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Published in: Critical Care 1/2016

Open Access 01-12-2016 | Review

Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy

Authors: Cynthia Santos Samary, Paolo Pelosi, Pedro Leme Silva, Patricia Rieken Macedo Rocco

Published in: Critical Care | Issue 1/2016

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Abstract

Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection. Pneumonia and urinary tract infection are the most common complications occurring in patients after stroke. The mechanisms involved in lung-brain interactions are still unknown, but some studies have suggested that inhibition of the cholinergic anti-inflammatory pathway and release of glucocorticoids, catecholamines, and damage-associated molecular patterns (DAMPs) are among the pathophysiological mechanisms involved in communication from the ischemic brain to the lungs after stroke. This review describes the modifications in local and systemic immunity that occur after stroke, outlines mechanisms of stroke-induced immunosuppression and their role in pneumonia, and highlights potential therapeutic targets to reduce post-stroke complications. Despite significant advances towards a better understanding of the pathophysiology of ischemic stroke-induced immunosuppression and stroke-associated pneumonia (SAP) in recent years, many unanswered questions remain. The true incidence and outcomes of SAP, especially in intensive care unit settings, have yet to be determined, as has the full extent of stroke-induced immunosuppression and its clinical implications.
Literature
1.
go back to reference Seshadri S, Beiser A, Kelly-Hayes M, et al. The lifetime risk of stroke: estimates from the Framingham Study. Stroke. 2006;37(2):345–50.CrossRefPubMed Seshadri S, Beiser A, Kelly-Hayes M, et al. The lifetime risk of stroke: estimates from the Framingham Study. Stroke. 2006;37(2):345–50.CrossRefPubMed
2.
go back to reference Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol. 2007;6(2):182–7.CrossRefPubMed Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol. 2007;6(2):182–7.CrossRefPubMed
4.
go back to reference Chamorro A, Urra X, Planas AM. Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke. 2007;38(3):1097–103.CrossRefPubMed Chamorro A, Urra X, Planas AM. Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke. 2007;38(3):1097–103.CrossRefPubMed
6.
go back to reference Smith WS. Pathophysiology of focal cerebral ischemia: a therapeutic perspective. J Vasc Interv Radiol. 2004;15(1 Pt 2):S3–12.CrossRefPubMed Smith WS. Pathophysiology of focal cerebral ischemia: a therapeutic perspective. J Vasc Interv Radiol. 2004;15(1 Pt 2):S3–12.CrossRefPubMed
7.
go back to reference Lai TW, Zhang S, Wang YT. Excitotoxicity and stroke: identifying novel targets for neuroprotection. Prog Neurobiol. 2014;115:157–88.CrossRefPubMed Lai TW, Zhang S, Wang YT. Excitotoxicity and stroke: identifying novel targets for neuroprotection. Prog Neurobiol. 2014;115:157–88.CrossRefPubMed
8.
go back to reference Simon RP, Swan JH, Griffiths T, et al. Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science. 1984;226(4676):850–2.CrossRefPubMed Simon RP, Swan JH, Griffiths T, et al. Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science. 1984;226(4676):850–2.CrossRefPubMed
9.
go back to reference Yilmaz G, Granger DN. Leukocyte recruitment and ischemic brain injury. Neuromol Med. 2010;12(2):193–204.CrossRef Yilmaz G, Granger DN. Leukocyte recruitment and ischemic brain injury. Neuromol Med. 2010;12(2):193–204.CrossRef
10.
go back to reference Renu A, Amaro S, Laredo C, et al. Relevance of blood-brain barrier disruption after endovascular treatment of ischemic stroke: dual-energy computed tomographic study. Stroke. 2015;46(3):673–9.CrossRefPubMed Renu A, Amaro S, Laredo C, et al. Relevance of blood-brain barrier disruption after endovascular treatment of ischemic stroke: dual-energy computed tomographic study. Stroke. 2015;46(3):673–9.CrossRefPubMed
11.
