Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, U.S.A.
Division of Pediatric Critical Care, Children's Hospital of Michigan, Central Michigan University, Detroit, MI 48201, U.S.A.
Biochem Soc Trans. 2022 Oct 31;50(5):1377-1388. doi: 10.1042/BST20220446.
Ischemic stroke affects over 77 million people annually around the globe. Due to the blockage of a blood vessel caused by a stroke, brain tissue becomes ischemic. While prompt restoration of blood flow is necessary to save brain tissue, it also causes reperfusion injury. Mitochondria play a crucial role in early ischemia-reperfusion injury due to the generation of reactive oxygen species (ROS). During ischemia, mitochondria sense energy depletion and futilely attempt to up-regulate energy production. When reperfusion occurs, mitochondria become hyperactive and produce large amounts of ROS which damages neuronal tissue. This ROS burst damages mitochondria and the cell, which results in an eventual decrease in mitochondrial activity and pushes the fate of the cell toward death. This review covers the relationship between the mitochondrial membrane potential (ΔΨm) and ROS production. We also discuss physiological mechanisms that couple mitochondrial energy production to cellular energy demand, focusing on serine 47 dephosphorylation of cytochrome c (Cytc) in the brain during ischemia, which contributes to ischemia-reperfusion injury. Finally, we discuss the use of near infrared light (IRL) to treat stroke. IRL can both stimulate or inhibit mitochondrial activity depending on the wavelength. We emphasize that the use of the correct wavelength is crucial for outcome: inhibitory IRL, applied early during reperfusion, can prevent the ROS burst from occurring, thus preserving neurological tissue.
每年，全球有超过 7700 万人受到缺血性中风的影响。由于中风导致血管阻塞，脑组织会发生缺血。虽然为了挽救脑组织，及时恢复血液流动是必要的，但这也会导致再灌注损伤。由于活性氧（ROS）的产生，线粒体在早期缺血再灌注损伤中起着至关重要的作用。在缺血期间，线粒体感知能量耗竭，并徒劳地试图上调能量产生。当再灌注发生时，线粒体变得过度活跃并产生大量的 ROS，从而损害神经元组织。这种 ROS 爆发会损害线粒体和细胞，最终导致线粒体活性的降低，并使细胞的命运走向死亡。这篇综述涵盖了线粒体膜电位（ΔΨm）与 ROS 产生之间的关系。我们还讨论了将线粒体能量产生与细胞能量需求相耦合的生理机制，重点讨论了脑缺血期间细胞色素 c（Cytc）丝氨酸 47 去磷酸化，这有助于缺血再灌注损伤。最后，我们讨论了近红外光（IRL）在治疗中风中的应用。IRL 可以根据波长刺激或抑制线粒体活性。我们强调，正确波长的使用对于结果至关重要：在再灌注早期应用抑制性 IRL 可以防止 ROS 爆发的发生，从而保护神经组织。
