Progress of adjuvant treatment with tissue plasminogen activator beyond time window in ischemic stroke

WU Ye-jun CHEN Chun-hua*

doi:10.16098/j.issn.0529-1356.2019.06.028

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Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (6) : 850-856. DOI: 10.16098/j.issn.0529-1356.2019.06.028

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Progress of adjuvant treatment with tissue plasminogen activator beyond time window in ischemic stroke

WU Ye-jun CHEN Chun-hua*

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Abstract

Tissue plasminogen activator (tPA) thrombolysis remains the gold standard for the treatment of ischemic stroke. However, the time window of tPA treatment and the fatal side effects caused by application beyond the time window limit clinical application of tPA. In order to address the limitations, combined use of tPA with other drug or non-drug interventional approaches has been proposed and some combination therapies have been experimentally validated to decrease the complications beyond the time window, especially hemorrhagic transformation (HT). The mechanisms by which the combined drugs act include protecting the blood-brain barrier, enhancing angiogenesis, protecting cerebral blood vessels, etc. Non-drug interventions include stem cell transplantation and gas therapy with multiple biological effects. The combination of tPA and the above treatments intends to alleviate the side effects of delayed tPA treatment and the neurological deficits and behavioral impairment induced by stroke. Therefore, adjuvant therapy is an innovative form of treatment which addresses the limiting factors of tPA therapy and may prolong the time window of ischemic stroke.

Key words

Adjuvant therapy / Tissue plasminogen activator / Time window / Hemorrhagic transformation / Matrix metalloproteinase

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WU Ye-jun CHEN Chun-hua. Progress of adjuvant treatment with tissue plasminogen activator beyond time window in ischemic stroke[J]. Acta Anatomica Sinica. 2019, 50(6): 850-856 https://doi.org/10.16098/j.issn.0529-1356.2019.06.028

References

［1］ Feigin VL, Abajobir AA, Abate KH, et al. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 ［J］. Lancet Neurol, 2017, 16(11): 877-897.

［2］ Wang WZ, Jiang B, Sun H, et al. Prevalence, incidence, and mortality of stroke in china results from a nationwide population-based survey of 480 687 adults ［J］. Circulation, 2017, 135(8): 759-771.

［3］ Sidney S, Quesenberry CP, Jaffe MG, et al. Recent trends in cardiovascular mortality in the united states and public health goals ［J］. Jama Cardiol, 2016, 1(5): 594-599.

［4］ Suzuki Y. Role of tissue-type plasminogen activator in ischemic stroke ［J］. J Pharmacol Sci, 2010, 113(3): 203-207.

［5］ Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update a report from the american heart association ［J］. Circulation, 2018, 137(12): E67-E492.

［6］ Caruso P, Naccarato M, Furlanis G, et al. Wake-up stroke and CT perfusion: effectiveness and safety of reperfusion therapy ［J］. Neurol Sci, 2018, 39(10):1705-1712.

［7］ Pieraccini M, Guerrini S, Laiolo E, et al. Acute massive and submassive pulmonary embolism: preliminary validation of aspiration mechanical thrombectomy in patients with contraindications to thrombolysis ［J］. Cardiovasc Intervent Radiol, 2018, 41(12):1840-1848.

［8］ Mao YT, Mitchell P, Churilov L, et al. Early recanalization postintravenous thrombolysis in ischemic stroke with large vessel occlusion: a digital subtraction angiography study ［J］. CNS Neurosci Ther, 2016, 22(8): 643-647.

［9］ Lum C, Stys PK, Hogan MJ, et al. Acute anterior circulation stroke: recanalization using clot angioplasty ［J］. Can J Neurol Sci, 2006, 33(2): 217-222.

［10］ Tian C, Cao X, Wang J. Recanalisation therapy in patients with acute ischaemic stroke caused by large artery occlusion: choice of therapeutic strategy according to underlying aetiological mechanism ［J］? Stroke Vasc Neurol, 2017, 2(4): 244-250.

［11］ Jiang Z, Watts LT, Huang S, et al. The effects of methylene blue on autophagy and apoptosis in mri-defined normal tissue, ischemic penumbra and ischemic core ［J］. PLoS One, 2015, 10(6): e0131929.

［12］ Levi H, Schoknecht K, Prager O, et al. Stimulation of the sphenopalatine ganglion induces reperfusion and blood-brain barrier protection in the photothrombotic stroke model ［J］. PLoS One, 2012, 7(6): e39636.

［13］ Motyer R, Kok HK, Asadi H, et al. Outcomes of endovascular treatment for acute large-vessel ischaemic stroke more than 6 h after symptom onset ［J］. J Intern Med, 2017, 282(6): 537-545.

［14］ Motyer R, Thornton J, Power S, et al. Endovascular thrombectomy beyond 12 hours of stroke onset: a stroke network's experience of late intervention ［J］. J Neurointerv Surg, 2018, 10(11):1043-1046

［15］ Manning NW, Wenderoth J, Alsahli K, et al. Endovascular thrombectomy >24-hr from stroke symptom onset ［J］. Front Neurol, 2018, 9: 501.

