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Cytochrome c oxidase‐modulatory near‐infrared light penetration into the human brain: Implications for the noninvasive treatment of ischemia/reperfusion injury
IUBMB Life ( IF 3.7 ) Pub Date : 2020-11-09 , DOI: 10.1002/iub.2405
Paul T Morse 1 , Dennis J Goebel 2 , Junmei Wan 1 , Samuel Tuck 1, 3 , Lara Hakim 1 , Charlotte L Hüttemann 1 , Moh H Malek 4 , Icksoo Lee 5 , Thomas H Sanderson 3 , Maik Hüttemann 1, 6
Affiliation  

Near-infrared light (IRL) has been evaluated as a therapeutic for a variety of pathological conditions, including ischemia/reperfusion injury of the brain, which can be caused by an ischemic stroke or cardiac arrest. Strategies have focused on modulating the activity of mitochondrial electron transport chain (ETC) enzyme cytochrome c oxidase (COX), which has copper centers that broadly absorb IRL between 700 and 1,000 nm. We have recently identified specific COX-inhibitory IRL wavelengths that are profoundly neuroprotective in rodent models of brain ischemia/reperfusion through the following mechanism: COX inhibition by IRL limits mitochondrial membrane potential hyperpolarization during reperfusion, which otherwise causes reactive oxygen species (ROS) production and cell death. Prior to clinical application of IRL on humans, IRL penetration must be tested, which may be wavelength dependent. In the present study, four fresh (unfixed) cadavers and isolated cadaver tissues were used to examine the transmission of infrared light through human biological tissues. We conclude that the transmission of 750 and 940 nm IRL through 4 cm of cadaver head supports the viability of IRL to treat human brain ischemia/reperfusion injury and is similar for skin with different skin pigmentation. We discuss experimental difficulties of working with fresh cadavers and strategies to overcome them as a guide for future studies.

中文翻译:

细胞色素 c 氧化酶调节近红外光进入人脑:对缺血/再灌注损伤无创治疗的意义

近红外光 (IRL) 已被评估为各种病理状况的治疗剂,包括可能由缺血性中风或心脏骤停引起的大脑缺血/再灌注损伤。策略的重点是调节线粒体电子传递链 (ETC) 酶细胞色素 c 氧化酶 (COX) 的活性,该酶具有铜中心,可广泛吸收 700 至 1,000 nm 之间的 IRL。我们最近通过以下机制确定了特定的 COX 抑制 IRL 波长,它们在脑缺血/再灌注的啮齿动物模型中具有深刻的神经保护作用:IRL 的 COX 抑制限制了再灌注过程中的线粒体膜电位超极化,否则会导致活性氧 (ROS) 的产生和细胞死亡。在将 IRL 应用于人体之前,必须测试 IRL 穿透,这可能与波长有关。在本研究中,使用四具新鲜(未固定)尸体和分离的尸体组织来检查红外光通过人体生物组织的传输。我们得出结论,750 和 940 nm IRL 通过 4 cm 尸体头部的传输支持 IRL 治疗人脑缺血/再灌注损伤的可行性,并且对于具有不同皮肤色素沉着的皮肤是相似的。我们讨论了使用新鲜尸体的实验困难和克服它们的策略,作为未来研究的指南。我们得出结论,750 和 940 nm IRL 通过 4 cm 尸体头部的传输支持 IRL 治疗人脑缺血/再灌注损伤的可行性,并且对于具有不同皮肤色素沉着的皮肤是相似的。我们讨论了使用新鲜尸体的实验困难和克服它们的策略,作为未来研究的指南。我们得出结论,750 和 940 nm IRL 通过 4 cm 尸体头部的传输支持 IRL 治疗人脑缺血/再灌注损伤的可行性,并且对于具有不同皮肤色素沉着的皮肤是相似的。我们讨论了使用新鲜尸体的实验困难和克服它们的策略,作为未来研究的指南。
更新日期:2020-11-09
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