Top

Published in:

01-06-2010 | ORIGINAL ARTICLE

Implications of Immune System in Stroke for Novel Therapeutic Approaches

Authors: Aaron A. Hall, Keith R. Pennypacker

Published in: Translational Stroke Research | Issue 2/2010

Abstract

Each year, approximately 795,000 people suffer a new or recurrent stroke. About 610,000 of these are first attacks, and 185,000 are recurrent attacks. Currently, the only FDA approved treatment for ischemic stroke is the thrombolytic recombinant tissue plasminogen activator (Alteplase), which must be given within 4.5 h of stroke onset. Beyond this time, apoptotic and inflammatory processes greatly diminish the therapeutic benefits of current treatments. While there have been many experimental treatments for stroke that showed promising preclinical efficacy, these treatments have failed to show efficacy in clinical trials. In many of these cases, the preclinical animal studies did not model the clinical setting effectively. The injury that occurs following stroke is a dynamic process. To effectively treat stroke patients at clinically relevant timepoints, it is imperative to understand both the humeral and cell-mediated phenomena that occur throughout the body in response to ischemic injury over time. Promising experimental therapeutics designed to be given 1 to 2 days following stroke require both neuroprotective and anti-inflammatory properties in order to be efficacious.

Carandang R, Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Kannel WB et al (2006) Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years. JAMA 296(24):2939–2946PubMed

Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K et al (2009) Heart disease and stroke statistics—2009 update: a report from the American heart association statistics committee and stroke statistics subcommittee. Circulation 119(3):480–486PubMed

Norrving B (2008) Lacunar infarcts: no black holes in the brain are benign. Pract Neurol 8(4):222–228PubMed

Sacco S, Marini C, Totaro R, Russo T, Cerone D, Carolei A (2006) A population-based study of the incidence and prognosis of lacunar stroke. Neurology 66(9):1335–1338PubMed

Bejot Y, Catteau A, Caillier M, Rouaud O, Durier J, Marie C et al (2008) Trends in incidence, risk factors, and survival in symptomatic lacunar stroke in Dijon, France, from 1989 to 2006: a population-based study. Stroke 39(7):1945–1951PubMed

Schwamm LH, Koroshetz WJ, Sorensen AG, Wang B, Copen WA, Budzik R et al (1998) Time course of lesion development in patients with acute stroke: serial diffusion- and hemodynamic-weighted magnetic resonance imaging. Stroke 29(11):2268–2276PubMed

Newcomb JD, Ajmo CT, Sanberg CD, Sanberg PR, Pennypacker KR, Willing AE (2006) Timing of cord blood treatment after experimental stroke determine therapeutic efficacy. Cell Transplant 15(3):213–223PubMed

Baron JC (2001) Mapping the ischaemic penumbra with PET: a new approach. Brain 124(Pt 1):2–4PubMed

Baron JC. Stroke: imaging and differential diagnosis. J Neural Transm. 2002;(63):19–36.

10.

Hagberg H, Peebles D, Mallard C (2002) Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults. Ment Retard Dev Disabil Res Rev 8(1):30–38PubMed

11.

Dewar D, Yam P, McCulloch J (1999) Drug development for stroke: importance of protecting cerebral white matter. Eur J Pharmacol 375(1–3):41–50PubMed

12.

Dawes H, Enzinger C, Johansen-Berg H, Bogdanovic M, Guy C, Collett J et al (2008) Walking performance and its recovery in chronic stroke in relation to extent of lesion overlap with the descending motor tract. Exp Brain Res 186(2):325–333PubMed

13.

Pineiro R, Pendlebury ST, Smith S, Flitney D, Blamire AM, Styles P et al (2000) Relating MRI changes to motor deficit after ischemic stroke by segmentation of functional motor pathways. Stroke 31(3):672–679PubMed

14.

Dirnagl U, Iadecola C, Moskowitz M (1999) Pathobiology of ischemic stroke: an integrated view. TINS 22(9):391–397PubMed

15.

Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G et al (2000) Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31(2):347–354PubMed

16.

