Neuroprotective effects of adjunctive treatments for acute stroke thrombolysis: a review of clinical evidence

References

• Yarbrough CK, Ong CJ, Beyer AB, et al. Endovascular thrombectomy for anterior circulation stroke: systematic review and meta-analysis. Stroke 2015;46:3177–83.
   PubMed Web of Science ®Google Scholar
• Powers WJ, Derdeyn CP, Biller J, et al. American Heart Association Stroke C. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015;46:3020–35.
   PubMed Web of Science ®Google Scholar
• Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 2012;379:2364–72.
   PubMed Web of Science ®Google Scholar
• Chamorro A, Dirnagl U, Urra X, et al. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurol 2016;15:869–81.
   PubMed Web of Science ®Google Scholar
• Wiendl H, Elger C, Forstl H, et al. Gaps between aims and achievements in therapeutic modification of neuronal damage ("neuroprotection"). Neurotherapeutics 2015;12:449–54.
   PubMed Web of Science ®Google Scholar
• Romanos E, Planas AM, Amaro S, et al. Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke. J Cerebral Blood Flow Metabolism 2007;27:14–20.
   PubMed Web of Science ®Google Scholar
• Hasegawa Y, Suzuki H, Sozen T, et al. Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke 2010;41:368–74.
   PubMed Web of Science ®Google Scholar
• Machado LS, Sazonova IY, Kozak A, et al. Minocycline and tissue-type plasminogen activator for stroke: assessment of interaction potential. Stroke 2009;40:3028–33.
   PubMed Web of Science ®Google Scholar
• Hoda MN, Siddiqui S, Herberg S, et al. Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. Stroke 2012;43:2794–9.
   PubMed Web of Science ®Google Scholar
• Tang XN, Liu L, Koike MA, et al. Mild hypothermia reduces tissue plasminogen activator-related hemorrhage and blood brain barrier disruption after experimental stroke. Therapeutic Hypothermia Temp Manag 2013;3:74–83.
   PubMed Web of Science ®Google Scholar
• Minnerup J, Wersching H, Schilling M, et al. Analysis of early phase and subsequent phase III stroke studies of neuroprotectants: outcomes and predictors for success. Exp Transl Stroke Med 2014;6:2.
   PubMedGoogle Scholar
• Bai J, Lyden PD. Revisiting cerebral postischemic reperfusion injury: new insights in understanding reperfusion failure, hemorrhage, and edema. Int J Stroke 2015;10:143–52.
   PubMed Web of Science ®Google Scholar
• Gursoy-Ozdemir Y, Can A, Dalkara T. Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia. Stroke 2004;35:1449–53.
   PubMed Web of Science ®Google Scholar
• Higgins J, Green S. Cochrane handbook for systematic reviews of interventions. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol 2011;2011:S38.
   Google Scholar
• Li R, Huang C, Chen J, et al. The role of uric acid as a potential neuroprotectant in acute ischemic stroke: a review of literature. Neurol Sci 2015;36:1097–103.
   PubMed Web of Science ®Google Scholar
• Wang Z, Lin Y, Liu Y, Chen Y, Wang B, Li C, Yan S, Wang Y, Zhao W. Serum uric acid levels and outcomes after acute ischemic stroke. Mol Neurobiol 2016;53:1753–9.
   PubMed Web of Science ®Google Scholar
• Amaro S, Urra X, Gomez-Choco M, et al. Uric acid levels are relevant in patients with stroke treated with thrombolysis. Stroke 2011;42:S28–32.
   PubMed Web of Science ®Google Scholar
• Liu X, Liu M, Chen M, et al. Serum uric acid is neuroprotective in Chinese patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator. J Stroke Cerebrovascular Dis 2015;24:1080–6. Epub 2015/03/31.
   PubMed Web of Science ®Google Scholar
• Llull L, Amaro S, Chamorro A. Administration of uric acid in the emergency treatment of acute ischemic stroke. Curr Neurol Neurosci Rep 2016;16:4.
