Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 38, 2016, Pages E5665-E5674

  Varvel, Nicholas H ^a   Neher, Jonas J ^b,c   Bosch, Andrea ^b,c   Wang, Wenyi ^a   Ransohoff, Richard M ^d   Miller, Richard J ^e   Dingledine, Raymond ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF TÜBINGEN   (Germany)

^c GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^d BIOGEN   (United States)

^e NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Epileptogenesis; Microgliosis; Myeloid cell heterogeneity; Neuroprotection; Seizure

Indexed keywords

CHEMOKINE RECEPTOR CCR2; INTERLEUKIN 1BETA; MONOCYTE CHEMOTACTIC PROTEIN 1; CCL2 PROTEIN, MOUSE; CCR2 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; CD3+ T LYMPHOCYTE; CELL INFILTRATION; CELL INVASION; CELL ISOLATION; CONTROLLED STUDY; ENCEPHALITIS; EPILEPTIC STATE; FEMALE; HIPPOCAMPUS; INNATE IMMUNITY; MACROPHAGE; MALE; MICROGLIA; MONOCYTE; MOUSE; NERVE CELL LESION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; ANIMAL; GENETICS; GLIOSIS; IMMUNOLOGY; KNOCKOUT MOUSE; METABOLISM; NERVE CELL; PATHOLOGY; SEIZURE;

ANIMALS; BLOOD-BRAIN BARRIER; CHEMOKINE CCL2; ENCEPHALITIS; GLIOSIS; IMMUNITY, INNATE; INTERLEUKIN-1BETA; MICE; MICE, KNOCKOUT; MONOCYTES; NEURONS; RECEPTORS, CCR2; SEIZURES; STATUS EPILEPTICUS;

EID: 84988706183     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1604263113     Document Type: Article

References (70)

