Neurogenesis and inflammation after ischemic stroke: What is known and where we go from here

Journal of Cerebral Blood Flow and Metabolism

Volumn 34, Issue 10, 2014, Pages 1573-1584

  Tobin, Matthew K ^a   Bonds, Jacqueline A ^a   Minshall, Richard D ^a   Pelligrino, Dale A ^a   Testai, Fernando D ^a   Lazarov, Orly ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

acute stroke; brain ischemia; inflammation; neural stem cells; regeneration and recovery

Indexed keywords

ANTIINFLAMMATORY AGENT;

ADULT; BLOOD CLOT LYSIS; BRAIN INJURY; BRAIN ISCHEMIA; CELL DIFFERENTIATION; HUMAN; HUMORAL IMMUNITY; IMMUNOMODULATION; NERVOUS SYSTEM DEVELOPMENT; NERVOUS SYSTEM INFLAMMATION; NEURAL STEM CELL TRANSPLANTATION; NEUROPROTECTION; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PATHOPHYSIOLOGY; PHAGOCYTOSIS; PRIORITY JOURNAL; REGENERATIVE MEDICINE; REPERFUSION INJURY; REVIEW; ANIMAL; BRAIN; COMPLICATION; DRUG EFFECTS; IMMUNOLOGY; INFLAMMATION; NEURAL STEM CELL; TRANSPLANTATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; BRAIN; BRAIN ISCHEMIA; HUMANS; INFLAMMATION; NEURAL STEM CELLS; NEUROGENESIS;

EID: 84921718867     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2014.130     Document Type: Review

References (150)

1. Towfighi A, Saver JL. Stroke declines from third to fourth leading cause of death in the United States: historical perspective and challenges ahead. Stroke 2011; 42: 2351-2355.
2. Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet 2008; 371: 1612-1623.
3. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ et al. Heart disease and stroke statistics-2014 update: a report from the American Heart Association. Circulation 2014; 129: e28-e292.
4. Lakhan SE, Kirchgessner A, Hofer M. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 2009; 7: 97.
5. Schwamm LH, Ali SF, Reeves MJ, Smith EE, Saver JL, Messe S et al. Temporal trends in patient characteristics and treatment with intravenous thrombolysis among acute ischemic stroke patients at Get With The Guidelines-Stroke hospitals. Circ Cardiovasc Qual Outcomes 2013; 6: 543-549.
6. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van Praag H. When neurogenesis encounters aging and disease. Trends Neurosci 2010; 33: 569-579.
7. Borgens RB, Liu-Snyder P. Understanding secondary injury. Q Rev Biol 2012; 87: 89-127.
8. Zhang Q, Gao T, Luo Y, Chen X, Gao G, Gao X et al. Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease. PloS One 2012; 7: e33722.
9. Cao Z, Balasubramanian A, Marrelli SP. Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90minutes after reperfusion. Am J Physiol Regul Integr Comp Physiol 2014; 306: R149-R156.
10. Watcharotayangul J, Mao L, Xu H, Vetri F, Baughman VL, Paisansathan C et al. Post-ischemic vascular adhesion protein-1 inhibition provides neuroprotection in a rat temporary middle cerebral artery occlusion model. J Neurochem 2012; 123(Suppl 2): 116-124.
11. Thored P, Heldmann U, Gomes-Leal W, Gisler R, Darsalia V, Taneera J et al. Longterm accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia 2009; 57: 835-849.
12. Aktas O, Ullrich O, Infante-Duarte C, Nitsch R, Zipp F. Neuronal damage in brain inflammation. Arch Neurol 2007; 64: 185-189.
13. Minghetti L. Role of inflammation in neurodegenerative diseases. Curr Opin Neurol 2005; 18: 315-321.
14. Eikelenboom P, Veerhuis R, Scheper W, Rozemuller AJ, van Gool WA, Hoozemans JJ. The significance of neuroinflammation in understanding Alzheimer's disease. J Neural Transm 2006; 113: 1685-1695.