   PubMed Web of Science ®Google Scholar
• Waring WS, Convery A, Mishra V, et al. Uric acid reduces exercise-induced oxidative stress in healthy adults. Clin Sci 2003;105:425–30.
   PubMed Web of Science ®Google Scholar
• Waring WS, Webb DJ, Maxwell SR. Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol 2001;38:365–71.
   PubMed Web of Science ®Google Scholar
• Amaro S, Llull L, Renu A, et al. Uric acid improves glucose-driven oxidative stress in human ischemic stroke. Ann Neurol 2015;77:775–83.
   PubMed Web of Science ®Google Scholar
• Amaro S, Soy D, Obach V, et al. A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke. Stroke 2007;38:2173–5. Epub 2007/05/26.
   PubMed Web of Science ®Google Scholar
• Chamorro A, Amaro S, Castellanos M, et al. Investigators U-I. Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial. Lancet Neurol 2014;13:453–60.
   PubMed Web of Science ®Google Scholar
• Llull L, Laredo C, Renu A, et al. Uric acid therapy improves clinical outcome in women with acute ischemic stroke. Stroke 2015;46:2162–7.
   PubMed Web of Science ®Google Scholar
• Massberg S, von Andrian UH. Fingolimod and sphingosine-1-phosphate–modifiers of lymphocyte migration. N Engl J Med 2006;355:1088–91.
   PubMed Web of Science ®Google Scholar
• Wei Y, Yemisci M, Kim HH, et al. Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol 2011;69:119–29.
   PubMed Web of Science ®Google Scholar
• Liu J, Zhang C, Tao W, et al. Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke. Int J Neurosci 2013;123:163–9.
   PubMed Web of Science ®Google Scholar
• Campos F, Qin T, Castillo J, et al. Fingolimod reduces hemorrhagic transformation associated with delayed tissue plasminogen activator treatment in a mouse thromboembolic model. Stroke 2013;44:505–11.
   PubMed Web of Science ®Google Scholar
• Fu Y, Zhang N, Ren L, et al. Impact of an immune modulator fingolimod on acute ischemic stroke. Proc Natl Acad Sci U S A 2014;111:18315–20. Epub 2014/12/10.
   PubMed Web of Science ®Google Scholar
• Zhu Z, Fu Y, Tian D, et al. Combination of the immune modulator fingolimod with alteplase in acute ischemic stroke: a pilot trial. Circulation 2015;132:1104–12. Epub 2015/07/24.
   PubMed Web of Science ®Google Scholar
• Koennecke HC, Belz W, Berfelde D, et al. Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit. Neurology 2011;77:965–72.
   PubMed Web of Science ®Google Scholar
• Finlayson O, Kapral M, Hall R, et al. Canadian Stroke N, Stroke Outcome Research Canada Working G. Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke. Neurology 2011;77:1338–45.
   PubMed Web of Science ®Google Scholar
• Mandala S, Hajdu R, Bergstrom J, et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 2002;296:346–9.
   PubMed Web of Science ®Google Scholar
• Kappos L, Cohen J, Collins W, et al. Fingolimod in relapsing multiple sclerosis: An integrated analysis of safety findings. Multiple Sclerosis Relat Disord 2014;3:494–504.
   PubMed Web of Science ®Google Scholar
• Chamorro A, Urra X, Planas AM. Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke 2007;38:1097–103.
   PubMed Web of Science ®Google Scholar
• 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;158:1184–93.
   PubMed Web of Science ®Google Scholar
• Lampl Y, Boaz M, Gilad R, et al. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology 2007;69:1404–10. Epub 2007/10/03.
   PubMed Web of Science ®Google Scholar
• Amiri-Nikpour MR, Nazarbaghi S, Hamdi-Holasou M, et al. An open-label evaluator-blinded clinical study of minocycline neuroprotection in ischemic stroke: gender-dependent effect. Acta Neurol Scand 2015;131:45–50. Epub 2014/08/27.
