi G Progressive activation of adult microglial cells in vitro. Glia 1996 16 241 246 8833194
  105. [114]Zhang KH Xiao HS Lu PH Differential gene expression after complete spinal cord transection in adult rats: an analysis focused on a subchronic post-injury stage. Neuroscience 2004 128 375 388 15350649
  106. [115]Reichert F Rotshenker S Deficient activation of microglia during optic nerve degeneration. J Neuroimmunol 1996 70 153 161 8898724
  107. [116]Povlishock JT Katz DI Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil 2005 20 76 94 15668572
  108. [117]McIntosh TK Saatman KE Raghupathi R The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol Appl Neurobiol 1998 24 251 267 9775390
  109. [118]Streit WJ The role of microglia in brain injury. Neurotoxicology 1996 17 671 678 9086488
  110. [119]Giordana MT Attanasio A Cavalla P Migheli A Vigliani MC Schiffer D Reactive cell proliferation and microglia following injury to the rat brain. Neuropathol Appl Neurobiol 1994 20 163 174 8072646
  111. [121]Engel S Schluesener H Mittelbronn M Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14. Acta Neuropathol 2000 100 313 322 10965802
  112. [122]Beschorner R Nguyen TD Gozalan F CD14 expression by activated parenchymal microglia/macrophages and infiltrating monocytes following human traumatic brain injury. Acta Neuropathol 2002 103 541 549 12012085
  113. [123]Gentleman SM Leclercq PD Moyes L Long-term intracerebral inflammatory response after traumatic brain injury. Forensic Sci Int 2004 146 97 104 15542269
  114. [124]Csuka E Hans VH Ammann E Trentz O Kossmann T Morganti-Kossmann MC Cell activation and inflammatory response following traumatic axonal injury in the rat. Neuroreport 2000 11 2587 2590 10943727
  115. [125]Maeda J Higuchi M Inaji M Phase-dependent roles of reactive microglia and astrocytes in nervous system injury as delineated by imaging of peripheral benzodiazepine receptor. Brain Res 2007 1157 100 111 17540348
  116. [126]Raghavendra Rao VL Dogan A Bowen KK Dempsey RJ Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus. Exp Neurol 2000 161 102 114 10683277
  117. [127]Raghavendra Rao VL Dhodda VK Song G Bowen KK Dempsey RJ Traumatic brain injury-induced acute gene expression changes in rat cerebral cortex identified by GeneChip analysis. J Neurosci Res 2003 71 208 219 12503083
  118. [128]Natale JE Ahmed F Cernak I Stoica B Faden AI Gene expression profile changes are commonly modulated across models and species after traumatic brain injury. J Neurotrauma 2003 20 907 927 14588109
  119. [129]Kobori N Clifton GL Dash P Altered expression of novel genes in the cerebral cortex following experimental brain injury. Brain Res Mol Brain Res 2002 104 148 158 12225869
  120. [130]Israelsson C Bengtsson H Kylberg A Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury. J Neurotrauma 2008 25 959 974 18665806
  121. [131]Lu KT Wang YW Yang JT Yang YL Chen HI Effect of interleukin-1 on traumatic brain injury-induced damage to hippocampal neurons. J Neurotrauma 2005 22 885 895 16083355
  122. [132]Lu KT Wang YW Wo YY Yang YL Extracellular signal-regulated kinase-mediated IL-1-induced cortical neuron damage during traumatic brain injury. Neurosci Lett 2005 386 40 45 16024175
  123. [133]Fan L Young PR Barone FC Feuerstein GZ Smith DH McIntosh TK Experimental brain injury induces expression of interleukin-1 beta mRNA in the rat brain. Brain Res Mol Brain Res 1995 30 125 130 7609633
  124. [134]Pinteaux E Parker LC Rothwell NJ Luheshi GN Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells. J Neurochem 2002 83 754 763 12421347
  125. [135]Rothwell N Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential. Brain Behav Immun 2003 17 152 157 12706413
