Skip to main content
Erschienen in: Translational Stroke Research 2/2010

01.06.2010 | ORIGINAL ARTICLE

Implications of Immune System in Stroke for Novel Therapeutic Approaches

verfasst von: Aaron A. Hall, Keith R. Pennypacker

Erschienen in: Translational Stroke Research | Ausgabe 2/2010

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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 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
2.
Zurück zum Zitat 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 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
3.
Zurück zum Zitat Norrving B (2008) Lacunar infarcts: no black holes in the brain are benign. Pract Neurol 8(4):222–228PubMed Norrving B (2008) Lacunar infarcts: no black holes in the brain are benign. Pract Neurol 8(4):222–228PubMed
4.
Zurück zum Zitat 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 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
5.
Zurück zum Zitat 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 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
6.
Zurück zum Zitat 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 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
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat Baron JC (2001) Mapping the ischaemic penumbra with PET: a new approach. Brain 124(Pt 1):2–4PubMed Baron JC (2001) Mapping the ischaemic penumbra with PET: a new approach. Brain 124(Pt 1):2–4PubMed
9.
Zurück zum Zitat Baron JC. Stroke: imaging and differential diagnosis. J Neural Transm. 2002;(63):19–36. Baron JC. Stroke: imaging and differential diagnosis. J Neural Transm. 2002;(63):19–36.
10.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Dirnagl U, Iadecola C, Moskowitz M (1999) Pathobiology of ischemic stroke: an integrated view. TINS 22(9):391–397PubMed Dirnagl U, Iadecola C, Moskowitz M (1999) Pathobiology of ischemic stroke: an integrated view. TINS 22(9):391–397PubMed
15.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Limburg M, Hijdra A (1990) Flunarizine in acute ischemic stroke: a pilot study. Eur Neurol 30(3):121–122PubMed Limburg M, Hijdra A (1990) Flunarizine in acute ischemic stroke: a pilot study. Eur Neurol 30(3):121–122PubMed
18.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Mulley G, Wilcox RG, Mitchell JR (1978) Dexamethasone in acute stroke. Br Med J 2(6143):994–996PubMed Mulley G, Wilcox RG, Mitchell JR (1978) Dexamethasone in acute stroke. Br Med J 2(6143):994–996PubMed
22.
Zurück zum Zitat 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 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.
Zurück zum Zitat Hu23F2G. 23F2G, LeukArrest. Drugs R D. 1999;1(1):25–26 Hu23F2G. 23F2G, LeukArrest. Drugs R D. 1999;1(1):25–26
24.
Zurück zum Zitat 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 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.
Zurück zum Zitat Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568PubMed Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568PubMed
26.
Zurück zum Zitat Obrenovitch TP (2008) Molecular physiology of preconditioning-induced brain tolerance to ischemia. Physiol Rev 88(1):211–247PubMed Obrenovitch TP (2008) Molecular physiology of preconditioning-induced brain tolerance to ischemia. Physiol Rev 88(1):211–247PubMed
27.
Zurück zum Zitat 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 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.
Zurück zum Zitat Streit WJ, Mrak RE, Griffin WS (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation 1(1):14PubMed Streit WJ, Mrak RE, Griffin WS (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation 1(1):14PubMed
29.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Garden GA, Moller T (2006) Microglia biology in health and disease. J Neuroimmune Pharmacol 1(2):127–137PubMed Garden GA, Moller T (2006) Microglia biology in health and disease. J Neuroimmune Pharmacol 1(2):127–137PubMed
37.
Zurück zum Zitat Gibson CL, Coughlan TC, Murphy SP (2005) Glial nitric oxide and ischemia. Glia 50(4):417–426PubMed Gibson CL, Coughlan TC, Murphy SP (2005) Glial nitric oxide and ischemia. Glia 50(4):417–426PubMed
38.
Zurück zum Zitat Allan SM, Rothwell NJ (2001) Cytokines and acute neurodegeneration. Nat Rev Neurosci 2(10):734–744PubMed Allan SM, Rothwell NJ (2001) Cytokines and acute neurodegeneration. Nat Rev Neurosci 2(10):734–744PubMed