   PubMed Web of Science ®Google Scholar
• Yrjanheikki J, Tikka T, Keinanen R, et al. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A 1999;96:13496–500.
   PubMed Web of Science ®Google Scholar
• Fukuda S, Fini CA, Mabuchi T, et al. Focal cerebral ischemia induces active proteases that degrade microvascular matrix. Stroke 2004;35:998–1004.
   PubMed Web of Science ®Google Scholar
• Yang Y, Estrada EY, Thompson JF, et al. Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cerebral Blood Flow Metab 2007;27:697–709.
   PubMed Web of Science ®Google Scholar
• Inzitari D, Giusti B, Nencini P, et al. MMP9 variation after thrombolysis is associated with hemorrhagic transformation of lesion and death. Stroke 2013;44:2901–3.
   PubMed Web of Science ®Google Scholar
• Montaner J, Molina CA, Monasterio J, et al. Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 2003;107:598–603.
   PubMed Web of Science ®Google Scholar
• Bauer AT, Burgers HF, Rabie T, et al. Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement. J Cerebral Blood Flow Metab 2010;30:837–48.
   PubMed Web of Science ®Google Scholar
• Machado LS, Kozak A, Ergul A, et al. Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. BMC Neurosci 2006;7:56.
   PubMed Web of Science ®Google Scholar
• Murata Y, Rosell A, Scannevin RH, et al. Extension of the thrombolytic time window with minocycline in experimental stroke. Stroke 2008;39:3372–7.
   PubMed Web of Science ®Google Scholar
• Switzer JA, Hess DC, Ergul A, et al. Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke. Stroke 2011;42:2633–5. Epub 2011/07/09.
   PubMed Web of Science ®Google Scholar
• Fagan SC, Waller JL, Nichols FT, et al. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke 2010;41:2283–7.
   PubMed Web of Science ®Google Scholar
• Li J, McCullough LD. Sex differences in minocycline-induced neuroprotection after experimental stroke. J Cerebral Blood Flow Metab 2009;29:670–4.
   PubMed Web of Science ®Google Scholar
• Blacker DJ, Prentice D, Alvaro A, et al. Reducing haemorrhagic transformation after thrombolysis for stroke: a strategy utilising minocycline. Stroke Res Treatment 2013;2013:362961.
   PubMedGoogle Scholar
• Pan J, Li X, Peng Y. Remote ischemic conditioning for acute ischemic stroke: dawn in the darkness. Rev Neurosci 2016;27:501–10.
   PubMed Web of Science ®Google Scholar
• Dezfulian C, Garrett M, Gonzalez NR. Clinical application of preconditioning and postconditioning to achieve neuroprotection. Trans Stroke Res 2013;4:19–24.
   PubMed Web of Science ®Google Scholar
• Hoda MN, Bhatia K, Hafez SS, et al. Remote ischemic perconditioning is effective after embolic stroke in ovariectomized female mice. Trans Stroke Res 2014;5:484–90.
   PubMed Web of Science ®Google Scholar
• Liu X, Zhao S, Liu F, et al. Remote ischemic postconditioning alleviates cerebral ischemic injury by attenuating endoplasmic reticulum stress-mediated apoptosis. Trans Stroke Res 2014;5:692–700.
   PubMed Web of Science ®Google Scholar
• Cheng Z, Li L, Mo X, et al. Non-invasive remote limb ischemic postconditioning protects rats against focal cerebral ischemia by upregulating STAT3 and reducing apoptosis. Int J Mol Med 2014;34:957–66.
   PubMed Web of Science ®Google Scholar
• Botker HE, Kharbanda R, Schmidt MR, et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 2010;375:727–34.
   PubMed Web of Science ®Google Scholar
• Prunier F, Angoulvant D, Saint Etienne C, et al. The RIPOST-MI study, assessing remote ischemic perconditioning alone or in combination with local ischemic postconditioning in ST-segment elevation myocardial infarction. Basic Res Cardiol 2014;109:400.