Elting JW, Sulter GA, Kaste M, Lees KR, Diener HC, Hommel M et al (2002) AMPA antagonist ZK200775 in patients with acute ischemic stroke: possible glial cell toxicity detected by monitoring of S-100B serum levels. Stroke 33(12):2813–2818PubMed

17.

Limburg M, Hijdra A (1990) Flunarizine in acute ischemic stroke: a pilot study. Eur Neurol 30(3):121–122PubMed

18.

Lyden P, Jacoby M, Schim J, Albers G, Mazzeo P, Ashwood T et al (2001) The clomethiazole acute stroke study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results. Neurology 57(7):1199–1205PubMed

19.

Diener HC, Cortens M, Ford G, Grotta J, Hacke W, Kaste M et al (2000) Lubeluzole in acute ischemic stroke treatment: a double-blind study with an 8-hour inclusion window comparing a 10-mg daily dose of lubeluzole with placebo. Stroke 31(11):2543–2551PubMed

20.

Horn J, de Haan RJ, Vermeulen M, Luiten PG, Limburg M (2001) Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review. Stroke 32(10):2433–2438PubMed

21.

Mulley G, Wilcox RG, Mitchell JR (1978) Dexamethasone in acute stroke. Br Med J 2(6143):994–996PubMed

22.

Enlimomab Acute Stroke Trial Investigators (2001) Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology 57(8):1428–1434

23.

Hu23F2G. 23F2G, LeukArrest. Drugs R D. 1999;1(1):25–26

24.

Lees KR, Diener HC, Asplund K, Krams M (2003) UK-279, 276, a neutrophil inhibitory glycoprotein, in acute stroke: tolerability and pharmacokinetics. Stroke 34(7):1704–1709PubMed

25.

Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568PubMed

26.

Obrenovitch TP (2008) Molecular physiology of preconditioning-induced brain tolerance to ischemia. Physiol Rev 88(1):211–247PubMed

27.

Takano K, Latour LL, Formato JE, Carano RA, Helmer KG, Hasegawa Y et al (1996) The role of spreading depression in focal ischemia evaluated by diffusion mapping. Ann Neurol 39(3):308–318PubMed

28.

Streit WJ, Mrak RE, Griffin WS (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation 1(1):14PubMed

29.

Streit WJ, Conde JR, Fendrick SE, Flanary BE, Mariani CL (2005) Role of microglia in the central nervous system's immune response. Neurol Res 27(7):685–691PubMed

30.

Davalos D, Grutzendler J, Yang GJVK, Zuo Y, Jung S et al (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nature Neurosci 8:752–758PubMed

31.

Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB et al (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9(12):1512–1519PubMed

32.

van Landeghem FK, Stover JF, Bechmann I, Bruck W, Unterberg A, Buhrer C et al (2001) Early expression of glutamate transporter proteins in ramified microglia after controlled cortical impact injury in the rat. Glia 35(3):167–179PubMed

33.

Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K et al (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438(7070):1017–1021PubMed

34.

Lehrmann E, Kiefer R, Christensen T, Toyka KV, Zimmer J, Diemer NH et al (1998) Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats. Glia 24(4):437–448PubMed

35.

da Cunha A, Jefferson JJ, Tyor WR, Glass JD, Jannotta FS, Cottrell JR et al (1997) Transforming growth factor-beta1 in adult human microglia and its stimulated production by interleukin-1. J Interferon Cytokine Res 17(11):655–664PubMed

36.

Garden GA, Moller T (2006) Microglia biology in health and disease. J Neuroimmune Pharmacol 1(2):127–137PubMed

37.

Gibson CL, Coughlan TC, Murphy SP (2005) Glial nitric oxide and ischemia. Glia 50(4):417–426PubMed

38.

Allan SM, Rothwell NJ (2001) Cytokines and acute neurodegeneration. Nat Rev Neurosci 2(10):734–744PubMed

39.

Lalancette-Hebert M, Gowing G, Simard A, Weng YC, Kriz J (2007) Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J Neurosci 27(10):2596–2605PubMed

40.