15. del Zoppo GJ. Acute anti-inflammatory approaches to ischemic stroke. Ann N Y Acad Sci 2010; 1207: 143-148.
16. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leuk Biol 2010; 87: 779-789.
17. Amantea D, Nappi G, Bernardi G, Bagetta G, Corasaniti MT. Post-ischemic brain damage: pathophysiology and role of inflammatory mediators. FEBS J 2009; 276: 13-26.
18. Kriz J. Inflammation in ischemic brain injury: timing is important. Crit Rev Neurobiol 2006; 18: 145-157.
19. Schilling M, Besselmann M, Leonhard C, Mueller M, Ringelstein EB, Kiefer R. Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia: a study in green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol 2003; 183: 25-33.
20. Tanaka R, Komine-Kobayashi M, Mochizuki H, Yamada M, Furuya T, Migita M et al. Migration of enhanced green fluorescent protein expressing bone marrowderived microglia/macrophage into the mouse brain following permanent focal ischemia. Neuroscience 2003; 117: 531-539.
21. Janardhan V, Qureshi AI. Mechanisms of ischemic brain injury. Curr Cardiol Rep 2004; 6: 117-123.
22. Fiscus RR, Yuen JP, Chan SL, Kwong JH, Chew SB. Nitric oxide and cyclic GMP as pro-and anti-apoptotic agents. J Cardiac Surg 2002; 17: 336-339.
23. Rezai-Zadeh K, Gate D, Town T. CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease? J Neuroimmune Pharmacol 2009; 4: 462-475.
24. Stevens SL, Bao J, Hollis J, Lessov NS, Clark WM, Stenzel-Poore MP. The use of flow cytometry to evaluate temporal changes in inflammatory cells following focal cerebral ischemia in mice. Brain Res 2002; 932: 110-119.
25. Konsman JP, Drukarch B, Van Dam AM. (Peri)vascular production and action of pro-inflammatory cytokines in brain pathology. Clin Sci 2007; 112: 1-25.
26. Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med 2011; 17: 796-808.
27. Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity 2005; 23: 344-346.
28. Yilmaz G, Granger DN. Leukocyte recruitment and ischemic brain injury. Neuromol Med 2010; 12: 193-204.
29. Stenzel W, Alber G. Regulation of the inflammatory response in brain. In: Lajtha A, Galoyan A, Besedovsky HO (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer: US, 2008, pp 235-262.
30. Hickey WF, Hsu BL, Kimura H. T-lymphocyte entry into the central nervous system. J Neurosci Res 1991; 28: 254-260.
31. Kunis G, Baruch K, Rosenzweig N, Kertser A, Miller O, Berkutzki T et al. IFNgamma-dependent activation of the brain's choroid plexus for CNS immune surveillance and repair. Brain 2013; 136(Pt 11): 3427-3440.
32. Schwartz M, Kipnis J, Rivest S, Prat A. How do immune cells support and shape the brain in health, disease, and aging? J Neurosci 2013; 33: 17587-17596.
33. Aguzzi A, Barres BA, Bennett ML. Microglia: scapegoat, saboteur, or something else? Science 2013; 339: 156-161.
34. Spite M, Serhan CN. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circ Res 2010; 107: 1170-1184.
35. Schilling M, Besselmann M, Muller M, Strecker JK, Ringelstein EB, Kiefer R. Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia: an investigation using green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol 2005; 196: 290-297.
36. Denes A, Vidyasagar R, Feng J, Narvainen J, McColl BW, Kauppinen RA et al. Proliferating resident microglia after focal cerebral ischaemia in mice. J Cereb Blood Flow Metab 2007; 27: 1941-1953.
37. Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 2000; 425: 479-494.
38. Ming GL, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 2011; 70: 687-702.
39. Suh H, Deng W, Gage FH. Signaling in adult neurogenesis. Annu Rev Cell Dev Biol 2009; 25: 253-275.
40. Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 2004; 427: 740-744.
41. Quinones-Hinojosa A, Sanai N, Gonzalez-Perez O, Garcia-Verdugo JM. The human brain subventricular zone: stem cells in this niche and its organization. Neurosur Clin N Am 2007; 18: 15-20, vii.
42. Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 2013; 153: 1219-1227.
43. Ernst A, Alkass K, Bernard S, Salehpour M, Perl S, Tisdale J et al. Neurogenesis in the striatum of the adult human brain. Cell 2014; 156: 1072-1083.
44. Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C et al. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 2007; 315: 1243-1249.
45. Wang C, Liu F, Liu YY, Zhao CH, You Y, Wang L et al. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain. Cell Res 2011; 21: 1534-1550.
46. Clarke L, van der Kooy D. The adult mouse dentate gyrus contains populations of committed progenitor cells that are distinct from subependymal zone neural stem cells. Stem Cells 2011; 29: 1448-1458.
47. Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 2006; 26: 3-11.
48. Kyritsis N, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D et al. Acute inflammation initiates the regenerative response in the adult zebrafish brain. Science 2012; 338: 1353-1356.
49. Jakubs K, Bonde S, Iosif RE, Ekdahl CT, Kokaia Z, Kokaia M et al. Inflammation regulates functional integration of neurons born in adult brain. J Neurosci 2008; 28: 12477-12488.
50. Morrens J, Van Den Broeck W, Kempermann G. Glial cells in adult neurogenesis. Glia 2012; 60: 159-174.
51. Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA 2003; 100: 13632-13637.
52. Vallieres L, Campbell IL, Gage FH, Sawchenko PE. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 2002; 22: 486-492.
53. Ben-Hur T, Ben-Menachem O, Furer V, Einstein O, Mizrachi-Kol R, Grigoriadis N. Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells. Mol Cell Neurosci 2003; 24: 623-631.
54. Wong G, Goldshmit Y, Turnley AM. Interferon-gamma but not TNF alpha promotes neuronal differentiation and neurite outgrowth of murine adult neural stem cells. Exp Neurol 2004; 187: 171-177.
55. Bachstetter AD, Morganti JM, Jernberg J, Schlunk A, Mitchell SH, Brewster KW et al. Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats. Neurobiol Aging 2011; 32: 2030-2044.
56. Packer MA, Stasiv Y, Benraiss A, Chmielnicki E, Grinberg A, Westphal H et al. Nitric oxide negatively regulates mammalian adult neurogenesis. Proc Natl Acad Sci USA 2003; 100: 9566-9571.
57. Pluchino S, Zanotti L, Rossi B, Brambilla E, Ottoboni L, Salani G et al. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 2005; 436: 266-271.
58. Bye N, Turnley AM, Morganti-Kossmann MC. Inflammatory regulators of redirected neural migration in the injured brain. Neurosignals 2012; 20: 132-146.
59. Erlandsson A, Lin CH, Yu F, Morshead CM. Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury. Exp Neurol 2011; 230: 48-57.
60. Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 2006; 9: 268-275.
61. Iosif RE, Ahlenius H, Ekdahl CT, Darsalia V, Thored P, Jovinge S et al. Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1. J Cereb Blood Flow Metab 2008; 28: 1574-1587.
62. Iosif RE, Ekdahl CT, Ahlenius H, Pronk CJ, Bonde S, Kokaia Z et al. Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J Neurosci 2006; 26: 9703-9712.
63. Ziv Y, Avidan H, Pluchino S, Martino G, Schwartz M. Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury. Proc Natl Acad Sci USA 2006; 103: 13174-13179.
64. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003; 302: 1760-1765.
65. Bonde S, Ekdahl CT, Lindvall O. Long-term neuronal replacement in adult rat hippocampus after status epilepticus despite chronic inflammation. Eur J Neurosci 2006; 23: 965-974.
66. Aarum J, Sandberg K, Haeberlein SL, Persson MA. Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci USA 2003; 100: 15983-15988.
67. Walton NM, Sutter BM, Laywell ED, Levkoff LH, Kearns SM, Marshall II GP et al. Microglia instruct subventricular zone neurogenesis. Glia 2006; 54: 815-825.
68. Gebara E, Sultan S, Kocher-Braissant J, Toni N. Adult hippocampal neurogenesis inversely correlates with microglia in conditions of voluntary running and aging. Front Neurosci 2013; 7: 145.
69. Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 2009; 158: 1021-1029.
70. Lichtenwalner RJ, Parent JM. Adult neurogenesis and the ischemic forebrain. J Cereb Blood Flow Metab 2006; 26: 1-20.
71. Liu J, Solway K, Messing RO, Sharp FR. Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 1998; 18: 7768-7778.
72. Tsai YW, Yang YR, Wang PS, Wang RY. Intermittent hypoxia after transient focal ischemia induces hippocampal neurogenesis and c-Fos expression and reverses spatial memory deficits in rats. PloS One 2011; 6: e24001.
73. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002; 8: 963-970.
74. Tonchev AB. Brain ischemia, neurogenesis, and neurotrophic receptor expression in primates. Arch Ital Biol 2011; 149: 225-231.
75. Tonchev AB, Yamashima T, Zhao L, Okano HJ, Okano H. Proliferation of neural and neuronal progenitors after global brain ischemia in young adult macaque monkeys. Mol Cell Neurosci 2003; 23: 292-301.
76. Takagi Y, Nozaki K, Takahashi J, Yodoi J, Ishikawa M, Hashimoto N. Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice. Brain Res 1999; 831: 283-287.
77. Tureyen K, Vemuganti R, Sailor KA, Bowen KK, Dempsey RJ. Transient focal cerebral ischemia-induced neurogenesis in the dentate gyrus of the adult mouse. J Neurosurg 2004; 101: 799-805.
78. Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP et al. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA 2001; 98: 4710-4715.
79. Kee NJ, Preston E, Wojtowicz JM. Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat. Exp Brain Res 2001; 136: 313-320.
80. Yagita Y, Kitagawa K, Ohtsuki T, Takasawa K, Miyata T, Okano H et al. Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke 2001; 32: 1890-1896.
81. Takasawa K, Kitagawa K, Yagita Y, Sasaki T, Tanaka S, Matsushita K et al. Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats. J Cereb Blood Flow Metab 2002; 22: 299-307.
82. Choi YS, Lee MY, Sung KW, Jeong SW, Choi JS, Park HJ et al. Regional differences in enhanced neurogenesis in the dentate gyrus of adult rats after transient forebrain ischemia. Mol Cells 2003; 16: 232-238.
83. Tanaka R, Yamashiro K, Mochizuki H, Cho N, Onodera M, Mizuno Y et al. Neurogenesis after transient global ischemia in the adult hippocampus visualized by improved retroviral vector. Stroke 2004; 35: 1454-1459.
84. Liu XS, Chopp M, Zhang RL, Zhang ZG. MicroRNAs in cerebral ischemia-induced neurogenesis. J Neuropathol Exp Neurol 2013; 72: 718-722.
85. Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 2002; 52: 802-813.
86. Zhang RL, Chopp M, Gregg SR, Toh Y, Roberts C, Letourneau Y et al. Patterns and dynamics of subventricular zone neuroblast migration in the ischemic striatum of the adult mouse. J Cereb Blood Flow Metab 2009; 29: 1240-1250.
87. Jin K, Sun Y, Xie L, Peel A, Mao XO, Batteur S et al. Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci 2003; 24: 171-189.
88. Li Y, Yu SP, Mohamad O, Genetta T, Wei L. Sublethal transient global ischemia stimulates migration of neuroblasts and neurogenesis in mice. Transl Stroke Res 2010; 1: 184-196.
89. Thored P, Wood J, Arvidsson A, Cammenga J, Kokaia Z, Lindvall O. Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke 2007; 38: 3032-3039.
90. Liu F, You Y, Li X, Ma T, Nie Y, Wei B et al. Brain injury does not alter the intrinsic differentiation potential of adult neuroblasts. J Neurosci 2009; 29: 5075-5087.
91. Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A et al. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology 2007; 69: 1404-1410.
92. Edaravone Acute Infarction Study G. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis 2003; 15: 222-229.
93. Enlimomab Acute Stroke Trial I. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology 2001; 57: 1428-1434.
94. Bath PM, Iddenden R, Bath FJ, Orgogozo JM. Tirilazad International Steering C. Tirilazad for acute ischaemic stroke. Cochrane Database Syst Rev 2001, CD002087.
