Critical role of microglia in the inflammatory response after spinal injury


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Ya-Yun Shi 1, Wan-Yun Liu; Fu-Chao Wang*
Author Affiliations
∗Correspondence author e-mail: WangF @nju.edu.cn: Nanjing University, 163 Xianlin Avenue, China

 

Abstract

The spinal cord, comprising nerve cells and supporting cells, is a vital component of the central nervous system (CNS) that connects the brain to the body. It is part of a bony structure, the vertebral column, which protects the delicate cord from external damage. Various factors can cause spinal cord injuries (SCIs) that disrupt its structure and function, leading to devastating consequences for affected individuals. It is important to understand SCIs, their causes, structure, consequences, and pathology to inform research and therapeutic efforts. As SCIs severely damage the CNS, which doesn’t regenerate after injury, efficient pathways to repair the nervous system must be found. This is understood as a cellular response to injury, currently focusing on immune and glial inflammation. Microglia are the resident immune cells of the brain, fulfilling roles in the maintenance, repair, and homeostasis of the healthy CNS, and responding to injury and disease. While they perform beneficial, protective roles under some circumstances, they can also harm cells by the release of neurotoxic molecules. This dual action makes them a prime candidate for possible therapeutic interventions in various neurological disorders, including SCIs. The proper functioning of the spinal cord and the integrity of the spinal cord pathway mechanisms are essential for an unaffected or intact interchange between the body and the brain. However, a spinal injury or the rupture of the spinal cord-producing lesion interrupts these pathways. The kinds of lesions can happen through disease, trauma, congenital malformation, or injection of a drug. The types or classes of injury producing insults can be classified into two categories: complete and incomplete. In a complete injury, the spinal cord is completely damaged, and there is a complete loss of function below the level of injury. In an incomplete injury, the spinal cord is partially damaged, function below the level of injury is not completely lost, and the deficit varies in the extent of damage to different tracts.

Keywords: Spinal cord injury; Microglia; Pro-inflammatory cytokines; CNS; Immune cells

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.