Jara JH, Singh BB, Floden AM, Combs CK (2007) Tumor necrosis factor alpha stimulates NMDA receptor activity in mouse cortical neurons resulting in ERK-dependent death. J Neurochem 100(5):1407–1420PubMed

41.

Thornton P, Pinteaux E, Gibson RM, Allan SM, Rothwell NJ (2006) Interleukin-1-induced neurotoxicity is mediated by glia and requires caspase activation and free radical release. J Neurochem 98(1):258–266PubMed

42.

Relton J, Martin D, Thompson R, Russell D (1996) Peripheral administration of interleukin-1 receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat. Exp Neurol 138:206–213PubMed

43.

Lambertsen KL, Clausen BH, Babcock AA, Gregersen R, Fenger C, Nielsen HH et al (2009) Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. J Neurosci 29(5):1319–1330PubMed

44.

Zheng Z, Yenari MA (2004) Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol Res 26(8):884–892PubMed

45.

Offner H, Subramanian S, Parker SM, Wang C, Afentoulis ME, Lewis A et al (2006) Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. J Immunol 176(11):6523–6531PubMed

46.

Chrousos GP (1995) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 332(20):1351–1362PubMed

47.

Chrousos GP (1992) Regulation and dysregulation of the hypothalamic-pituitary-adrenal axis. The corticotropin-releasing hormone perspective. Endocrinol Metab Clin North Am 21(4):833–858PubMed

48.

Saper CB, Loewy AD, Swanson LW, Cowan WM (1976) Direct hypothalamo-autonomic connections. Brain Res 117(2):305–312PubMed

49.

Chamorro A, Amaro S, Vargas M, Obach V, Cervera A, Gomez-Choco M et al (2007) Catecholamines, infection, and death in acute ischemic stroke. J Neurol Sci 252(1):29–35PubMed

50.

Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES (2000) The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52(4):595–638PubMed

51.

Anagnostou VK, Doussis-Anagnostopoulou I, Tiniakos DG, Karandrea D, Agapitos E, Karakitsos P et al (2007) Ontogeny of intrinsic innervation in the human thymus and spleen. J Histochem Cytochem 55(8):813–820PubMed

52.

Vendrame M, Gemma C, Pennypacker KR, Bickford PC, Davis Sanberg C, Sanberg PR et al (2006) Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp Neurol 199(1):191–200PubMed

53.

Yilmaz G, Arumugam TV, Stokes KY, Granger DN (2006) Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 113(17):2105–2112PubMed

54.

Prass K, Meisel C, Hoflich C, Braun J, Halle E, Wolf T et al (2003) Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med 198(5):725–736PubMed

55.

Meisel C, Schwab JM, Prass K, Meisel A, Dirnagl U (2005) Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci 6(10):775–786PubMed

56.

Prass K, Braun JS, Dirnagl U, Meisel C, Meisel A (2006) Stroke propagates bacterial aspiration to pneumonia in a model of cerebral ischemia. Stroke 37(10):2607–2612PubMed

57.

Ajmo CT Jr, Collier LA, Leonardo CC, Hall AA, Green SM, Womble TA et al (2009) Blockade of adrenoreceptors inhibits the splenic response to stroke. Exp Neurol 218(1):47–55PubMed

58.

Klehmet J, Harms H, Richter M, Prass K, Volk HD, Dirnagl U et al (2009) Stroke-induced immunodepression and post-stroke infections: lessons from the preventive antibacterial therapy in stroke trial. Neuroscience 158(3):1184–1193PubMed

59.

Urra X, Cervera A, Villamor N, Planas AM, Chamorro A (2009) Harms and benefits of lymphocyte subpopulations in patients with acute stroke. Neuroscience 158(3):1174–1183PubMed

60.

Aslanyan S, Weir CJ, Diener HC, Kaste M, Lees KR (2004) Pneumonia and urinary tract infection after acute ischaemic stroke: a tertiary analysis of the GAIN International trial. Eur J Neurol 11(1):49–53PubMed

61.

