缺血性脑卒中后的线粒体动脉内移植可减少脑梗塞。

IF 2.1 Q3 CLINICAL NEUROLOGY Stroke (Hoboken, N.J.) Pub Date : 2023-05-01 Epub Date: 2023-03-02 DOI:10.1161/svin.122.000644
Pedro Norat, Jennifer D Sokolowski, Catherine M Gorick, Sauson Soldozy, Jeyan S Kumar, Youngrok Chae, Kaan Yagmurlu, Joelle Nilak, Khadijeh A Sharifi, Melanie Walker, Michael R Levitt, Alexander L Klibanov, Zhen Yan, Richard J Price, Petr Tvrdik, M Yashar S Kalani
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引用次数: 0

摘要

背景将自体线粒体移植到缺血组织可减轻缺血和再灌注造成的损伤:我们利用大脑中动脉闭塞的小鼠中风模型,试图评估向缺血脑实质输送存活线粒体的可行性。我们评估了同时用聚焦超声激活微气泡(微气泡的作用是打开血脑屏障)对线粒体输送效果的影响:结果:动脉内递送线粒体后,线粒体分布于中风半球,并融入脑实质中的神经细胞和胶质细胞。与缺血组织中的功能整合相一致,移植的线粒体提高了中风半球中三磷酸腺苷的浓度,缩小了梗死体积,并增加了细胞活力。额外的聚焦超声改善了血脑屏障的开放,但没有出血并发症:我们的研究结果对缺血性中风后介入治疗策略的发展具有重要意义,并为机械性血栓切除术后的治疗提供了一种新的潜在模式。
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Intraarterial Transplantation of Mitochondria After Ischemic Stroke Reduces Cerebral Infarction.

Background-: Transplantation of autologous mitochondria into ischemic tissue may mitigate injury caused by ischemia and reperfusion.

Methods-: Using murine stroke models of middle cerebral artery occlusion, we sought to evaluate feasibility of delivery of viable mitochondria to ischemic brain parenchyma. We evaluated the effects of concurrent focused ultrasound activation of microbubbles, which serves to open the blood-brain barrier, on efficacy of delivery of mitochondria.

Results-: Following intra-arterial delivery, mitochondria distribute through the stroked hemisphere and integrate into neural and glial cells in the brain parenchyma. Consistent with functional integration in the ischemic tissue, the transplanted mitochondria elevate concentration of adenosine triphosphate in the stroked hemisphere, reduce infarct volume and increase cell viability. Additional of focused ultrasound leads to improved blood brain barrier opening without hemorrhagic complications.

Conclusions-: Our results have implications for the development of interventional strategies after ischemic stroke and suggest a novel potential modality of therapy after mechanical thrombectomy.

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