39.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Zheng Z, Yenari MA (2004) Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol Res 26(8):884–892PubMed Zheng Z, Yenari MA (2004) Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol Res 26(8):884–892PubMed
45.
Zurück zum Zitat 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 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.
Zurück zum Zitat Chrousos GP (1995) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 332(20):1351–1362PubMed Chrousos GP (1995) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 332(20):1351–1362PubMed
47.
Zurück zum Zitat 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 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.
Zurück zum Zitat Saper CB, Loewy AD, Swanson LW, Cowan WM (1976) Direct hypothalamo-autonomic connections. Brain Res 117(2):305–312PubMed Saper CB, Loewy AD, Swanson LW, Cowan WM (1976) Direct hypothalamo-autonomic connections. Brain Res 117(2):305–312PubMed
49.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Yilmaz G, Arumugam TV, Stokes KY, Granger DN (2006) Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 113(17):2105–2112PubMed 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Kochanek PM, Hallenbeck JM (1992) Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23(9):1367–1379PubMed Kochanek PM, Hallenbeck JM (1992) Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23(9):1367–1379PubMed
70.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Lagasse E, Weissman IL (1994) bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages. J Exp Med 179(3):1047–1052PubMed 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Meszaros AJ, Reichner JS, Albina JE (1999) Macrophage phagocytosis of wound neutrophils. J Leukoc Biol 65(1):35–42PubMed Meszaros AJ, Reichner JS, Albina JE (1999) Macrophage phagocytosis of wound neutrophils. J Leukoc Biol 65(1):35–42PubMed
79.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Stoll G, Jander S, Schroeter M (1998) Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56:149–171PubMed Stoll G, Jander S, Schroeter M (1998) Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56:149–171PubMed
87.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Marler JR, Goldstein LB (2003) Medicine. Stroke—tPA and the clinic. Science 301(5640):1677PubMed Marler JR, Goldstein LB (2003) Medicine. Stroke—tPA and the clinic. Science 301(5640):1677PubMed
97.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Ende N, Chen R (2002) Parkinson's disease mice and human umbilical cord blood. J Med 33(1–4):173–180PubMed Ende N, Chen R (2002) Parkinson's disease mice and human umbilical cord blood. J Med 33(1–4):173–180PubMed
106.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Hayashi T, Su T (2001) Regulating ankyrin dynamics: roles of sigma-1 receptors. Proc Natl Acad Sci USA 98(2):491–496PubMed Hayashi T, Su T (2001) Regulating ankyrin dynamics: roles of sigma-1 receptors. Proc Natl Acad Sci USA 98(2):491–496PubMed
111.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Xiong ZG, Chu XP, Simon RP (2007) Acid sensing ion channels—novel therapeutic targets for ischemic brain injury. Front Biosci 12:1376–1386PubMed Xiong ZG, Chu XP, Simon RP (2007) Acid sensing ion channels—novel therapeutic targets for ischemic brain injury. Front Biosci 12:1376–1386PubMed
126.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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
Metadaten
Titel
Implications of Immune System in Stroke for Novel Therapeutic Approaches
verfasst von
Aaron A. Hall
Keith R. Pennypacker
Publikationsdatum
01.06.2010
Verlag
Springer-Verlag
Erschienen in
Translational Stroke Research / Ausgabe 2/2010
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-009-0003-y

Weitere Artikel der Ausgabe 2/2010

Translational Stroke Research 2/2010 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Schwindelursache: Massagepistole lässt Otholiten tanzen

14.05.2024 Benigner Lagerungsschwindel Nachrichten

Wenn jüngere Menschen über ständig rezidivierenden Lagerungsschwindel klagen, könnte eine Massagepistole der Auslöser sein. In JAMA Otolaryngology warnt ein Team vor der Anwendung hochpotenter Geräte im Bereich des Nackens.

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.