Vendrame M, Cassady CJ, Newcomb J, Butler T, Pennypacker KR, Zigova T et al (2004) Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume. Stroke 35:2390–2395PubMed

62.

Willing AE, Lixian J, Milliken M, Poulos S, Zigova T, Song S et al (2003) Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J Neurosci Res 73(3):296–307PubMed

63.

Okuaki Y, Miyazaki H, Zeniya M, Ishikawa T, Ohkawa Y, Tsuno S et al (1996) Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat. Liver 16(3):188–194PubMed

64.

Savas MC, Ozguner M, Ozguner IF, Delibas N (2003) Splenectomy attenuates intestinal ischemia-reperfusion-induced acute lung injury. J Pediatr Surg 38(10):1465–1470PubMed

65.

Jiang H, Meng F, Li W, Tong L, Qiao H, Sun X (2007) Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats. Surgery 141(1):32–40PubMed

66.

Ajmo CT Jr, Vernon DO, Collier L, Hall AA, Garbuzova-Davis S, Willing A et al (2008) The spleen contributes to stroke-induced neurodegeneration. J Neurosci Res 86:2227–2234PubMed

67.

Lindsberg PJ, Carpen O, Paetau A, Karjalainen-Lindsberg ML, Kaste M (1996) Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation 94(5):939–945PubMed

68.

Wang X, Siren AL, Liu Y, Yue TL, Barone FC, Feuerstein GZ (1994) Upregulation of intercellular adhesion molecule 1 (ICAM-1) on brain microvascular endothelial cells in rat ischemic cortex. Brain Res Mol Brain Res 26(1–2):61–68PubMed

69.

Kochanek PM, Hallenbeck JM (1992) Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23(9):1367–1379PubMed

70.

Jean WC, Spellman SR, Nussbaum ES, Low WC (1998) Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon. Neurosurgery 43(6):1382–1396 discussion 96-7PubMed

71.

Matsuo Y, Onodera H, Shiga Y, Nakamura M, Ninomiya M, Kihara T et al (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 25(7):1469–1475PubMed

72.

Overall CM, McQuibban GA, Clark-Lewis I (2002) Discovery of chemokine substrates for matrix metalloproteinases by exosite scanning: a new tool for degradomics. Biol Chem 383(7–8):1059–1066PubMed

73.

Schonbeck U, Mach F, Libby P (1998) Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1 beta processing. J Immunol 161(7):3340–3346PubMed

74.

Gearing AJ, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH et al (1994) Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature 370(6490):555–557PubMed

75.

Kitamura Y, Shimohama S, Ota T, Matsuoka Y, Nomura Y, Taniguchi T (1997) Alteration of transcription factors NF-kappaB and STAT1 in Alzheimer's disease brains. Neurosci Lett 237(1):17–20PubMed

76.

Lagasse E, Weissman IL (1994) bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages. J Exp Med 179(3):1047–1052PubMed

77.

Weston RM, Jones NM, Jarrott B, Callaway JK (2007) Inflammatory cell infiltration after endothelin-1-induced cerebral ischemia: histochemical and myeloperoxidase correlation with temporal changes in brain injury. J Cereb Blood Flow Metab 27(1):100–114PubMed

78.

Meszaros AJ, Reichner JS, Albina JE (1999) Macrophage phagocytosis of wound neutrophils. J Leukoc Biol 65(1):35–42PubMed

79.

Wang X, Yue TL, Barone FC, Feuerstein GZ (1995) Monocyte chemoattractant protein-1 messenger RNA expression in rat ischemic cortex. Stroke 26(4):661–665; discussion 5–6PubMed

80.

Gourmala NG, Buttini M, Limonta S, Sauter A, Boddeke HW (1997) Differential and time-dependent expression of monocyte chemoattractant protein-1 mRNA by astrocytes and macrophages in rat brain: effects of ischemia and peripheral lipopolysaccharide administration. J Neuroimmunol 74(1–2):35–44PubMed

81.