95. Krams M, Lees KR, Hacke W, Grieve AP, Orgogozo JM, Ford GA et al. Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN): an adaptive dose-response study of UK-279,276 in acute ischemic stroke. Stroke 2003; 34: 2543-2548.
96. Shuaib A, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM et al. NXY-059 for the treatment of acute ischemic stroke. N Eng J Med 2007; 357: 562-571.
97. Liu X, Xia J, Wang L, Song Y, Yang J, Yan Y et al. Efficacy and safety of ginsenoside-Rd for acute ischaemic stroke: a randomized, double-blind, placebocontrolled, phase II multicenter trial. Eur J Neurol 2009; 16: 569-575.
98. Norris JW, Hachinski VC. High dose steroid treatment in cerebral infarction. Br Med J 1986; 292: 21-23.
99. Emsley HC, Smith CJ, Georgiou RF, Vail A, Hopkins SJ, Rothwell NJ et al. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol Neurosurg Psychiatry 2005; 76: 1366-1372.
100. Lyden PD, Shuaib A, Lees KR, Davalos A, Davis SM, Diener HC et al. Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT Trial. Stroke 2007; 38: 2262-2269.
101. Pettigrew LC, Kasner SE, Albers GW, Gorman M, Grotta JC, Sherman DG et al. Safety and tolerability of arundic acid in acute ischemic stroke. J Neurol Sci 2006; 251: 50-56.
102. Xu HL, Salter-Cid L, Linnik MD, Wang EY, Paisansathan C, Pelligrino DA. Vascular adhesion protein-1 plays an important role in postischemic inflammation and neuropathology in diabetic, estrogen-treated ovariectomized female rats subjected to transient forebrain ischemia. J Pharmacol Exp Ther 2006; 317: 19-29.
103. Hodges H, Sowinski P, Virley D, Nelson A, Kershaw TR, Watson WP et al. Functional reconstruction of the hippocampus: fetal versus conditionally immortal neuroepithelial stem cell grafts. Novartis Found Symp 2000; 231: 53-65, discussion 65-9.
104. Hodges H, Veizovic T, Bray N, French SJ, Rashid TP, Chadwick A et al. Conditionally immortal neuroepithelial stem cell grafts reverse age-associated memory impairments in rats. Neuroscience 2000; 101: 945-955.
105. Qu T, Brannen CL, Kim HM, Sugaya K. Human neural stem cells improve cognitive function of aged brain. Neuroreport 2001; 12: 1127-1132.
106. Park DH, Eve DJ, Sanberg PR, Musso 3rd J, Bachstetter AD, Wolfson A et al. Increased neuronal proliferation in the dentate gyrus of aged rats following neural stem cell implantation. Stem Cells Dev 2010; 19: 175-180.
107. Roy NS, Benraiss A, Wang S, Fraser RA, Goodman R, Couldwell WT et al. Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone. J Neurosci Res 2000; 59: 321-331.
108. Hallbergson AF, Gnatenco C, Peterson DA. Neurogenesis and brain injury: managing a renewable resource for repair. J Clin Investig 2003; 112: 1128-1133.
109. Nakashiba T, Cushman JD, Pelkey KA, Renaudineau S, Buhl DL, McHugh TJ et al. Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell 2012; 149: 188-201.
110. Ge S, Yang CH, Hsu KS, Ming GL, Song H. A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 2007; 54: 559-566.
111. Mongiat LA, Esposito MS, Lombardi G, Schinder AF. Reliable activation of immature neurons in the adult hippocampus. PloS One 2009; 4: e5320.
112. Schmidt-Hieber C, Jonas P, Bischofberger J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 2004; 429: 184-187.
113. Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN et al. Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 1997; 28: 1233-1244.
114. Lambertsen KL, Clausen BH, Babcock AA, Gregersen R, Fenger C, Nielsen HH et al. Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. J Neurosci 2009; 29: 1319-1330.