［16］ Wang W, Li M, Chen Q, et al. Hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke: mechanisms, models, and biomarkers ［J］. Mol Neurobiol, 2015, 52(3): 1572-1579.

［17］ Yang Y, Salayandia VM, Thompson JF, et al. Attenuation of acute stroke injury in rat brain by minocycline promotes blood-brain barrier remodeling and alternative microglia/macrophage activation during recovery ［J］. J Neuroinflamm, 2015, 12:26.

［18］ Murata Y, Rosell A, Scannevin RH, et al. Extension of the thrombolytic time window with minocycline in experimental stroke ［J］. Stroke, 2008, 39(12): 3372-3377.

［19］ Ishiguro M, Mishiro K, Fujiwara Y, et al. Phosphodiesterase-Ⅲ inhibitor prevents hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tPA ［J］. PLoS One, 2010, 5(12): e15178.

［20］ Fukuoka T, Hayashi T, Hirayama M, et al. Cilostazol inhibits platelet-endothelial cell interaction in murine microvessels after transient bilateral common carotid artery occlusion ［J］. J Stroke Cerebrovasc, 2014, 23(5): 1056-1061.

［21］ Mishiro K, Ishiguro M, Suzuki Y, et al. A broad-spectrum matrix metalloproteinase inhibitor prevents hemorrhagic complications induced by tissue plasminogen activator in mice ［J］. Neuroscience, 2012, 205: 39-48.

［22］ Mayne M, Ni W, Yan HJ, et al. Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage ［J］. Stroke, 2001, 32(1): 240-247.

［23］ Fukuta T, Asai T, Sato A, et al. Neuroprotection against cerebral ischemia/reperfusion injury by intravenous administration of liposomal fasudil ［J］. Int J Pharm, 2016, 506(12): 129-137.

［24］ Ishiguro M, Kawasaki K, Suzuki Y, et al. A Rho kinase (ROCK) inhibitor, fasudil, prevents matrix metalloproteinase-9-related hemorrhagic transformation in mice treated with tissue plasminogen activator ［J］. Neuroscience, 2012, 220: 302-312.

［25］ So GH, Nakagawa S, Morofuji Y, et al. Candesartan improves ischemia-induced impairment of the blood-brain barrier in vitro ［J］. Cell Mol Neurobiol, 2015, 35(4): 563-572.

［26］ Ishrat T, Pillai B, Ergul A, et al. Candesartan reduces the hemorrhage associated with delayed tissue plasminogen activator treatment in rat embolic stroke ［J］. Neurochem Res, 2013, 38(12): 2668-2677.

［27］ Tan ZJ, Turner RC, Leon RL, et al. Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke ［J］. Stroke, 2013, 44(12): 3490-349

［28］ Tan Z, Lucke-Wold BP, Logsdon AF, et al. Bryostatin extends tPA time window to 6 h following middle cerebral artery occlusion in aged female rats ［J］. Eur J Pharmacol, 2015, 764: 404-412.

［29］ Choi NY, Kim JY, Hwang M, et al. Atorvastatin rejuvenates neural stem cells injured by oxygenglucose deprivation and induces neuronal differentiation through activating the PI3K/Akt and ERK pathways ［J］. Mol Neurobiol, 2018, 56(4):2964-2977.

［30］ Yang J, Pan Y, Li XJ, et al. Atorvastatin attenuates cognitive deficits through Akt1/caspase-3 signaling pathway in ischemic stroke ［J］. Brain Res, 2015, 1629: 231-239.

［31］ Zhang L, Chopp M, Jia LF, et al. Atorvastatin extends the therapeutic window for tPA to 6 h after the onset of embolic stroke in rats ［J］. J Cerebr Blood F Met, 2009, 29(11): 1816-1824.

［32］ Sumii T, Lo EH. Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats ［J］. Stroke, 2002, 33(3): 831-836.

［33］ Su EJ, Fredriksson L, Geyer M, et al. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke ［J］. Nat Med, 2008, 14(7): 731-737.

［34］ Wahlgren N, Thoren M, Hojeberg B, et al. Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis ［J］. J Intern Med, 2017, 281(3): 273-283.

［35］ Thiyagarajan M, Fernandez JA, Lane SM, et al. Activated protein C promotes neovascularization and neurogenesis in postischemic brain via protease-activated receptor 1 ［J］. J Neurosci, 2008, 28(48): 12788-12797.

［36］ Zuo W, Chen J, Zhang S, et al. IMM-H004 prevents toxicity induced by delayed treatment of tPA in a rat model of focal cerebral ischemia involving PKA-and PI3K-dependent Akt activation ［J］. Eur J Neurosci, 2014, 39(12): 2107-2118.