go back to reference Gliem M, Mausberg AK, Lee JI, et al. Macrophages prevent hemorrhagic infarct transformation in murine stroke models. Ann Neurol. 2012;71(6):743–52.CrossRefPubMed Gliem M, Mausberg AK, Lee JI, et al. Macrophages prevent hemorrhagic infarct transformation in murine stroke models. Ann Neurol. 2012;71(6):743–52.CrossRefPubMed
12.
go back to reference Clausen BH, Lambertsen KL, Babcock AA, et al. 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.CrossRefPubMedPubMedCentral Clausen BH, Lambertsen KL, Babcock AA, et al. 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.CrossRefPubMedPubMedCentral
13.
go back to reference Buck BH, Liebeskind DS, Saver JL, et al. Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke. 2008;39(2):355–60.CrossRefPubMed Buck BH, Liebeskind DS, Saver JL, et al. Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke. 2008;39(2):355–60.CrossRefPubMed
14.
go back to reference Harris AK, Ergul A, Kozak A, et al. Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke. BMC Neurosci. 2005;6:49.CrossRefPubMedPubMedCentral Harris AK, Ergul A, Kozak A, et al. Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke. BMC Neurosci. 2005;6:49.CrossRefPubMedPubMedCentral
15.
go back to reference Cuartero MI, Ballesteros I, Moraga A, et al. N2 neutrophils, novel players in brain inflammation after stroke: modulation by the PPARgamma agonist rosiglitazone. Stroke. 2013;44(12):3498–508.CrossRefPubMed Cuartero MI, Ballesteros I, Moraga A, et al. N2 neutrophils, novel players in brain inflammation after stroke: modulation by the PPARgamma agonist rosiglitazone. Stroke. 2013;44(12):3498–508.CrossRefPubMed
16.
17.
go back to reference Kleinschnitz C, Kraft P, Dreykluft A, et al. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood. 2013;121(4):679–91.CrossRefPubMedPubMedCentral Kleinschnitz C, Kraft P, Dreykluft A, et al. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood. 2013;121(4):679–91.CrossRefPubMedPubMedCentral
18.
go back to reference Prass K, Meisel C, Hoflich C, et al. 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. 2003;198(5):725–36.CrossRefPubMedPubMedCentral Prass K, Meisel C, Hoflich C, et al. 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. 2003;198(5):725–36.CrossRefPubMedPubMedCentral
21.
go back to reference Meisel C, Schwab JM, Prass K, et al. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. 2005;6(10):775–86.CrossRefPubMed Meisel C, Schwab JM, Prass K, et al. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. 2005;6(10):775–86.CrossRefPubMed
22.
go back to reference Romer C, Engel O, Winek K, et al. Blocking stroke-induced immunodeficiency increases CNS antigen-specific autoreactivity but does not worsen functional outcome after experimental stroke. J Neurosci. 2015;35(20):7777–94.CrossRefPubMed Romer C, Engel O, Winek K, et al. Blocking stroke-induced immunodeficiency increases CNS antigen-specific autoreactivity but does not worsen functional outcome after experimental stroke. J Neurosci. 2015;35(20):7777–94.CrossRefPubMed
24.
go back to reference Denes A, Ferenczi S, Kovacs KJ. Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size. J Neuroinflammation. 2011;8:164.CrossRefPubMedPubMedCentral Denes A, Ferenczi S, Kovacs KJ. Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size. J Neuroinflammation. 2011;8:164.CrossRefPubMedPubMedCentral
25.