Che X, Ye W, Panga L, Wu DC, Yang GY (2001) Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice. Brain Res 902(2):171–177PubMed

82.

Sheehan JJ, Zhou C, Gravanis I, Rogove AD, Wu YP, Bogenhagen DF et al (2007) Proteolytic activation of monocyte chemoattractant protein-1 by plasmin underlies excitotoxic neurodegeneration in mice. J Neurosci 27(7):1738–1745PubMed

83.

Yamagami S, Tamura M, Hayashi M, Endo N, Tanabe H, Katsuura Y et al (1999) Differential production of MCP-1 and cytokine-induced neutrophil chemoattractant in the ischemic brain after transient focal ischemia in rats. J Leukoc Biol 65(6):744–749PubMed

84.

Giunti S, Pinach S, Arnaldi L, Viberti G, Perin PC, Camussi G et al (2006) The MCP-1/CCR2 system has direct proinflammatory effects in human mesangial cells. Kidney Int 69(5):856–863PubMed

85.

Viedt C, Dechend R, Fei J, Hansch GM, Kreuzer J, Orth SR (2002) MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-kappaB and activating protein-1. J Am Soc Nephrol 13(6):1534–1547PubMed

86.

Stoll G, Jander S, Schroeter M (1998) Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56:149–171PubMed

87.

Kleinschnitz C, Bendszus M, Frank M, Solymosi L, Toyka KV, Stoll G (2003) In vivo monitoring of macrophage infiltration in experimental ischemic brain lesions by magnetic resonance imaging. J Cereb Blood Flow Metab 23(11):1356–1361PubMed

88.

Jander S, Schroeter M, D'Urso D, Gillen C, Witte OW, Stoll G (1998) Focal ischaemia of the rat brain elicits an unusual inflammatory response: early appearance of CD8+ macrophages/microglia. Eur J NeuroSci 10(2):680–688PubMed

89.

Schilling M, Besselmann M, Muller M, Strecker JK, Ringelstein EB, Kiefer R (2005) 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 196(2):290–297PubMed

90.

Schroeter M, Jander S, Huitinga I, Witte OW, Stoll G (1997) Phagocytic response in photochemically induced infarction of rat cerebral cortex. The role of resident microglia. Stroke 28(2):382–386PubMed

91.

Petroff OA, Graham GD, Blamire AM, al-Rayess M, Rothman DL, Fayad PB et al (1992) Spectroscopic imaging of stroke in humans: histopathology correlates of spectral changes. Neurology 42(7):1349–1354PubMed

92.

Kotter MR, Setzu A, Sim FJ, Van Rooijen N, Franklin RJ (2001) Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia 35(3):204–212PubMed

93.

Frenkel D, Huang Z, Maron R, Koldzic DN, Hancock WW, Moskowitz MA et al (2003) Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+ T cells. J Immunol 171(12):6549–6555PubMed

94.

Gee JM, Kalil A, Thullbery M, Becker KJ (2008) Induction of immunologic tolerance to myelin basic protein prevents central nervous system autoimmunity and improves outcome after stroke. Stroke 39(5):1575–1582PubMed

95.

Harling-Berg CJ, Park TJ, Knopf PM (1999) Role of the cervical lymphatics in the Th2-type hierarchy of CNS immune regulation. J Neuroimmunol 101(2):111–127PubMed

96.

Marler JR, Goldstein LB (2003) Medicine. Stroke—tPA and the clinic. Science 301(5640):1677PubMed

97.

Teesalu T, Kulla A, Asser T, Koskiniemi M, Vaheri A (2002) Tissue plasminogen activator as a key effector in neurobiology and neuropathology. Biochem Soc Trans 30(2):183–189PubMed

98.

Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P (2004) Antithrombotic and thrombolytic therapy for ischemic stroke: the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126(3 Suppl):483S–512SPubMed

99.

Toni D, Fiorelli M, Bastianello S, Sacchetti ML, Sette G, Argentino C et al (1996) Hemorrhagic transformation of brain infarct: predictability in the first 5 hours from stroke onset and influence on clinical outcome. Neurology 46(2):341–345PubMed

100.

