References
Arumugam TV, Granger DN, Mattson MP (2005) Stroke and T-cells. NeuroMolecular Med 7:229–242. https://doi.org/10.1385/NMM:7:3:229
Bang OY et al (2007) Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. Neurology 68:737–742. https://doi.org/10.1212/01.wnl.0000252799.64165.d5
Bodhankar S, Chen Y, Vandenbark AA, Murphy SJ, Offner H (2013) IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke. Metab Brain Dis 28:375–386. https://doi.org/10.1007/s11011-013-9413-3
Borregaard N, Cowland JB (1997) Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89:3503–3521
Buratti L, Cagnetti C, Balucani C, Viticchi G, Falsetti L, Luzzi S, Lattanzi S, Provinciali L, Silvestrini M (2014) Blood pressure variability and stroke outcome in patients with internal carotid artery occlusion. J Neurol Sci 339:164–168. https://doi.org/10.1016/j.jns.2014.02.007
Coull BM, Williams LS, Goldstein LB, Meschia JF, Heitzman D, Chaturvedi S, Johnston KC, Starkman S, Morgenstern LB, Wilterdink JL, Levine SR, Saver JL, Joint Stroke Guideline Development Committee of the American Academy of Neurology, American Stroke Association (2002) Anticoagulants and antiplatelet agents in acute ischemic stroke: report of the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association (a division of the American Heart Association). Stroke 33:1934–1942
Cucchiara B et al (2009) Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke: pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II Trials. Stroke 40:3067–3072. https://doi.org/10.1161/STROKEAHA.109.554386
Di Napoli M, Slevin M, Popa-Wagner A, Singh P, Lattanzi S, Divani AA (2018) Monomeric C-reactive protein and cerebral hemorrhage: from bench to bedside. Front Immunol 9:1921. https://doi.org/10.3389/fimmu.2018.01921
Divani AA et al (2019) Blood pressure variability predicts poor in-hospital outcome in spontaneous intracerebral hemorrhage. Stroke 50:2023–2029. https://doi.org/10.1161/STROKEAHA.119.025514
Durukan A et al (2009) Post-ischemic blood-brain barrier leakage in rats: one-week follow-up by MRI. Brain Res 1280:158–165. https://doi.org/10.1016/j.brainres.2009.05.025
Frenkel D, Huang Z, Maron R, Koldzic DN, Moskowitz MA, Weiner HL (2005) Neuroprotection by IL-10-producing MOG CD4+ T cells following ischemic stroke. J Neurol Sci 233:125–132. https://doi.org/10.1016/j.jns.2005.03.022
Gibson PH et al (2010) Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 105:186–191. https://doi.org/10.1016/j.amjcard.2009.09.007
Gidday JM et al (2005) Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am J Physiol Heart Circ Physiol 289:H558–H568. https://doi.org/10.1152/ajpheart.01275.2004
Guo Y et al (2015) Lower serum calcium level is associated with hemorrhagic transformation after thrombolysis. Stroke 46:1359–1361. https://doi.org/10.1161/STROKEAHA.115.008992
Guo Z, Yu S, Xiao L, Chen X, Ye R, Zheng P, Dai Q, Sun W, Zhou C, Wang S, Zhu W, Liu X (2016) Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke. J Neuroinflammation 13:199. https://doi.org/10.1186/s12974-016-0680-x
Hamann GF, del Zoppo GJ, von Kummer R (1999) Hemorrhagic transformation of cerebral infarction--possible mechanisms. Thromb Haemost 82(Suppl 1):92–94
Hurn PD, Subramanian S, Parker SM, Afentoulis ME, Kaler LJ, Vandenbark AA, Offner H (2007) T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab : official journal of the International Society of Cerebral Blood Flow and Metabolism 27:1798–1805. https://doi.org/10.1038/sj.jcbfm.9600482
Jickling GC, Liu D, Stamova B, Ander BP, Zhan X, Lu A, Sharp FR (2014) Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab : official journal of the International Society of Cerebral Blood Flow and Metabolism 34:185–199. https://doi.org/10.1038/jcbfm.2013.203
Kidwell CS, Saver JL, Carneado J, Sayre J, Starkman S, Duckwiler G, Gobin YP, Jahan R, Vespa P, Villablanca JP, Liebeskind DS, Vinuela F (2002) Predictors of hemorrhagic transformation in patients receiving intra-arterial thrombolysis. Stroke 33:717–724
Komotar RJ et al (2008) The role of complement in stroke therapy. Adv Exp Med Biol 632:23–33
Larrue V, von Kummer RR, Muller A, Bluhmki E (2001) Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke 32:438–441. https://doi.org/10.1161/01.str.32.2.438
Lattanzi S, Bartolini M, Provinciali L, Silvestrini M (2016) Glycosylated hemoglobin and functional outcome after acute ischemic stroke. J Stroke Cerebrovasc Dis 25:1786–1791. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.03.018
Lattanzi S, Brigo F, Trinka E, Cagnetti C, Di Napoli M, Silvestrini M (2019) Neutrophil-to-lymphocyte ratio in acute cerebral hemorrhage: a system review. Transl Stroke Res 10:137–145. https://doi.org/10.1007/s12975-018-0649-4