26.
go back to reference Haeusler KG, Schmidt WU, Fohring F, et al. Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans. Cerebrovasc Dis. 2008;25(1-2):50–8.CrossRefPubMed Haeusler KG, Schmidt WU, Fohring F, et al. Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans. Cerebrovasc Dis. 2008;25(1-2):50–8.CrossRefPubMed
27.
go back to reference Ruhnau J, Schulze K, Gaida B, et al. Stroke alters respiratory burst in neutrophils and monocytes. Stroke. 2014;45(3):794–800.CrossRefPubMed Ruhnau J, Schulze K, Gaida B, et al. Stroke alters respiratory burst in neutrophils and monocytes. Stroke. 2014;45(3):794–800.CrossRefPubMed
28.
go back to reference Vogelgesang A, Grunwald U, Langner S, et al. Analysis of lymphocyte subsets in patients with stroke and their influence on infection after stroke. Stroke. 2008;39(1):237–41.CrossRefPubMed Vogelgesang A, Grunwald U, Langner S, et al. Analysis of lymphocyte subsets in patients with stroke and their influence on infection after stroke. Stroke. 2008;39(1):237–41.CrossRefPubMed
29.
go back to reference Offner H, Subramanian S, Parker SM, et al. Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. J Immunol. 2006;176(11):6523–31.CrossRefPubMed Offner H, Subramanian S, Parker SM, et al. Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. J Immunol. 2006;176(11):6523–31.CrossRefPubMed
30.
go back to reference Chamorro A, Horcajada JP, Obach V, et al. The Early Systemic Prophylaxis of Infection After Stroke study: a randomized clinical trial. Stroke. 2005;36(7):1495–500.CrossRefPubMed Chamorro A, Horcajada JP, Obach V, et al. The Early Systemic Prophylaxis of Infection After Stroke study: a randomized clinical trial. Stroke. 2005;36(7):1495–500.CrossRefPubMed
31.
go back to reference Offner H, Subramanian S, Parker SM, et al. Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab. 2006;26(5):654–65.CrossRefPubMed Offner H, Subramanian S, Parker SM, et al. Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab. 2006;26(5):654–65.CrossRefPubMed
32.
go back to reference Klehmet J, Harms H, Richter M, et al. Stroke-induced immunodepression and post-stroke infections: lessons from the preventive antibacterial therapy in stroke trial. Neuroscience. 2009;158(3):1184–93.CrossRefPubMed Klehmet J, Harms H, Richter M, et al. Stroke-induced immunodepression and post-stroke infections: lessons from the preventive antibacterial therapy in stroke trial. Neuroscience. 2009;158(3):1184–93.CrossRefPubMed
33.
go back to reference Chamorro A, Amaro S, Vargas M, et al. Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke. J Neurol Neurosurg Psychiatry. 2006;77(11):1279–81.CrossRefPubMedPubMedCentral Chamorro A, Amaro S, Vargas M, et al. Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke. J Neurol Neurosurg Psychiatry. 2006;77(11):1279–81.CrossRefPubMedPubMedCentral
34.
go back to reference Wong CH, Jenne CN, Lee WY, et al. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science. 2011;334(6052):101–5.CrossRefPubMed Wong CH, Jenne CN, Lee WY, et al. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science. 2011;334(6052):101–5.CrossRefPubMed
35.
go back to reference Urra X, Cervera A, Obach V, et al. Monocytes are major players in the prognosis and risk of infection after acute stroke. Stroke. 2009;40(4):1262–8.CrossRefPubMed Urra X, Cervera A, Obach V, et al. Monocytes are major players in the prognosis and risk of infection after acute stroke. Stroke. 2009;40(4):1262–8.CrossRefPubMed
36.
go back to reference Liesz A, Ruger H, Purrucker J, et al. Stress mediators and immune dysfunction in patients with acute cerebrovascular diseases. PloS One. 2013;8(9), e74839.CrossRefPubMedPubMedCentral Liesz A, Ruger H, Purrucker J, et al. Stress mediators and immune dysfunction in patients with acute cerebrovascular diseases. PloS One. 2013;8(9), e74839.CrossRefPubMedPubMedCentral
37.
go back to reference Abraham E, Arcaroli J, Shenkar R. Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia. J Immunol. 2001;166(1):522–30.CrossRefPubMed Abraham E, Arcaroli J, Shenkar R. Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia. J Immunol. 2001;166(1):522–30.CrossRefPubMed
38.