  126. [136]Toulmond S Rothwell NJ Interleukin-1 receptor antagonist inhibits neuronal damage caused by fluid percussion injury in the rat. Brain Res 1995 671 261 266 7743213
  127. [137]Tehranian R Andell-Jonsson S Beni SM Improved recovery and delayed cytokine induction after closed head injury in mice with central overexpression of the secreted isoform of the interleukin-1 receptor antagonist. J Neurotrauma 2002 19 939 951 12225654
  128. [138]Basu A Krady JK O'Malley M Styren SD DeKosky ST Levison SW The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury. J Neurosci 2002 22 6071 6082 12122068 PMC6757935
  129. [139]Ross SA Halliday MI Campbell GC Byrnes DP Rowlands BJ The presence of tumour necrosis factor in CSF and plasma after severe head injury. Br J Neurosurg 1994 8 419 425 7811406
  130. [140]Goodman JC Robertson CS Grossman RG Narayan RK Elevation of tumor necrosis factor in head injury. J Neuroimmunol 1990 30 213 217 2229409
  131. [141]Stover JF Schoning B Beyer TF Woiciechowsky C Unterberg AW Temporal profile of cerebrospinal fluid glutamate, interleukin-6, and tumor necrosis factor-alpha in relation to brain edema and contusion following controlled cortical impact injury in rats. Neurosci Lett 2000 288 25 28 10869807
  132. [142]Shohami E Novikov M Bass R Yamin A Gallily R Closed head injury triggers early production of TNF alpha and IL-6 by brain tissue. J Cereb Blood Flow Metab 1994 14 615 619 8014208
  133. [143]Fan L Young PR Barone FC Feuerstein GZ Smith DH McIntosh TK Experimental brain injury induces differential expression of tumor necrosis factor-alpha mRNA in the CNS. Brain Res Mol Brain Res 1996 36 287 291 8965649
  134. [144]Sullivan PG Bruce-Keller AJ Rabchevsky AG Exacerbation of damage and altered NF-kappaB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury. J Neurosci 1999 19 6248 6256 10414954 PMC6782813
  135. [145]Scherbel U Raghupathi R Nakamura M Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc Natl Acad Sci U S A 1999 96 8721 8726 10411942 PMC17583
  136. [146]Morganti-Kossmann MC Hans VH Lenzlinger PM TGF-beta is elevated in the CSF of patients with severe traumatic brain injuries and parallels blood-brain barrier function. J Neurotrauma 1999 16 617 628 10447073
  137. [147]Csuka E Morganti-Kossmann MC Lenzlinger PM Joller H Trentz O Kossmann T IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta1 and blood-brain barrier function. J Neuroimmunol 1999 101 211 221 10580806
  138. [148]Knoblach SM Faden AI Interleukin-10 improves outcome and alters proinflammatory cytokine expression after experimental traumatic brain injury. Exp Neurol 1998 153 143 151 9743576
  139. [149]Kremlev SG Palmer C Interleukin-10 inhibits endotoxin-induced pro-inflammatory cytokines in microglial cell cultures. J Neuroimmunol 2005 162 71 80 15833361
  140. [150]Tyor WR Avgeropoulos N Ohlandt G Hogan EL Treatment of spinal cord impact injury in the rat with transforming growth factor-beta. J Neurol Sci 2002 200 33 41 12127673
  141. [151]Hamada Y Ikata T Katoh S Effects of exogenous transforming growth factor-beta 1 on spinal cord injury in rats. Neurosci Lett 1996 203 97 100 8834102
  142. [152]Lucin KM Wyss-Coray T Immune activation in brain aging and neurodegeneration: too much or too little? Neuron 2009 64 110 122 19840553 PMC2834890
  143. [153]Galbraith S Head injuries in the elderly. Br Med J (Clin Res Ed) 1987 294 325 PMC1245343 3101859
  144. [154]Pennings JL Bachulis BL Simons CT Slazinski T Survival after severe brain injury in the aged. Arch Surg 1993 128 787 793 discussion 793-784 8317961
  145. [155]Sandhir R Onyszchuk G Berman NE Exacerbated glial response in the aged mouse hippocampus following controlled cortical impact injury. Exp Neurol 2008 213 372 380 18692046 PMC2662478
  146. [156]Conde JR Streit WJ Effect of aging on the microglial response to peripheral nerve injury. Neurobiol Aging 2006 27 1451 1461 16159684