115. Clausen BH, Lambertsen KL, Babcock AA, Holm TH, Dagnaes-Hansen F, Finsen B. Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice. J Neuroinflammation 2008; 5: 46.
116. Ohtaki H, Yin L, Nakamachi T, Dohi K, Kudo Y, Makino R et al. Expression of tumor necrosis factor alpha in nerve fibers and oligodendrocytes after transient focal ischemia in mice. Neurosci Lett 2004; 368: 162-166.
117. Wang X, Yue TL, Barone FC, White RF, Gagnon RC, Feuerstein GZ. Concomitant cortical expression of TNF-alpha and IL-1 beta mRNAs follows early response gene expression in transient focal ischemia. Mol Chem Neuropathol 1994; 23: 103-114.
118. Boutin H, LeFeuvre RA, Horai R, Asano M, Iwakura Y, Rothwell NJ. Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci 2001; 21: 5528-5534.
119. Berti R, Williams AJ, Moffett JR, Hale SL, Velarde LC, Elliott PJ et al. Quantitative real-time RT-PCR analysis of inflammatory gene expression associated with ischemia-reperfusion brain injury. J Cereb Blood Flow Metab 2002; 22: 1068-1079.
120. Herrmann O, Tarabin V, Suzuki S, Attigah N, Coserea I, Schneider A et al. Regulation of body temperature and neuroprotection by endogenous interleukin-6 in cerebral ischemia. J Cereb Blood Flow Metab 2003; 23: 406-415.
121. Loddick SA, Turnbull AV, Rothwell NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 1998; 18: 176-179.
122. Yamashita T, Sawamoto K, Suzuki S, Suzuki N, Adachi K, Kawase T et al. Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice: possible involvement of Stat3 activation in the protection of neurons. J Neurochem 2005; 94: 459-468.
123. Mukaida N, Matsumoto T, Yokoi K, Harada A, Matsushima K. Inhibition of neutrophil-mediated acute inflammation injury by an antibody against interleukin-8 (IL-8). Inflamm Res 1998; 47(Suppl 3): S151-S157.
124. Kostulas N, Pelidou SH, Kivisakk P, Kostulas V, Link H. Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study. Stroke 1999; 30: 2174-2179.
125. Konoeda F, Shichita T, Yoshida H, Sugiyama Y, Muto G, Hasegawa E et al. Therapeutic effect of IL-12/23 and their signaling pathway blockade on brain ischemia model. Biochem Biophys Res Commun 2010; 402: 500-506.
126. Yilmaz G, Arumugam TV, Stokes KY, Granger DN. Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 2006; 113: 2105-2112.
127. Yasuda Y, Shimoda T, Uno K, Tateishi N, Furuya S, Tsuchihashi Y et al. Temporal and sequential changes of glial cells and cytokine expression during neuronal degeneration after transient global ischemia in rats. J Neuroinflammation 2011; 8: 70.
128. Iadecola C, Zhang F, Casey R, Nagayama M, Ross ME. Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene. J Neurosci 1997; 17: 9157-9164.
129. Iadecola C, Zhang F, Casey R, Clark HB, Ross ME. Inducible nitric oxide synthase gene expression in vascular cells after transient focal cerebral ischemia. Stroke 1996; 27: 1373-1380.
130. Gidday JM, Gasche YG, Copin JC, Shah AR, Perez RS, Shapiro SD et al. Leukocytederived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am J Physiology Heart Circ Physiol 2005; 289: H558-H568.
131. Wang G, Guo Q, Hossain M, Fazio V, Zeynalov E, Janigro D et al. Bone marrowderived cells are the major source of MMP-9 contributing to blood-brain barrier dysfunction and infarct formation after ischemic stroke in mice. Brain Res 2009; 1294: 183-192.
132. Montaner J, Alvarez-Sabin J, Molina C, Angles A, Abilleira S, Arenillas J et al. Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke 2001; 32: 1759-1766.
133. Shimakura A, Kamanaka Y, Ikeda Y, Kondo K, Suzuki Y, Umemura K. Neutrophil elastase inhibition reduces cerebral ischemic damage in the middle cerebral artery occlusion. Brain Res 2000; 858: 55-60.