go back to reference Yang M, Zhang H, Voyno-Yasenetskaya T, et al. Requirement of Gbetagamma and c-Src in D2 dopamine receptor-mediated nuclear factor-kappaB activation. Mol Pharmacol. 2003;64(2):447–55.CrossRefPubMed Yang M, Zhang H, Voyno-Yasenetskaya T, et al. Requirement of Gbetagamma and c-Src in D2 dopamine receptor-mediated nuclear factor-kappaB activation. Mol Pharmacol. 2003;64(2):447–55.CrossRefPubMed
39.
go back to reference Bergquist J, Ohlsson B, Tarkowski A. Nuclear factor-kappa B is involved in the catecholaminergic suppression of immunocompetent cells. Ann NY Acad Sci. 2000;917:281–9.CrossRefPubMed Bergquist J, Ohlsson B, Tarkowski A. Nuclear factor-kappa B is involved in the catecholaminergic suppression of immunocompetent cells. Ann NY Acad Sci. 2000;917:281–9.CrossRefPubMed
40.
go back to reference Tung A, Herrera S, Fornal CA, et al. The effect of prolonged anesthesia with isoflurane, propofol, dexmedetomidine, or ketamine on neural cell proliferation in the adult rat. Anesth Analg. 2008;106(6):1772–7.CrossRefPubMed Tung A, Herrera S, Fornal CA, et al. The effect of prolonged anesthesia with isoflurane, propofol, dexmedetomidine, or ketamine on neural cell proliferation in the adult rat. Anesth Analg. 2008;106(6):1772–7.CrossRefPubMed
41.
go back to reference Haddad JJ, Saade NE, Safieh-Garabedian B. Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis. J Neuroimmunol. 2002;133(1-2):1–19.CrossRefPubMed Haddad JJ, Saade NE, Safieh-Garabedian B. Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis. J Neuroimmunol. 2002;133(1-2):1–19.CrossRefPubMed
42.
go back to reference Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med. 1995;332(20):1351–62.CrossRefPubMed Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med. 1995;332(20):1351–62.CrossRefPubMed
43.
go back to reference Emsley HC, Smith CJ, Gavin CM, et al. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J Neuroimmunol. 2003;139(1-2):93–101.CrossRefPubMed Emsley HC, Smith CJ, Gavin CM, et al. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J Neuroimmunol. 2003;139(1-2):93–101.CrossRefPubMed
44.
go back to reference Marklund N, Peltonen M, Nilsson TK, et al. Low and high circulating cortisol levels predict mortality and cognitive dysfunction early after stroke. J Int Med. 2004;256(1):15–21.CrossRef Marklund N, Peltonen M, Nilsson TK, et al. Low and high circulating cortisol levels predict mortality and cognitive dysfunction early after stroke. J Int Med. 2004;256(1):15–21.CrossRef
48.
go back to reference Ottani A, Giuliani D, Mioni C, et al. Vagus nerve mediates the protective effects of melanocortins against cerebral and systemic damage after ischemic stroke. J Cereb Blood Flow Metab. 2009;29(3):512–23.CrossRefPubMed Ottani A, Giuliani D, Mioni C, et al. Vagus nerve mediates the protective effects of melanocortins against cerebral and systemic damage after ischemic stroke. J Cereb Blood Flow Metab. 2009;29(3):512–23.CrossRefPubMed
49.
go back to reference Maouche K, Polette M, Jolly T, et al. {alpha}7 nicotinic acetylcholine receptor regulates airway epithelium differentiation by controlling basal cell proliferation. Am J Pathol. 2009;175(5):1868–82.CrossRefPubMedPubMedCentral Maouche K, Polette M, Jolly T, et al. {alpha}7 nicotinic acetylcholine receptor regulates airway epithelium differentiation by controlling basal cell proliferation. Am J Pathol. 2009;175(5):1868–82.CrossRefPubMedPubMedCentral
50.
go back to reference dos Santos CC, Shan Y, Akram A, et al. Neuroimmune regulation of ventilator-induced lung injury. Am J Respir Crit Care Med. 2011;183(4):471–82.CrossRefPubMed dos Santos CC, Shan Y, Akram A, et al. Neuroimmune regulation of ventilator-induced lung injury. Am J Respir Crit Care Med. 2011;183(4):471–82.CrossRefPubMed
51.