Cuadrado E, Ortega L, Hernandez-Guillamon M, Penalba A, Fernandez-Cadenas I, Rosell A et al (2008) Tissue plasminogen activator (t-PA) promotes neutrophil degranulation and MMP-9 release. J Leukoc Biol 84(1):207–214PubMed

101.

Noser EA, Shaltoni HM, Hall CE, Alexandrov AV, Garami Z, Cacayorin ED et al (2005) Aggressive mechanical clot disruption: a safe adjunct to thrombolytic therapy in acute stroke? Stroke 36(2):292–296PubMed

102.

Kim D, Jahan R, Starkman S, Abolian A, Kidwell CS, Vinuela F et al (2006) Endovascular mechanical clot retrieval in a broad ischemic stroke cohort. AJNR Am J Neuroradiol 27(10):2048–2052PubMed

103.

Garbuzova-Davis S, Willing A, Zigova T, Saporta S, Justen EB, Lane JC et al (2003) Intravenous adminstration of human umbilical cord blood cells in a mouse model of amyotrohic lateral sclerosis: distribution, migration, and differentiation. J Hematother Stem Cell Res 12:255–270PubMed

104.

Nikolic WV, Hou H, Town T, Zhu Y, Giunta B, Sanberg CD et al (2008) Peripherally administered human umbilical cord blood cells reduce parenchymal and vascular beta-amyloid deposits in Alzheimer mice. Stem Cells Dev 17(3):423–439PubMed

105.

Ende N, Chen R (2002) Parkinson's disease mice and human umbilical cord blood. J Med 33(1–4):173–180PubMed

106.

Saporta S, Kim JJ, Willing AE, Fu ES, Davis CD, Sanberg PR (2003) Human umbilical cord blood stem cells infusion in spinal cord injury: engraftment and beneficial influence on behavior. J Hematother Stem Cell Res 12(3):271–278PubMed

107.

Ajmo C Jr, Vernon D, Collier L, Pennypacker K, Cuevas J (2006) Sigma receptor activation reduces infarct size at 24 hours after permanent middle cerebral artery occlusion in rats. Cur Neurovascular Res 3(2):89–98

108.

Quirion R, Bowen WD, Itzhak Y, Junien J, Musacchio JM, Rothman RB et al (1992) A proposal for the classification of sigma binding sites. Trends Pharmacol Sci 13:85–86PubMed

109.

Seth P, Fei YJ, Li HW, Huang W, Leibach FH, Ganapathy V (1998) Cloning and functional characterization of a sigma receptor from rat brain. J Neurochem 70:922–931PubMedCrossRef

110.

Hayashi T, Su T (2001) Regulating ankyrin dynamics: roles of sigma-1 receptors. Proc Natl Acad Sci USA 98(2):491–496PubMed

111.

Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE (2009) The hallucinogen N, N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science 323(5916):934–937PubMed

112.

Su TP, Shukla K, Gund T (1990) Steroid binding at sigma receptors: CNS and immunological implications. Ciba Found Symp 153:107–113; discussion 13-6PubMed

113.

Shen YC, Wang YH, Chou YC, Liou KT, Yen JC, Wang WY et al (2008) Dimemorfan protects rats against ischemic stroke through activation of sigma-1 receptor-mediated mechanisms by decreasing glutamate accumulation. J Neurochem 104(2):558–572PubMed

114.

Takahashi H, Traystman RJ, Hashimoto K, London ED, Kirsch JR (1997) Postischemic brain injury is affected stereospecifically by pentazocine in rats. Anesth Analg 85(2):353–357PubMed

115.

Takahashi H, Kirsch JR, Hashimoto K, London ED, Koehler RC, Traystman RJ (1996) PPBP [4-phenyl-1-(4-phenylbutyl) piperidine] decreases brain injury after transient focal ischemia in rats. Stroke 27(11):2120–2123PubMed

116.