Lattanzi S, Cagnetti C, Rinaldi C, Angelocola S, Provinciali L, Silvestrini M (2018) Neutrophil-to-lymphocyte ratio improves outcome prediction of acute intracerebral hemorrhage. J Neurol Sci 387:98–102. https://doi.org/10.1016/j.jns.2018.01.038
Lattanzi S, Di Napoli M, Ricci S, Divani AA (2020) Matrix Metalloproteinases in acute intracerebral hemorrhage. Neurotherapeutics. https://doi.org/10.1007/s13311-020-00839-0
Lattanzi S, Silvestrini M (2015) Optimal achieved blood pressure in acute intracerebral hemorrhage: INTERACT2. Neurology 85:557–558. https://doi.org/10.1212/01.wnl.0000470918.40985.d0
Lattanzi S, Silvestrini M, Provinciali L (2013) Elevated blood pressure in the acute phase of stroke and the role of angiotensin receptor blockers. Int J Hypertens 2013:941783. https://doi.org/10.1155/2013/941783
Lee JH et al (2010) Symptomatic hemorrhagic transformation and its predictors in acute ischemic stroke with atrial fibrillation. Eur Neurol 64:193–200. https://doi.org/10.1159/000319048
Li P et al (2014) Essential role of program death 1-ligand 1 in regulatory T-cell-afforded protection against blood-brain barrier damage after stroke. Stroke 45:857–864. https://doi.org/10.1161/STROKEAHA.113.004100
Liesz A et al (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15:192–199. https://doi.org/10.1038/nm.1927
Liu K, Yan S, Zhang S, Guo Y, Lou M (2016) Systolic blood pressure variability is associated with severe hemorrhagic transformation in the early stage after thrombolysis. Transl Stroke Res 7:186–191. https://doi.org/10.1007/s12975-016-0458-6
Motto C, Ciccone A, Aritzu E, Boccardi E, De Grandi C, Piana A, Candelise L (1999) Hemorrhage after an acute ischemic stroke. MAST-I Collaborative Group. Stroke 30:761–764
Petrault O, Ouk T, Gautier S, Laprais M, Gele P, Bastide M, Bordet R (2005) Pharmacological neutropenia prevents endothelial dysfunction but not smooth muscle functions impairment induced by middle cerebral artery occlusion. Br J Pharmacol 144:1051–1058. https://doi.org/10.1038/sj.bjp.0706124
Qun S et al (2017) Neutrophil-to-lymphocyte ratio predicts 3-month outcome of acute ischemic stroke. Neurotox Res 31:444–452. https://doi.org/10.1007/s12640-017-9707-z
Ren X, Akiyoshi K, Dziennis S, Vandenbark AA, Herson PS, Hurn PD, Offner H (2011) Regulatory B cells limit CNS inflammation and neurologic deficits in murine experimental stroke. J Neurosci 31:8556–8563. https://doi.org/10.1523/JNEUROSCI.1623-11.2011
Rosell A, Cuadrado E, Ortega-Aznar A, Hernandez-Guillamon M, Lo EH, Montaner J (2008) MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke 39:1121–1126. https://doi.org/10.1161/STROKEAHA.107.500868
Sandoval KE, Witt KA (2008) Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiol Dis 32:200–219. https://doi.org/10.1016/j.nbd.2008.08.005
Seiffge DJ et al (2019) Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation. Lancet Neurol 18:117–126. https://doi.org/10.1016/S1474-4422(18)30356-9
Stowe AM, Adair-Kirk TL, Gonzales ER, Perez RS, Shah AR, Park TS, Gidday JM (2009) Neutrophil elastase and neurovascular injury following focal stroke and reperfusion. Neurobiol Dis 35:82–90. https://doi.org/10.1016/j.nbd.2009.04.006
Tan S, Wang D, Liu M, Zhang S, Wu B, Liu B (2014) Frequency and predictors of spontaneous hemorrhagic transformation in ischemic stroke and its association with prognosis. J Neurol 261:905–912. https://doi.org/10.1007/s00415-014-7297-8
Wang W, Li M, Chen Q, Wang J (2015) Hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke: mechanisms, models, and biomarkers. Mol Neurobiol 52:1572–1579. https://doi.org/10.1007/s12035-014-8952-x
Yang C, Hawkins KE, Dore S, Candelario-Jalil E (2019) Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke. Am J Phys Cell Phys 316:C135–C153. https://doi.org/10.1152/ajpcell.00136.2018
Zahorec R (2001) Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 102:5–14
Zhang PL et al (2015) Analysis on the correlation factors for hemorrhagic transformation after intravenous thrombolytic therapy. Eur Rev Med Pharmacol Sci 19:1001–1008
Zhang W, Xiong Y, Yu L, Xiong A, Bao H, Cheng X (2019) Meta-analysis of stroke and bleeding risk in patients with various atrial fibrillation patterns receiving oral anticoagulants. Am J Cardiol 123:922–928. https://doi.org/10.1016/j.amjcard.2018.11.055
Acknowledgments
This work was supported by the grants from the National Key R&D Program of China (2017YFE0103700) and the National Science Foundation of China (81120108011 and 81771454), and the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.
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Sun, J., Meng, D., Liu, Z. et al. Neutrophil to Lymphocyte Ratio Is a Therapeutic Biomarker for Spontaneous Hemorrhagic Transformation. Neurotox Res 38, 219–227 (2020). https://doi.org/10.1007/s12640-020-00181-5
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DOI: https://doi.org/10.1007/s12640-020-00181-5