go back to reference Rosas-Ballina M, Tracey KJ. Cholinergic control of inflammation. J Int Med. 2009;265(6):663–79.CrossRef Rosas-Ballina M, Tracey KJ. Cholinergic control of inflammation. J Int Med. 2009;265(6):663–79.CrossRef
52.
go back to reference Walter U, Knoblich R, Steinhagen V, et al. Predictors of pneumonia in acute stroke patients admitted to a neurological intensive care unit. J Neurol. 2007;254(10):1323–9.CrossRefPubMed Walter U, Knoblich R, Steinhagen V, et al. Predictors of pneumonia in acute stroke patients admitted to a neurological intensive care unit. J Neurol. 2007;254(10):1323–9.CrossRefPubMed
53.
54.
go back to reference Villarreal A, Aviles Reyes RX, Angelo MF, et al. S100B alters neuronal survival and dendrite extension via RAGE-mediated NF-kappaB signaling. J Neurochem. 2011;117(2):321–32.CrossRefPubMed Villarreal A, Aviles Reyes RX, Angelo MF, et al. S100B alters neuronal survival and dendrite extension via RAGE-mediated NF-kappaB signaling. J Neurochem. 2011;117(2):321–32.CrossRefPubMed
55.
go back to reference Johnston KC, Li JY, Lyden PD, et al. Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators. Stroke. 1998;29(2):447–53.CrossRefPubMed Johnston KC, Li JY, Lyden PD, et al. Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators. Stroke. 1998;29(2):447–53.CrossRefPubMed
56.
go back to reference Teramoto S. Novel preventive and therapuetic strategy for post-stroke pneumonia. Expert Rev Neurother. 2009;9(8):1187–200.CrossRefPubMed Teramoto S. Novel preventive and therapuetic strategy for post-stroke pneumonia. Expert Rev Neurother. 2009;9(8):1187–200.CrossRefPubMed
57.
go back to reference Huang JY, Zhang DY, Yao Y, et al. Training in swallowing prevents aspiration pneumonia in stroke patients with dysphagia. J Int Med Res. 2006;34(3):303–6.CrossRefPubMed Huang JY, Zhang DY, Yao Y, et al. Training in swallowing prevents aspiration pneumonia in stroke patients with dysphagia. J Int Med Res. 2006;34(3):303–6.CrossRefPubMed
58.
go back to reference Arai T, Yoshimi N, Fujiwara H, et al. Serum substance P concentrations and silent aspiration in elderly patients with stroke. Neurology. 2003;61(11):1625–6.CrossRefPubMed Arai T, Yoshimi N, Fujiwara H, et al. Serum substance P concentrations and silent aspiration in elderly patients with stroke. Neurology. 2003;61(11):1625–6.CrossRefPubMed
59.
go back to reference Jia YX, Sekizawa K, Ohrui T, et al. Dopamine D1 receptor antagonist inhibits swallowing reflex in guinea pigs. Am J Physiol. 1998;274(1 Pt 2):R76–80.PubMed Jia YX, Sekizawa K, Ohrui T, et al. Dopamine D1 receptor antagonist inhibits swallowing reflex in guinea pigs. Am J Physiol. 1998;274(1 Pt 2):R76–80.PubMed
60.
go back to reference Harms H, Prass K, Meisel C, et al. Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PloS One. 2008;3(5), e2158.CrossRefPubMedPubMedCentral Harms H, Prass K, Meisel C, et al. Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PloS One. 2008;3(5), e2158.CrossRefPubMedPubMedCentral
61.
go back to reference Millns B, Gosney M, Jack CI, et al. Acute stroke predisposes to oral gram-negative bacilli–a cause of aspiration pneumonia? Gerontology. 2003;49(3):173–6.CrossRefPubMed Millns B, Gosney M, Jack CI, et al. Acute stroke predisposes to oral gram-negative bacilli–a cause of aspiration pneumonia? Gerontology. 2003;49(3):173–6.CrossRefPubMed
62.