134. Stowe AM, Adair-Kirk TL, Gonzales ER, Perez RS, Shah AR, Park TS et al. Neutrophil elastase and neurovascular injury following focal stroke and reperfusion. Neurobiol Dis 2009; 35: 82-90.
135. de Bilbao F, Arsenijevic D, Moll T, Garcia-Gabay I, Vallet P, Langhans W et al. In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice. J Neurochem 2009; 110: 12-22.
136. Grilli M, Barbieri I, Basudev H, Brusa R, Casati C, Lozza G et al. Interleukin-10 modulates neuronal threshold of vulnerability to ischaemic damage. Eur J Neurosci 2000; 12: 2265-2272.
137. Ooboshi H, Ibayashi S, Shichita T, Kumai Y, Takada J, Ago T et al. Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia. Circulation 2005; 111: 913-919.
138. Quirie A, Demougeot C, Bertrand N, Mossiat C, Garnier P, Marie C et al. Effect of stroke on arginase expression and localization in the rat brain. Eur J Neurosci 2013; 37: 1193-1202.
139. Henrich-Noack P, Prehn JH, Krieglstein J. TGF-beta 1 protects hippocampal neurons against degeneration caused by transient global ischemia. Doseresponse relationship and potential neuroprotective mechanisms. Stroke 1996; 27: 1609-1614, discussion 1615.
140. Ruocco A, Nicole O, Docagne F, Ali C, Chazalviel L, Komesli S et al. A transforming growth factor-beta antagonist unmasks the neuroprotective role of this endogenous cytokine in excitotoxic and ischemic brain injury. J Cereb Blood Flow Metab 1999; 19: 1345-1353.
141. Zhu Y, Yang GY, Ahlemeyer B, Pang L, Che XM, Culmsee C et al. Transforming growth factor-beta 1 increases bad phosphorylation and protects neurons against damage. J Neurosci 2002; 22: 3898-3909.
142. Lehrmann E, Kiefer R, Finsen B, Diemer NH, Zimmer J, Hartung HP. Cytokines in cerebral ischemia: expression of transforming growth factor beta-1 (TGF-beta 1) mRNA in the postischemic adult rat hippocampus. Exp Neurol 1995; 131: 114-123.
143. Wang X, Yue TL, White RF, Barone FC, Feuerstein GZ. Transforming growth factor-beta 1 exhibits delayed gene expression following focal cerebral ischemia. Brain Res Bull 1995; 36: 607-609.
144. Peters O, Back T, Lindauer U, Busch C, Megow D, Dreier J et al. Increased formation of reactive oxygen species after permanent and reversible middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 1998; 18: 196-205.
145. Piantadosi CA, Zhang J. Mitochondrial generation of reactive oxygen species after brain ischemia in the rat. Stroke 1996; 27: 327-331, discussion 332.
146. Kunz A, Anrather J, Zhou P, Orio M, Iadecola C. Cyclooxygenase-2 does not contribute to postischemic production of reactive oxygen species. J Cereb Blood Flow Metab 2007; 27: 545-551.
147. Dirnagl U, Lindauer U, Them A, Schreiber S, Pfister HW, Koedel U et al. Global cerebral ischemia in the rat: online monitoring of oxygen free radical production using chemiluminescence in vivo. J Cereb Blood Flow Metabol 1995; 15: 929-940.
148. Takizawa S, Aratani Y, Fukuyama N, Maeda N, Hirabayashi H, Koyama H et al. Deficiency of myeloperoxidase increases infarct volume and nitrotyrosine formation in mouse brain. J Cereb Blood Flow Metab 2002; 22: 50-54.
149. Breckwoldt MO, Chen JW, Stangenberg L, Aikawa E, Rodriguez E, Qiu S et al. Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci USA 2008; 105: 18584-18589.
150. van Breda EJ, van der Worp HB, van Gemert HM, Algra A, Kappelle LJ, van Gijn J et al. PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial [ISCRTN 74418480]. BMC Cardiovasc Disord 2005; 5: 24.