1. Varvel NH, Jiang J, Dingledine R (2015) Candidate drug targets for prevention or modification of epilepsy. Annu Rev Pharmacol Toxicol 55:229-247.
2. van Vliet EA, et al. (2007) Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 130(pt 2):521-534.
3. Sakuma S, Halliday WC, Nomura R, Ochi A, Otsubo H (2014) Increased population of oligodendroglia-like cells in pediatric intractable epilepsy. Neurosci Lett 566:188-193.
4. Juhász C, et al. (2013) Successful surgical treatment of an inflammatory lesion associated with new-onset refractory status epilepticus. Neurosurg Focus 34(6):E5.
5. Vezzani A, Dingledine R, Rossetti AO (2015) Immunity and inflammation in status epilepticus and its sequelae: Possibilities for therapeutic application. Expert Rev Neurother 15(9):1081-1092.
6. Jiang J, et al. (2013) Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation. Proc Natl Acad Sci USA 110(9):3591-3596.
7. Maroso M, et al. (2011) Interleukin-1β biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice. Neurotherapeutics 8(2):304-315.
8. Rojas A, Ganesh T, Lelutiu N, Gueorguieva P, Dingledine R (2015) Inhibition of the prostaglandin EP2 receptor is neuroprotective and accelerates functional recovery in a rat model of organophosphorus induced status epilepticus. Neuropharmacology 93:15-27.
9. Serrano GE, et al. (2011) Ablation of cyclooxygenase-2 in forebrain neurons is neuroprotective and dampens brain inflammation after status epilepticus. J Neurosci 31(42):14850-14860.
10. Levin JR, Serrano G, Dingledine R (2012) Reduction in delayed mortality and subtle improvement in retrograde memory performance in pilocarpine-treated mice with conditional neuronal deletion of cyclooxygenase-2 gene. Epilepsia 53(8):1411-1420.
11. Prinz M, Priller J, Sisodia SS, Ransohoff RM (2011) Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci 14(10):1227-1235.
12. Mildner A, et al. (2009) CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain 132(pt 9):2487-2500.
13. Gyoneva S, et al. (2015) Ccr2 deletion dissociates cavity size and tau pathology after mild traumatic brain injury. J Neuroinflammation 12(1):228.
14. Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ (2000) CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 192(6):899-905.
15. Izikson L, Klein RS, Charo IF, Weiner HL, Luster AD (2000) Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J Exp Med 192(7):1075-1080.
16. Yamasaki R, et al. (2014) Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med 211(8):1533-1549.
17. London A, et al. (2011) Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J Exp Med 208(1):23-39.
18. Shechter R, et al. (2009) Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med 6(7):e1000113.
19. Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468(7321):253-262.
20. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314-1318.
21. Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10(12):1538-1543.
22. Mildner A, et al. (2007) Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat Neurosci 10(12):1544-1553.
23. Mizutani M, et al. (2012) The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. J Immunol 188(1):29-36.
24. Saederup N, et al. (2010) Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLoS One 5(10):e13693.
25. Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1):71-82.
26. Hsieh CL, et al. (2014) CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury. J Neurotrauma 31(20):1677-1688.
27. Mildner A, et al. (2011) Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer's disease. J Neurosci 31(31):11159-11171.
28. El Khoury J, et al. (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13(4):432-438.
29. Buckmaster PS, Dudek FE (1997) Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. J Comp Neurol 385(3):385-404.
30. Rojas A, et al. (2014) The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus. Neurobiol Dis 70:74-89.
31. Jung H, et al. (2009) Visualization of chemokine receptor activation in transgenic mice reveals peripheral activation of CCR2 receptors in states of neuropathic pain. J Neurosci 29(25):8051-8062.
32. Bell RD, et al. (2010) Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68(3):409-427.
33. Hawkes CA, McLaurin J (2009) Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. Proc Natl Acad Sci USA 106(4):1261-1266.
34. Galea I, et al. (2005) Mannose receptor expression specifically reveals perivascular macrophages in normal, injured, and diseased mouse brain. Glia 49(3):375-384.
35. Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FM (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 14(9):1142-1149.
36. Chu HX, et al. (2014) Role of CCR2 in inflammatory conditions of the central nervous system. J Cereb Blood Flow Metab 34(9):1425-1429.
37. Butovsky O, et al. (2012) Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest 122(9):3063-3087.
38. Butovsky O, et al. (2014) Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 17(1):131-143.
39. Jiang J, et al. (2015) Therapeutic window for cyclooxygenase-2 related anti-inflammatory therapy after status epilepticus. Neurobiol Dis 76:126-136.
40. Marchi N, et al. (2007) Seizure-promoting effect of blood-brain barrier disruption. Epilepsia 48(4):732-742.
41. Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57(2):178-201.
42. Buckmaster PS, Jongen-Reˆlo AL (1999) Highly specific neuron loss preserves lateral inhibitory circuits in the dentate gyrus of kainate-induced epileptic rats. J Neurosci 19(21):9519-9529.
43. Hochreiter-Hufford AE, et al. (2013) Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature 497(7448):263-267.
44. Lebson L, et al. (2010) Trafficking CD11b-positive blood cells deliver therapeutic genes to the brain of amyloid-depositing transgenic mice. J Neurosci 30(29):9651-9658.
45. Morganti JM, et al. (2015) CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive dysfunction induced by traumatic brain injury. J Neurosci 35(2):748-760.
46. Borges K, McDermott DL, Dingledine R (2004) Reciprocal changes of CD44 and GAP-43 expression in the dentate gyrus inner molecular layer after status epilepticus in mice. Exp Neurol 188(1):1-10.
47. Zattoni M, et al. (2011) Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy. J Neurosci 31(11):4037-4050.
48. van Vliet EA, Otte WM, Gorter JA, Dijkhuizen RM, Wadman WJ (2014) Longitudinal assessment of blood-brain barrier leakage during epileptogenesis in rats. A quantitative MRI study. Neurobiol Dis 63:74-84.
49. Umekawa T, Osman AM, Han W, Ikeda T, Blomgren K (2015) Resident microglia, rather than blood-derived macrophages, contribute to the earlier and more pronounced inflammatory reaction in the immature compared with the adult hippocampus after hypoxia-ischemia. Glia 63(12):2220-2230.
50. Sica A, et al. (1997) Bacterial lipopolysaccharide rapidly inhibits expression of C-C chemokine receptors in human monocytes. J Exp Med 185(5):969-974.
51. Varvel NH, et al. (2012) Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. Proc Natl Acad Sci USA 109(44):18150-18155.
52. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354(6):610-621.
53. Foresti ML, et al. (2009) Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following pilocarpine-induced status epilepticus. J Neuroinflammation 6:40.
54. Manley NC, Bertrand AA, Kinney KS, Hing TC, Sapolsky RM (2007) Characterization of monocyte chemoattractant protein-1 expression following a kainate model of status epilepticus. Brain Res 1182:138-143.
55. Turrin NP, Rivest S (2004) Innate immune reaction in response to seizures: Implications for the neuropathology associated with epilepsy. Neurobiol Dis 16(2):321-334.
56. Glabinski AR, et al. (1996) Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. J Immunol 156(11):4363-4368.
57. Quan Y, Jiang J, Dingledine R (2013) EP2 receptor signaling pathways regulate classical activation of microglia. J Biol Chem 288(13):9293-9302.
58. Shieh CH, Heinrich A, Serchov T, van Calker D, Biber K (2014) P2X7-dependent, but differentially regulated release of IL-6, CCL2, and TNF-α in cultured mouse microglia. Glia 62(4):592-607.
59. Dubé C, Vezzani A, Behrens M, Bartfai T, Baram TZ (2005) Interleukin-1beta contributes to the generation of experimental febrile seizures. Ann Neurol 57(1):152-155.
60. Araki T, Simon RP, Taki W, Lan JQ, Henshall DC (2002) Characterization of neuronal death induced by focally evoked limbic seizures in the C57BL/6 mouse. J Neurosci Res 69(5):614-621.
61. Dingledine R, Varvel NH, Dudek FE (2014) When and how do seizures kill neurons, and is cell death relevant to epileptogenesis? Adv Exp Med Biol 813:109-122.
62. Rothwell N (2003) Interleukin-1 and neuronal injury: Mechanisms, modification, and therapeutic potential. Brain Behav Immun 17(3):152-157.
63. Vainchtein ID, et al. (2014) In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed. Glia 62(10):1724-1735.
64. Vinet J, et al. (2016) Microglia are less pro-inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus. Glia 64(8):1350-1362.
65. Ivens S, et al. (2007) TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain 130(pt 2):535-547.
66. Biber K, Möller T, Boddeke E, Prinz M (2016) Central nervous system myeloid cells as drug targets: Current status and translational challenges. Nat Rev Drug Discov 15(2):110-124.
67. Borges K, et al. (2003) Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model. Exp Neurol 182(1):21-34.
68. Long JM, et al. (1998) Stereological analysis of astrocyte and microglia in aging mouse hippocampus. Neurobiol Aging 19(5):497-503.
69. Cardona AE, Huang D, Sasse ME, Ransohoff RM (2006) Isolation of murine microglial cells for RNA analysis or flow cytometry. Nat Protoc 1(4):1947-1951.
70. Cardona AE, et al. (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9(7):917-924.