Skip to main content
Top
Published in: Translational Stroke Research 6/2015

01-12-2015 | Commentary

Microglia/Macrophage Polarization After Experimental Intracerebral Hemorrhage

Published in: Translational Stroke Research | Issue 6/2015

Login to get access

Excerpt

Microglia are the resident macrophages of the brain and are the first responders to immune system activation in that tissue. Under resting conditions, microglia are ramified and monitor the brain microenvironment maintaining neuron, astrocyte, and oligodendrocyte coordination. In conditions such as intracerebral hemorrhage (ICH), traumatic brain injury (TBI), subarachnoid hemorrhage, and cerebral ischemia, microglia become activated as part of the injury response [17]. Upon activation, microglia transform into an amoeboid phenotype and consequently play roles in inflammatory reactions and phagocytosis of necrotic tissue. However, based on protein and mRNA expression, activated microglia have different phenotypes. Classically, these have been termed M1- and M2-polarized microglia/macrophages and they have different roles in brain injury [4]. Until now, most studies on microglial polarization have focused on TBI and cerebral ischemia, and relatively little is known about the polarization of microglia/macrophages following ICH. In this commentary, we will discuss some known molecular mechanisms that mediate microglial phenotype transformation, discuss new therapeutic approaches to altering the balance of microglial activation phenotypes, and identify future directions that could aid in long-term recovery after ICH. …
Literature
2.
go back to reference Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63.CrossRefPubMed Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63.CrossRefPubMed
3.
go back to reference Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720–31.CrossRefPubMed Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720–31.CrossRefPubMed
4.
go back to reference Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, et al. Microglial and macrophage polarization—new prospects for brain repair. Nat Rev Neurol. 2015;11(1):56–64.CrossRefPubMed Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, et al. Microglial and macrophage polarization—new prospects for brain repair. Nat Rev Neurol. 2015;11(1):56–64.CrossRefPubMed
5.
go back to reference Aungst SL, Kabadi SV, Thompson SM, Stoica BA, Faden AI. Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits. J Cereb Blood Flow Metab. 2014;34(7):1223–32.PubMedCentralCrossRefPubMed Aungst SL, Kabadi SV, Thompson SM, Stoica BA, Faden AI. Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits. J Cereb Blood Flow Metab. 2014;34(7):1223–32.PubMedCentralCrossRefPubMed
6.
go back to reference Xi G, Strahle J, Hua Y, Keep RF. Progress in translational research on intracerebral hemorrhage: is there an end in sight? Prog Neurobiol. 2014;115:45–63.CrossRefPubMed Xi G, Strahle J, Hua Y, Keep RF. Progress in translational research on intracerebral hemorrhage: is there an end in sight? Prog Neurobiol. 2014;115:45–63.CrossRefPubMed
7.
go back to reference Pennypacker KR. Targeting the peripheral inflammatory response to stroke: role of the spleen. Transl Stroke Res. 2014;5(6):635–7.CrossRefPubMed Pennypacker KR. Targeting the peripheral inflammatory response to stroke: role of the spleen. Transl Stroke Res. 2014;5(6):635–7.CrossRefPubMed
8.
go back to reference Boche D, Perry VH, Nicoll JA. Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol. 2013;39(1):3–18.CrossRefPubMed Boche D, Perry VH, Nicoll JA. Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol. 2013;39(1):3–18.CrossRefPubMed
9.
go back to reference Boscia F, D’Avanzo C, Pannaccione A, Secondo A, Casamassa A, Formisano L, et al. New roles of NCX in glial cells: activation of microglia in ischemia and differentiation of oligodendrocytes. Adv Exp Med Biol. 2013;961:307–16.CrossRefPubMed Boscia F, D’Avanzo C, Pannaccione A, Secondo A, Casamassa A, Formisano L, et al. New roles of NCX in glial cells: activation of microglia in ischemia and differentiation of oligodendrocytes. Adv Exp Med Biol. 2013;961:307–16.CrossRefPubMed