  147. [157]Popa-Wagner A Carmichael ST Kokaia Z Kessler C Walker LC The response of the aged brain to stroke: too much, too soon? Curr Neurovasc Res 2007 4 216 227 17691975
  148. [158]Graves AB White E Koepsell TD The association between head trauma and Alzheimer's disease. Am J Epidemiol 1990 131 491 501 2405648
  149. [159]Mortimer JA French LR Hutton JT Schuman LM Head injury as a risk factor for Alzheimer's disease. Neurology 1985 35 264 267 3969219
  150. [160]van Duijn CM Tanja TA Haaxma R Head trauma and the risk of Alzheimer's disease. Am J Epidemiol 1992 135 775 782 1595677
  151. [162]Roberts GW Gentleman SM Lynch A Graham DI beta A4 amyloid protein deposition in brain after head trauma. Lancet 1991 338 1422 1423 1683421
  152. [165]Yankner BA Dawes LR Fisher S Villa-Komaroff L Oster-Granite ML Neve RL Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science 1989 245 417 420 2474201
  153. [166]Cagnin A Brooks DJ Kennedy AM In-vivo measurement of activated microglia in dementia. Lancet 2001 358 461 467 11513911
  154. [168]Ii M Sunamoto M Ohnishi K Ichimori Y beta-Amyloid protein-dependent nitric oxide production from microglial cells and neurotoxicity. Brain Res 1996 720 93 100 8782901
  155. [169]Holmin S Mathiesen T Long-term intracerebral inflammatory response after experimental focal brain injury in rat. Neuroreport 1999 10 1889 1891 10501527
  156. [170]Yrjanheikki J Keinanen R Pellikka M Hokfelt T Koistinaho J Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci U S A 1998 95 15769 15774 9861045 PMC28119
  157. [171]Tikka T Fiebich BL Goldsteins G Keinanen R Koistinaho J Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 2001 21 2580 2588 11306611 PMC6762519
  158. [172]Kremlev SG Roberts RL Palmer C Differential expression of chemokines and chemokine receptors during microglial activation and inhibition. J Neuroimmunol 2004 149 1 9 15020059
  159. [173]Choi SH Lee DY Chung ES Hong YB Kim SU Jin BK Inhibition of thrombin-induced microglial activation and NADPH oxidase by minocycline protects dopaminergic neurons in the substantia nigra in vivo. J Neurochem 2005 95 1755 1765 16219027
  160. [174]Seabrook TJ Jiang L Maier M Lemere CA Minocycline affects microglia activation, Abeta deposition, and behavior in APP-tg mice. Glia 2006 53 776 782 16534778
  161. [175]Sanchez Mejia RO Ona VO Li M Friedlander RM Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery 2001 48 1393 1399 discussion 1399-1401 11383749
  162. [176]Lee SM Yune TY Kim SJ Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma 2003 20 1017 1027 14588118
  163. [177]Wells JE Hurlbert RJ Fehlings MG Yong VW Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain 2003 126 1628 1637 12805103
  164. [178]Stirling DP Khodarahmi K Liu J Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. J Neurosci 2004 24 2182 2190 14999069 PMC6730425
  165. [179]Teng YD Choi H Onario RC Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury. Proc Natl Acad Sci U S A 2004 101 3071 3076 14981254 PMC365746
  166. [180]Yune TY Lee JY Jung GY Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. J Neurosci 2007 27 7751 7761 17634369 PMC6672884
  167. [181]Festoff BW Ameenuddin S Arnold PM Wong A Santacruz KS Citron BA Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury. J Neurochem 2006 97 1314 1326 16638021
  168. [182]Berger J Moller DE The mechanisms of action of PPARs. Annu Rev Med 2002 53 409 435 11818483
  169. [183]Chawla A Barak Y Nagy L Liao D Tontonoz P Evans RM PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med 2001 7 48 52 11135615
  170. [184]Pereira MP Hurtado O Cardenas A Rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 cause potent neuroprotection after experimental stroke through noncompletely overlapping mechanisms. J Cereb Blood Flow Metab 2006 26 218 229 16034372
