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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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초록· 키워드
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Tissue plasminogen activator (tPA) is the only therapeutic agent approved to treat patients with acute ischemic stroke. The clinical benefits of tPA manifest when the agent is administered within 4.5 hours of stroke onset. However, tPA administration, especially delayed administration, is associated with increased intracranial hemorrhage (ICH), hemorrhagic transformation (HT), and mortality. In the ischemic brain, vascular remodeling factors are upregulated and microvascular structures are destabilized. These factors disrupt the blood brain barrier (BBB). Delayed recanalization of the vessels in the presence of relatively matured infarction appears to damage the BBB, resulting in HT or ICH, also known as reperfusion injury. Moreover, tPA itself activates matrix metalloproteases, further aggravating BBB disruption. Therefore, attenuation of edema, HT, or ICH after tPA treatment is an important therapeutic strategy that may enable clinicians to extend therapeutic time and increase the probability of excellent outcomes. Recently, numerous agents with various mechanisms have been developed to interfere with various steps of ischemia/ reperfusion injuries or BBB destabilization. These agents successfully reduce infarct volume and decrease the incidence of ICH and HT after delayed tPA treatment in various animal stroke models. However, only some have entered into clinical trials; the results have been intriguing yet unsatisfactory. In this narrative review, I describe such drugs and discuss the problems and future directions. These “tPA helpers” may be clinically used in the future to increase the efficacy of tPA in patients with acute ischemic stroke.
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참고문헌 (101)
참고문헌 신청
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group / 1995 / Tissue plasminogen activator for acute ischemic stroke / N Engl J Med 333:1581~1587
Hacke W / 2008 / Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke / N Engl J Med 359:1317~1329
Emberson J / 2014 / Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials / Lancet 384:1929~1935
Lees KR / 2016 / Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials / Stroke 47:2373~2379
Goyal M / 2016 / Endovascular thrombectomy after largevessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials / Lancet 387:1723~1731
Hacke W / 2008 / Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke / N Engl J Med 359:1317~1329
Emberson J / 2014 / Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials / Lancet 384:1929~1935
Lees KR / 2016 / Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials / Stroke 47:2373~2379
Goyal M / 2016 / Endovascular thrombectomy after largevessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials / Lancet 387:1723~1731
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