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References

  1. Weinstein JR, Koerner IP, Moller T. Microglia in ischemic brain injury. Future Neurol 2010;5:227-246.
    https://doi.org/10.2217/fnl.10.1
  2. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 1999;22(9):391-397.
    https://doi.org/10.1016/S0166-2236(99)01401-0
  3. Tanaka M, Sotomatsu A, Yoshida T, Hirai S, Nishida A. Detection of superoxide production by activated microglia using a sensitive and specific chemiluminescence assay and microglia-mediated PC12h cell death. J Neurochem 1994; 63(1): 266-270.
    https://doi.org/10.1046/j.1471-4159.1994.63010266.x
  4. Vilhardt F. Microglia: phagocyte and glia cell. Int J Biochem Cell Biol 2005;37:17-21.
    https://doi.org/10.1016/j.biocel.2004.06.010
  5. Liu GJ, Nagarajah R, Banati RB, Bennett MR. Glutamate induces directed chemotaxis of microglia. Eur J Neurosci 2009;29:1108-1118.
    https://doi.org/10.1111/j.1460-9568.2009.06659.x
  6. Shaked I, Tchoresh D, Gersner R, et al. Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J Neurochem 2005;92:997-1009.
    https://doi.org/10.1111/j.1471-4159.2004.02954.x
  7. Albright AV, Gonzalez-Scarano F. Microarray analysis of activated mixed glial (microglia) and monocyte-derived macrophage gene expression. J Neuroimmunol 2004;157:27-38.
    https://doi.org/10.1016/j.jneuroim.2004.09.007
  8. Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 2005;76:77-98.
    https://doi.org/10.1016/j.pneurobio.2005.06.004
  9. Pei Z, Pang H, Qian L, et al. MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Glia 2007;55:1362-1373.
    https://doi.org/10.1002/glia.20545
  10. 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.
    https://doi.org/10.1186/1742-2094-5-43
  11. Ramote D, Kishony J, Bren L. Role of monocyte chemoattractant protein-1 (MCP-1) in atherosclerosis: Signature of monocytes and macrophages. American Journal of BioMedicine 2014;2(1):67-79.
    https://doi.org/10.18081/2333-5106/014-01/67-79
  12. 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.
    https://doi.org/10.1523/JNEUROSCI.23-15-06181.2003
  13. Lai AY, Todd KG. Microglia in cerebral ischemia: molecular actions and interactions. Can. J. Physiol. Pharmacol 2006;84(1):49-59.
    https://doi.org/10.1139/Y05-143
  14. Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005;308(5726):1314-1318.
    https://doi.org/10.1126/science.1110647
  15. Colton CA. Heterogeneity of microglial activation in the innate immune response in the brain. J. Neuroimmune Pharmacol 2009;4(4):399-418.
    https://doi.org/10.1007/s11481-009-9164-4
  16. Yenari MA, Giffard RG. Ischemic vulnerability of primary murine microglial cultures. Neurosci. Lett 2001;298(1):5-8.
    https://doi.org/10.1016/S0304-3940(00)01724-9
  17. Weinstein JR, Zhang M, Kutlubaev M, et al. Thrombin-induced regulation of cd95(FAS) expression in the n9 microglial cell line: evidence for involvement of proteinase-activated receptor(1) and extracellular signal-regulated kinase 1/2. Neurochem. Res 2009;34(3):445-452.
    https://doi.org/10.1007/s11064-008-9803-9
  18. 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. USA 1998;95(26):15769-15774.
    https://doi.org/10.1073/pnas.95.26.15769
  19. Hooper C, Taylor DL, Pocock JM. Pure albumin is a potent trigger of calcium signalling and proliferation in microglia but not macrophages or astrocytes. J. Neurochem 2005;92(6):1363-1376.
    https://doi.org/10.1111/j.1471-4159.2005.02982.x
  20. Cardona AE, Pioro EP, Sasse ME, et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat. Neurosci 2006;9(7):917-924.
    https://doi.org/10.1038/nn1715
  21. Godbout JP, Chen J, Abraham J, et al. Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J 2005;19:1329-1331.
    https://doi.org/10.1096/fj.05-3776fje
  22. Conde JR, Streit WJ. Microglia in the aging brain. J Neuropathol Exp Neurol 2006;65:199-203.
    https://doi.org/10.1097/01.jnen.0000202887.22082.63
  23. Takahashi K, Rochford CD, Neumann H. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med 2005;201:647-657.
    https://doi.org/10.1084/jem.20041611
  24. Colton CA. Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 2009;4:399-418.
    https://doi.org/10.1007/s11481-009-9164-4
  25. 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.
  26. 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.
    https://doi.org/10.1002/(SICI)1521-4141(199904)29:04<1275::AID-IMMU1275>3.0.CO;2-T
  27. 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.
    https://doi.org/10.1074/jbc.M702899200
  28. Bareyre FM, Schwab ME. Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci 2003;26:555-563.
    https://doi.org/10.1016/j.tins.2003.08.004
  29. Benveniste EN. Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am J Physiol 1992;263:C1-16.
    https://doi.org/10.1152/ajpcell.1992.263.1.C1
  30. 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.
    https://doi.org/10.1002/ana.10472
  31. Tian DS, Xie MJ, Yu ZY, et al. 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.
    https://doi.org/10.1016/j.brainres.2006.11.085

Research Article


DOI: http://dx.doi.org/10.18081/2333-5106/015-03/453-462
American Journal of BioMedicine 2015, Volume 3, Issue 3, pages 123-140
Received 11 March 2015; accepted June; 09, 2015, Published July 11, 2015

How to cite this article
Shi Y, Liu WY, Wang FC. Critical role of microglia in the inflammatory response after spinal injury. American Journal of BioMedicine 2015;3(3):123–140
Review Article
1. Abstract
2. Keywords
3. Introduction
5. Results
6. Discussion
7. References

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