Ajmo CT Jr, Vernon DO, Collier L, Pennypacker KR, Cuevas J (2006) Sigma receptor activation reduces infarct size at 24 hours after permanent middle cerebral artery occlusion in rats. Curr Neurovasc Res 3(2):89–98PubMed

117.

Su TP, London E, Jaffe JH (1988) Steroid binding at sigma receptors suggests a link between endocrine, nervous, and immune systems. Science 240(4937):1635–1638

118.

Zhu LX, Sharma S, Gardner B, Escuadro B, Atianzar K, Tashkin DP et al (2003) IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity. J Immunol 170:3585–3591PubMed

119.

Carr DJ, De Costa BR, Radesca L, Blalock JE (1991) Functional assessment and partial characterization of [3H](+)-pentazocine binding sites on cells of the immune system. J Neuroimmunol 35:153–166PubMed

120.

Bourrie B, Bribes E, De Nys N, Esclangon M, Garcia L, Galiegue S et al (2002) SSR125329A, a high affinity sigma receptor ligand with potent anti-inflammatory properties. Eur J Pharmacol 456(1–3):123–131PubMed

121.

Gannon CJ, Malone DL, Napolitano LM (2001) Reduction of IL-10 and nitric oxide synthesis by SR31747A (sigma ligand) in RAW murine macrophages. Surg Infect 2(4):267–272

122.

Gekker G, Hu S, Sheng WS, Rock RB, Lokensgard JR, Peterson PK (2006) Cocaine-induced HIV-1 expression in microglia involves sigma-1 receptors and transforming growth factor-beta1. Int Immunopharmacol 6(6):1029–1033PubMed

123.

Katnik C, Guerrero WR, Pennypacker KR, Herrera Y, Cuevas J (2006) Sigma-1 receptor activation prevents intracellular calcium dysregulation in cortical neurons during in vitro ischemia. J Pharmacol Exp Ther 319(3):1355–1365PubMed

124.

Herrera Y, Katnik C, Rodriguez JD, Hall AA, Willing A, Pennypacker KR et al (2008) sigma-1 receptor modulation of acid-sensing ion channel a (ASIC1a) and ASIC1a-induced Ca2+ influx in rat cortical neurons. J Pharmacol Exp Ther 327(2):491–502PubMed

125.

Xiong ZG, Chu XP, Simon RP (2007) Acid sensing ion channels—novel therapeutic targets for ischemic brain injury. Front Biosci 12:1376–1386PubMed

126.

Xiong ZG, Pignataro G, Li M, Chang SY, Simon RP (2008) Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases. Curr Opin Pharmacol 8(1):25–32PubMed

127.

Yu YM, Kim JB, Lee KW, Kim SY, Han PL, Lee JK (2005) Inhibition of the cerebral ischemic injury by ethyl pyruvate with a wide therapeutic window. Stroke 36(10):2238–2243PubMed

128.

Sehara Y, Hayashi T, Deguchi K, Zhang H, Tsuchiya A, Yamashita T et al (2007) Decreased focal inflammatory response by G-CSF may improve stroke outcome after transient middle cerebral artery occlusion in rats. J Neurosci Res 85(10):2167–2174PubMed

Title: Implications of Immune System in Stroke for Novel Therapeutic Approaches
Authors: Aaron A. Hall
Keith R. Pennypacker
Publication date: 01-06-2010
Publisher: Springer-Verlag
Published in: Translational Stroke Research / Issue 2/2010
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-009-0003-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Implications of Immune System in Stroke for Novel Therapeutic Approaches

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2010

Translational Stroke Research Using a Rabbit Embolic Stroke Model: A Correlative Analysis Hypothesis for Novel Therapy Development

Magnesium Sulfate Treatment Improves Outcome in Patients with Subarachnoid Hemorrhage: A Meta-analysis Study

Administration of a Sigma Receptor Agonist Delays MCAO-Induced Neurodegeneration and White Matter Injury

Association Between Changes in Weight and Cerebral Arteries in Rats

Ccm1 Assures Microvascular Integrity During Angiogenesis

Inflammation After Stroke: Mechanisms and Therapeutic Approaches