Breaking a Paradigm in Treatment of Acute Ischemic Stroke
Soo Jeong Shin, MD Kyoung Joo Cho, MS, Hyun-Woo Kim, BSc and Gyung Whan Kim, MD
Department of Neurology, Stroke and Neurocritical Care Section, Yonsei University College of Medicine,Brain Research Institute, Seoul, Korea
ABSTRACT
Stroke is the second leading cause of death in Korea and responsible for serious long-term disability. Although rt-PA is an approved drug, only 1-3% of stroke patients are receiving the treatment because of its limited 3 hour time window. In this review, we will overview the basic molecular mechanism of acute ischemic stroke and current stroke treatment then discuss about current issue in Korea. Basic concept of stroke treatment is focused on saving the ischemic penumbra; area that is at risk of cell death but potentially salvageable. Apoptosis are believed to play critical roles in ischemic damage, especially in the penumbral zone. Apoptosis is an active form of cell death as a strategy to preserve genomic stability from DNA damage. If DNA damage is overwhelming the capacity of DNA repair, cells that harbor DNA damage are removed from the population by death. Execution of apoptosis is preceded rapidly by activation of complex signal pathways like caspase-dependent and caspase-independent pathways. By ‘turning off’ the death signal which is activated by massive DNA damage, initiation of apoptosis can be stopped and this concept can be a new therapeutic target of acute ischemic stroke. Reperfusion therapy and neuroprotective agent are two main streams for treatment of acute ischemic stroke. Although, many clinical trials have been done, rt-PA is the only FDA approved medical therapy for patients who can be treated within 3 hours of stroke onset. Emerging endovascular mechanical reperfusion device (clot retrieval device or MERCI) is approved by FDA and its results of recent clinical trials are promising. Neuroprotective agents were successful in animal models of ischemia, they have been unsuccessful in human trials. Clinical trials of NXY-059, one of promising neuroprotective agents, fail to widen the therapeutic window. So far, treatments of acute ischemic stroke have been based on epidemiological approach, not molecular pathophysiology. Introduction of neurocritical care, which will provide more professional, true meaning of treatment, is urgent. And paradigm of treatment of acute ischemic stroke should be focused on repairing damaged neuron by ischemia, not preventing further damage by reperfusion or neuroprotective agent.
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