  171. [185]Sundararajan S Gamboa JL Victor NA Wanderi EW Lust WD Landreth GE Peroxisome proliferator-activated receptor-gamma ligands reduce inflammation and infarction size in transient focal ischemia. Neuroscience 2005 130 685 696 15590152
  172. [186]Park SW Yi JH Miranpuri G Thiazolidinedione class of peroxisome proliferator-activated receptor gamma agonists prevents neuronal damage, motor dysfunction, myelin loss, neuropathic pain, and inflammation after spinal cord injury in adult rats. J Pharmacol Exp Ther 2007 320 1002 1012 17167171
  173. [187]Collino M Aragno M Mastrocola R Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Eur J Pharmacol 2006 530 70 80 16386242
  174. [188]Bernardo A Minghetti L PPAR-gamma agonists as regulators of microglial activation and brain inflammation. Curr Pharm Des 2006 12 93 109 16454728
  175. [189]Bethea JR Nagashima H Acosta MC Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma 1999 16 851 863 10547095
  176. [190]Morganti-Kossmann MC Rancan M Stahel PF Kossmann T Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr Opin Crit Care 2002 8 101 105 12386508
  177. [191]Lenzlinger PM Morganti-Kossmann MC Laurer HL McIntosh TK The duality of the inflammatory response to traumatic brain injury. Mol Neurobiol 2001 24 169 181 11831551
  178. [192]Tian DS Xie MJ Yu ZY Cell cycle inhibition attenuates microglia induced inflammatory response and alleviates neuronal cell death after spinal cord injury in rats. Brain Res 2007 1135 177 185 17188663
  179. [193]Dijkstra S Duis S Pans IM Intraspinal administration of an antibody against CD81 enhances functional recovery and tissue sparing after experimental spinal cord injury. Exp Neurol 2006 202 57 66 16806185
  180. [194]Gadient RA Cron KC Otten U Interleukin-1 beta and tumor necrosis factor-alpha synergistically stimulate nerve growth factor (NGF) release from cultured rat astrocytes. Neurosci Lett 1990 117 335 340 2094822
  181. [195]Bouhy D Malgrange B Multon S Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages. FASEB J 2006 16636109
  182. [196]Prewitt CM Niesman IR Kane CJ Houle JD Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp Neurol 1997 148 433 443 9417823
  183. [197]Stoica B Byrnes K Faden AI Multifunctional drug treatment in neurotrauma. Neurotherapeutics 2009 6 14 27 19110196 PMC2996269
  184. [198]Byrnes KR Loane DJ Faden AI Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders. Neurotherapeutics 2009 6 94 107 19110202 PMC2634659

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Authors
Loane, D. J., & Byrnes, K. R.
Affiliations
  • University of Maryland, Baltimore (US)
  • Uniformed Services University of the Health Sciences (US)
Corresponding author
Byrnes, Kimberly R.
ORCID
Venue
Neurotherapeutics
Publisher
Elsevier BV
Published
2010-10
Volume
7
Issue
4
Pages
366-377
ISSN
1878-7479 (ISSN-L)
DOI
10.1016/j.nurt.2010.07.002
PMC
PMC2948548
OpenAlex
W1984737307
Cited by
657
References
13
Citations by year
2026: 14 · 2025: 29 · 2024: 34 · 2023: 36 · 2022: 29 · 2021: 34 · 2020: 47 · 2019: 54 · 2018: 53 · 2017: 60 · 2016: 50 · 2015: 51 · 2014: 54 · 2013: 52 · 2012: 42
FWCI
2.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurotherapeutics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS054221)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
Keywords
microglia, neurotrauma, secondary injury, microglial activation, cytokines, chemokines, nitric oxide, prostaglandins, growth factors, spinal cord injury, traumatic brain injury, functional recovery
MeSH terms
Animals, Brain Injuries, Central Nervous System, Humans, Immunity, Innate, Inflammation, Models, Biological, Spinal Cord Injuries, Microglia

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