go back to reference Yan L, Qing Y, Xingyi J, et al. Etiologic diagnosis and clinical treatment of multiple drug-resistant bacteria infection in elderly patients with stroke-associated pneumonia after neurosurgery. Cell Biochem Biophys. 2015;71(2):731–4.CrossRefPubMed Yan L, Qing Y, Xingyi J, et al. Etiologic diagnosis and clinical treatment of multiple drug-resistant bacteria infection in elderly patients with stroke-associated pneumonia after neurosurgery. Cell Biochem Biophys. 2015;71(2):731–4.CrossRefPubMed
63.
go back to reference Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009;40(8):2945–8.CrossRefPubMedPubMedCentral Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009;40(8):2945–8.CrossRefPubMedPubMedCentral
65.
go back to reference Giraldi-Guimardes A, Rezende-Lima M, Bruno FP, et al. Treatment with bone marrow mononuclear cells induces functional recovery and decreases neurodegeneration after sensorimotor cortical ischemia in rats. Brain Res. 2009;1266:108–20.CrossRefPubMed Giraldi-Guimardes A, Rezende-Lima M, Bruno FP, et al. Treatment with bone marrow mononuclear cells induces functional recovery and decreases neurodegeneration after sensorimotor cortical ischemia in rats. Brain Res. 2009;1266:108–20.CrossRefPubMed
66.
go back to reference Chen L, Zhang G, Khan AA, et al. Clinical efficacy and meta-analysis of stem cell therapies for patients with brain ischemia. Stem Cells Int. 2016;2016:6129579.PubMedPubMedCentral Chen L, Zhang G, Khan AA, et al. Clinical efficacy and meta-analysis of stem cell therapies for patients with brain ischemia. Stem Cells Int. 2016;2016:6129579.PubMedPubMedCentral
67.
go back to reference Dziedzic T, Slowik A, Pera J, et al. Beta-blockers reduce the risk of early death in ischemic stroke. J Neurol Sci. 2007;252(1):53–6.CrossRefPubMed Dziedzic T, Slowik A, Pera J, et al. Beta-blockers reduce the risk of early death in ischemic stroke. J Neurol Sci. 2007;252(1):53–6.CrossRefPubMed
68.
go back to reference Maier IL, Karch A, Mikolajczyk R, et al. Effect of beta-blocker therapy on the risk of infections and death after acute stroke–a historical cohort study. PloS One. 2015;10(2), e0116836.CrossRefPubMedPubMedCentral Maier IL, Karch A, Mikolajczyk R, et al. Effect of beta-blocker therapy on the risk of infections and death after acute stroke–a historical cohort study. PloS One. 2015;10(2), e0116836.CrossRefPubMedPubMedCentral
69.
go back to reference Yan GM, Ni B, Weller M, et al. Depolarization or glutamate receptor activation blocks apoptotic cell death of cultured cerebellar granule neurons. Brain Res. 1994;656(1):43–51.CrossRefPubMed Yan GM, Ni B, Weller M, et al. Depolarization or glutamate receptor activation blocks apoptotic cell death of cultured cerebellar granule neurons. Brain Res. 1994;656(1):43–51.CrossRefPubMed
70.
go back to reference Diener HC, AlKhedr A, Busse O, et al. Treatment of acute ischaemic stroke with the low-affinity, use-dependent NMDA antagonist AR-R15896AR. A safety and tolerability study. J Neurol. 2002;249(5):561–8.CrossRefPubMed Diener HC, AlKhedr A, Busse O, et al. Treatment of acute ischaemic stroke with the low-affinity, use-dependent NMDA antagonist AR-R15896AR. A safety and tolerability study. J Neurol. 2002;249(5):561–8.CrossRefPubMed
Metadata
Title
Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy
Authors
Cynthia Santos Samary
Paolo Pelosi
Pedro Leme Silva
Patricia Rieken Macedo Rocco
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1573-1

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