10.
go back to reference Fetler L, Amigorena S. Neuroscience. Brain under surveillance: the microglia patrol. Science. 2005 Jul 15;309(5733):392-3. Fetler L, Amigorena S. Neuroscience. Brain under surveillance: the microglia patrol. Science. 2005 Jul 15;309(5733):392-3.
11.
go back to reference Kettenmann H, Kirchhoff F, Verkhratsky A. Microglia: new roles for the synaptic stripper. Neuron. 2013 Jan 9;77 (1):10-8. Kettenmann H, Kirchhoff F, Verkhratsky A. Microglia: new roles for the synaptic stripper. Neuron. 2013 Jan 9;77 (1):10-8.
12.
go back to reference Salter MW, Beggs S. Sublime microglia: expanding roles for the guardians of the CNS. Cell. 2014 Jul 3;158 (1):15-24. Salter MW, Beggs S. Sublime microglia: expanding roles for the guardians of the CNS. Cell. 2014 Jul 3;158 (1):15-24.
13.
go back to reference Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. The role of microglia in the healthy brain. J Neurosci. 2011 Nov 9;31 (45):16064-9. Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. The role of microglia in the healthy brain. J Neurosci. 2011 Nov 9;31 (45):16064-9.
15.
go back to reference Girard S, Brough D, Lopez-Castejon G, Giles J, Rothwell NJ, Allan SM. Microglia and macrophages differentially modulate cell death after brain injury caused by oxygen-glucose deprivation in organotypic brain slices. Glia. 2013;61(5):813–24.PubMedCentralCrossRefPubMed Girard S, Brough D, Lopez-Castejon G, Giles J, Rothwell NJ, Allan SM. Microglia and macrophages differentially modulate cell death after brain injury caused by oxygen-glucose deprivation in organotypic brain slices. Glia. 2013;61(5):813–24.PubMedCentralCrossRefPubMed
16.
go back to reference Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91(2):461–553.CrossRefPubMed Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91(2):461–553.CrossRefPubMed
18.
go back to reference Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol. 2014;115:25–44.CrossRefPubMed Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol. 2014;115:25–44.CrossRefPubMed
20.
go back to reference Hu X, Li P, Guo Y, Wang H, Leak RK, Chen S, et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke. 2012;43(11):3063–70.CrossRefPubMed Hu X, Li P, Guo Y, Wang H, Leak RK, Chen S, et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke. 2012;43(11):3063–70.CrossRefPubMed
21.
go back to reference Jin H, Xi G, Keep RF, Wu J, Hua Y. DARPP-32 to quantify intracerebral hemorrhage-induced neuronal death in basal ganglia. Transl Stroke Res. 2013;4(1):130–4.PubMedCentralCrossRefPubMed Jin H, Xi G, Keep RF, Wu J, Hua Y. DARPP-32 to quantify intracerebral hemorrhage-induced neuronal death in basal ganglia. Transl Stroke Res. 2013;4(1):130–4.PubMedCentralCrossRefPubMed
22.
go back to reference Wang G, Zhang J, Hu X, Zhang L, Mao L, Jiang X, et al. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J Cereb Blood Flow Metab. 2013;33(12):1864–74.PubMedCentralCrossRefPubMed Wang G, Zhang J, Hu X, Zhang L, Mao L, Jiang X, et al. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J Cereb Blood Flow Metab. 2013;33(12):1864–74.PubMedCentralCrossRefPubMed
23.
go back to reference Gao HM, Liu B, Hong JS. Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci. 2003 Jul 16;23 (15):6181-7. Gao HM, Liu B, Hong JS. Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci. 2003 Jul 16;23 (15):6181-7.
24.
go back to reference Qin L, Liu Y, Wang T, Wei SJ, Block ML, Wilson B, et al. NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem. 2004 Jan 9;279 (2):1415-21. Qin L, Liu Y, Wang T, Wei SJ, Block ML, Wilson B, et al. NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem. 2004 Jan 9;279 (2):1415-21.
25.