   PubMed Web of Science ®Google Scholar
• Wegener S, Gottschalk B, Jovanovic V, et al. Stroke MRIiASSGotGCN. Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study. Stroke 2004;35:616–21.
   PubMed Web of Science ®Google Scholar
• Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology 2012;79:1853–61.
   PubMed Web of Science ®Google Scholar
• Meng R, Ding Y, Asmaro K, et al. Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment. Neurotherapeutics 2015;12:667–77.
   PubMed Web of Science ®Google Scholar
• Koch S, Katsnelson M, Dong C, et al. Remote ischemic limb preconditioning after subarachnoid hemorrhage: a phase Ib study of safety and feasibility. Stroke 2011;42:1387–91.
   PubMed Web of Science ®Google Scholar
• Hougaard KD, Hjort N, Zeidler D, et al. Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial. Stroke 2014;45:159–67. Epub 2013/11/10.
   PubMed Web of Science ®Google Scholar
• Warach S, Latour LL. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption. Stroke 2004;35:2659–61.
   PubMed Web of Science ®Google Scholar
• Aronowski J, Strong R, Grotta JC. Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cerebral Blood Flow Metab 1997;17:1048–56.
   PubMed Web of Science ®Google Scholar
• Pan J, Konstas AA, Bateman B, et al. Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology 2007;49:93–102.
   PubMed Web of Science ®Google Scholar
• Pico F, Rosso C, Meseguer E, et al. A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol. Int J Stroke 2016.
   PubMed Web of Science ®Google Scholar
• Lazzaro MA, Prabhakaran S. Induced hypothermia in acute ischemic stroke. Expert Opin Investig Drugs 2008;17:1161–74.
   PubMed Web of Science ®Google Scholar
• Hypothermia after Cardiac Arrest Study G. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–56.
   PubMed Web of Science ®Google Scholar
• Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63.
   PubMed Web of Science ®Google Scholar
• Dumitrascu OM, Lamb J, Lyden PD. Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke. Journal of Cerebral Blood Flow Metab 2016;36:1157–64. Epub 2016/04/20.
   PubMed Web of Science ®Google Scholar
• Bi M, Ma Q, Zhang S, Li J, et al. Local mild hypothermia with thrombolysis for acute ischemic stroke within a 6-h window. Clin Neurol Neurosurg 2011;113:768–73. Epub 2011/09/07.
   PubMed Web of Science ®Google Scholar
• Hemmen TM, Raman R, Guluma KZ, et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke 2010;41:2265–70. Epub 2010/08/21.
   PubMed Web of Science ®Google Scholar
• Wu TC, Grotta JC. Hypothermia for acute ischaemic stroke. Lancet Neurol 2013;12:275–84.
   PubMed Web of Science ®Google Scholar
• Han Z, Liu X, Luo Y, et al. Therapeutic hypothermia for stroke: Where to go? Exp Neurol 2015;272:67–77. Epub 2015/06/10.
   PubMed Web of Science ®Google Scholar
• Piironen K, Tiainen M, Mustanoja S, et al. Mild hypothermia after intravenous thrombolysis in patients with acute stroke: a randomized controlled trial. Stroke 2014;45:486–91.
   PubMed Web of Science ®Google Scholar
• Hong JM, Lee JS, Song HJ, et al. Therapeutic hypothermia after recanalization in patients with acute ischemic stroke. Stroke 2014;45:134–40. Epub 2013/11/10.
   PubMed Web of Science ®Google Scholar
• Chen J, Liu L, Zhang H, et al. Endovascular Hypothermia in Acute Ischemic Stroke: Pilot Study of Selective Intra-Arterial Cold Saline Infusion. Stroke 2016;47:1933–5.
   PubMed Web of Science ®Google Scholar
• Lapchak PA, Boitano PD. A novel method to promote behavioral improvement and enhance mitochondrial function following an embolic stroke. Brain Res 2016;1646:125–31.
   PubMed Web of Science ®Google Scholar
• Lapchak PA, De Taboada L. Transcranial near infrared laser treatment (NILT) increases cortical adenosine-5'-triphosphate (ATP) content following embolic strokes in rabbits. Brain Res 2010;1306:100–5.
