Enhancing Base Excision Repair of Mitochondrial DNA to Reduce Ischemic Injury Following Reperfusion
説明
<jats:title>Abstract</jats:title><jats:p>We hypothesize that enhancing mitochondrial base excision repair (BER) capability in brain will reduce reperfusion-associated ischemic brain injury. Post-stroke reperfusion was modeled in mice via transient filament occlusion of the middle cerebral artery (60 min) (transient MCAO). Administration of a TAT-modified form of a DNA glycosylase (EndoIII) following reperfusion of the brain reduced resultant brain infarct volume. Protection was dose-dependent, BER enzyme specific, and regionally specific (more effective via the jugular vein). EndoIII is compatible with tissue plasminogen activator (tPA). The time window of a single dose of EndoIII effect is 3 h following reperfusion onset. These data suggest a novel approach to enhance protection of reperfused brain in the setting of revascularization procedures (thrombectomy or thrombolytic therapy) following stroke.</jats:p>
収録刊行物
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- Translational Stroke Research
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Translational Stroke Research 10 (6), 664-671, 2018-12-08
Springer Science and Business Media LLC