go back to reference Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, et al. Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol. 2007;61(4):352–62.CrossRefPubMed Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, et al. Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol. 2007;61(4):352–62.CrossRefPubMed
26.
go back to reference Benton RL, Hagg T. Vascular pathology as a potential therapeutic target in SCI. Transl Stroke Res. 2011;2(4):556–74.CrossRefPubMed Benton RL, Hagg T. Vascular pathology as a potential therapeutic target in SCI. Transl Stroke Res. 2011;2(4):556–74.CrossRefPubMed
27.
go back to reference Zhao J, Chen Z, Xi G, Keep RF, Hua Y. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats. Transl Stroke Res. 2014;5(5):586–94.PubMedCentralCrossRefPubMed Zhao J, Chen Z, Xi G, Keep RF, Hua Y. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats. Transl Stroke Res. 2014;5(5):586–94.PubMedCentralCrossRefPubMed
28.
go back to reference Lee DC, Ruiz CR, Lebson L, Selenica ML, Rizer J, Hunt Jr JB, et al. Aging enhances classical activation but mitigates alternative activation in the central nervous system. Neurobiol Aging. 2013;34(6):1610–20.PubMedCentralCrossRefPubMed Lee DC, Ruiz CR, Lebson L, Selenica ML, Rizer J, Hunt Jr JB, et al. Aging enhances classical activation but mitigates alternative activation in the central nervous system. Neurobiol Aging. 2013;34(6):1610–20.PubMedCentralCrossRefPubMed
29.
go back to reference Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC, Means TK, et al. The microglial sensome revealed by direct RNA sequencing. Nat Neurosci. 2013;16(12):1896–905.CrossRefPubMed Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC, Means TK, et al. The microglial sensome revealed by direct RNA sequencing. Nat Neurosci. 2013;16(12):1896–905.CrossRefPubMed
30.
go back to reference Kroner A, Greenhalgh AD, Zarruk JG, Passos Dos Santos R, Gaestel M, David S. TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron. 2014 Sep 3;83 (5):1098-116. Kroner A, Greenhalgh AD, Zarruk JG, Passos Dos Santos R, Gaestel M, David S. TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron. 2014 Sep 3;83 (5):1098-116.
31.
go back to reference Chawla A. Control of macrophage activation and function by PPARs. Circ Res. 2010 May 28;106 (10):1559-69. PubMed Pubmed Central PMCID: 2897247. Chawla A. Control of macrophage activation and function by PPARs. Circ Res. 2010 May 28;106 (10):1559-69. PubMed Pubmed Central PMCID: 2897247.
32.
go back to reference Loane DJ, Stoica BA, Byrnes KR, Jeong W, Faden AI. Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury. J Neurotrauma. 2013 Mar 1;30 (5):403-12. PubMed Pubmed Central PMCID: 3589874. Loane DJ, Stoica BA, Byrnes KR, Jeong W, Faden AI. Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury. J Neurotrauma. 2013 Mar 1;30 (5):403-12. PubMed Pubmed Central PMCID: 3589874.
33.
go back to reference Zanier ER, Pischiutta F, Riganti L, Marchesi F, Turola E, Fumagalli S, et al. Bone marrow mesenchymal stromal cells drive protective M2 microglia polarization after brain trauma. Neurotherapeutics. 2014;11(3):679–95.PubMedCentralCrossRefPubMed Zanier ER, Pischiutta F, Riganti L, Marchesi F, Turola E, Fumagalli S, et al. Bone marrow mesenchymal stromal cells drive protective M2 microglia polarization after brain trauma. Neurotherapeutics. 2014;11(3):679–95.PubMedCentralCrossRefPubMed
34.
go back to reference Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, et al. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of l-arginine metabolism. J Immunol. 2001 Dec 1;167 (11):6533-44. Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, et al. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of l-arginine metabolism. J Immunol. 2001 Dec 1;167 (11):6533-44.
Metadata
Title
Microglia/Macrophage Polarization After Experimental Intracerebral Hemorrhage
Publication date
01-12-2015
Published in
Translational Stroke Research / Issue 6/2015
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-015-0428-4

Other articles of this Issue 6/2015

Translational Stroke Research 6/2015 Go to the issue