   PubMed Web of Science ®Google Scholar
• Lapchak PA, Han MK, Salgado KF, et al. Safety profile of transcranial near-infrared laser therapy administered in combination with thrombolytic therapy to embolized rabbits. Stroke 2008;39:3073–8.
   PubMed Web of Science ®Google Scholar
• Lampl Y, Zivin JA, Fisher M, et al. Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1). Stroke 2007;38:1843–9.
   PubMed Web of Science ®Google Scholar
• Zivin JA, Albers GW, Bornstein N, et al. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke 2009;40:1359–64.
   PubMed Web of Science ®Google Scholar
• Meyer DM, Chen Y, Zivin JA. Dose-finding study of phototherapy on stroke outcome in a rabbit model of ischemic stroke. Neurosci Lett 2016;630:254–8.
   PubMed Web of Science ®Google Scholar
• del Zoppo GJ. Stroke and neurovascular protection. N Engl J Med 2006;354:553–5.
   PubMed Web of Science ®Google Scholar
• Saver JL, Starkman S, Eckstein M, et al. Coordinators. Prehospital use of magnesium sulfate as neuroprotection in acute stroke. N Engl J Med 2015;372:528–36.
   PubMed Web of Science ®Google Scholar
• Ji Z, Liu K, Cai L, et al. Therapeutic effect of tPA in ischemic stroke is enhanced by its combination with normobaric oxygen and hypothermia or ethanol. Brain Res 2015;1627:31–40. Epub 2015/09/01.
   PubMed Web of Science ®Google Scholar
• Cai L, Stevenson J, Geng X, et al. Combining Normobaric Oxygen with Ethanol or Hypothermia Prevents Brain Damage from Thromboembolic Stroke via PKC-Akt-NOX Modulation. Mol Neurobiol 2016. Epub 2016/03/12.
   Web of Science ®Google Scholar
• Lijnen HR. Plasmin and matrix metalloproteinases in vascular remodeling. Thromb Haemost 2001;86:324–33.
   PubMed Web of Science ®Google Scholar
• Cuadrado E, Ortega L, Hernandez-Guillamon M, et al. Tissue plasminogen activator (t-PA) promotes neutrophil degranulation and MMP-9 release. J Leukoc Biol 2008;84:207–14.
   PubMed Web of Science ®Google Scholar
• Sheth KN, Elm JJ, Molyneaux BJ, et al. Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2016;15:1160–9. Epub 2016/08/28.
   PubMed Web of Science ®Google Scholar
• Sheth KN, Kimberly WT, Elm JJ, et al. Exploratory analysis of glyburide as a novel therapy for preventing brain swelling. Neurocrit Care 2014;21:43–51. Epub 2014/03/29.
   PubMed Web of Science ®Google Scholar
• Simard JM, Sheth KN, Kimberly WT, et al. Glibenclamide in cerebral ischemia and stroke. Neurocrit Care 2014;20:319–33.
   PubMed Web of Science ®Google Scholar
• Pham L, O'Connor S, Yarbrough K, et al. Intravenous glyburide treatment is associated with reduced matrix metalloproteinase-9 in human acute stroke. Stroke 2013;73:2190–6.
   Google Scholar
• Lang W, Stadler CH, Poljakovic Z, et al. A prospective, randomized, placebo-controlled, double-blind trial about safety and efficacy of combined treatment with alteplase (rt-PA) and cerebrolysin in acute ischaemic hemispheric stroke. Int J Stroke 2013;8:95–104. Epub 2012/09/27.
   PubMed Web of Science ®Google Scholar
• Kimura K, Aoki J, Sakamoto Y, et al. Administration of edaravone, a free radical scavenger, during t-PA infusion can enhance early recanalization in acute stroke patients – a preliminary study. J Neurol Sci 2012;313:132–6. Epub 2011/10/05.
   PubMed Web of Science ®Google Scholar