［37］ Niu F, Song XY, Hu JF, et al. IMM-H004, A new coumarin derivative, improved focal cerebral ischemia via blood-brain barrier protection in rats ［J］. J Stroke Cerebrovasc, 2017, 26(10): 2065-2073.

［38］ Dela Pena IC, Yang S, Shen G, et al. Extension of tissue plasminogen activator treatment window by granulocyte-colony stimulating factor in a thromboembolic rat model of stroke ［J］. Int J Mol Sci, 2018, 19(6): 1635.

［39］ Dela Pena IC, Yoo A, Tajiri N, et al. Granulocyte colony-stimulating factor attenuates delayed tPA-induced hemorrhagic transformation in ischemic stroke rats by enhancing angiogenesis and vasculogenesis ［J］. J Cereb Blood Flow Metab, 2015, 35(2): 338-346.

［40］ Ullegaddi R, Powers HJ, Gariballa SE. Antioxidant supplementation with or without B-group vitamins after acute ischemic stroke: a randomized controlled trial ［J］. Jpen-Parenter Enter, 2006, 30(2): 108-114.

［41］ Allahtavakoli M, Amin F, Esmaeeli-Nadimi A, et al. Ascorbic acid reduces the adverse effects of delayed administration of tissue plasminogen activator in a rat stroke model ［J］. Basic Clin Pharmacol Toxicol, 2015, 117(5): 335-339.

［42］ Arthur MC, Brown A, Carlson K, et al. Dodecafluoropentane improves neurological function following anterior ischemic stroke ［J］. Mol Neurobiol, 2017, 54(6): 4764-4770.

［43］ Culp WC, Brown AT, Lowery JD, et al. Dodecafluoropentane emulsion extends window for tpa therapy in a rabbit stroke model ［J］. Mol Neurobiol, 2015, 52(2): 979-984.

［44］ Aleynik A, Gernavage KM, Mourad YSh, et al. Stem cell delivery of therapies for brain disorders ［J］. Clin Transl Med, 2014, 3: 24.

［45］ Huang L, Wong SN, Snyder EY, et al. Human neural stem cells rapidly ameliorate symptomatic inflammation in early-stage ischemic-reperfusion cerebral injury ［J］. Stem Cell Res Ther, 2014, 5(6): 129.

［46］ Eckert AD, Hamblin M, Lee JP. Neural stem cells reduce symptomatic inflammation and mortality in aged stroke mice following delayed tPA treatment ［J］. Faseb J, 2017,-31.

［47］ Evans MA, Lim R, Kim HA, et al. Acute or delayed systemic administration of human amnion epithelial cells improves outcomes in experimental stroke ［J］. Stroke, 2018, 49(3): 700-709.

［48］ Shi S, Qi Z, Ma Q, et al. Normobaric hyperoxia reduces blood occludin fragments in rats and patients with acute ischemic stroke ［J］. Stroke, 2017, 48(10): 2848-2854.

［49］ Liang J, Qi Z, Liu W, et al. Normobaric hyperoxia slows BBB damage and expands the therapeutic time window for PA treatment in cerebral schema ［J］. Stroke, 2015, 46(5): 1344-1351.

［50］ Hu Q, Manaenko A, Bian HT, et al. Hyperbaric oxygen reduces infarction volume and hemorrhagic transformation through ATP/NAD(+)/Sirt1 pathway in hyperglycemic middle cerebral artery occlusion rats ［J］. Stroke, 2017, 48(6): 1655-1664.

［51］ Bentley P, Ganesalingam J, Jones ALC, et al. Prediction of stroke thrombolysis outcome using CT brain machine learning ［J］. Neuroimage Clin, 2014, 4: 635-640.

［52］ Hacke W. A new dawn for imaging-based selection in the treatment of acute stroke ［J］. New Engl J Med, 2018, 378(1): 81-83.

［53］ Xiang X, Cao F. Time window and “tissue window”: two approaches to assist decision-making in strokes ［J］. J Neurol, 2019, 266(2): 283-288.

［54］ Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct ［J］. New Engl J Med, 2018, 378(1): 11-21.

［55］ Minnerup J, Wersching H, Teuber A, et al. Outcome After thrombectomy and intravenous thrombolysis in patients with acute ischemic stroke: a prospective observational study ［J］. Strok, 2016, 47(6): 1584-1592.

［56］ Won S, Lee JH, Wali B, et al. Progesterone attenuates hemorrhagic transformation after delayed tPA treatment in an experimental model of stroke in rats: involvement of the VEGF-MMP pathway ［J］. J Cereb Blood Flow Metab, 2014, 34(1): 72-80.

［57］ Amaro S, Laredo C, Renu A, et al. Uric Acid therapy prevents early ischemic stroke progression: a tertiary analysis of the urico-ictus trial (efficacy study of combined treatment with uric acid and r-tPA in acute ischemic stroke) ［J］. Stroke, 2016, 47(11): 2874-2876.

［58］ Whiteley WN, Emberson J, Lees KR, et al. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis ［J］. Lancet Neurol, 2016, 15(9): 925-933.