Pham Lucynda, Arroum Tasnim, Morse Paul T, Bell Jamie, Malek Moh H, Sanderson Thomas H, Hüttemann Maik
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
Division of Pediatric Critical Care, Children's Hospital of Michigan, Central Michigan University, Detroit, MI 48201, USA.
Antioxidants (Basel). 2025 Sep 15;14(9):1119. doi: 10.3390/antiox14091119.
Ischemia/reperfusion (I/R) injury following stroke results in increased neuronal cell death due to mitochondrial hyperactivity. Ischemia results in loss of regulatory phosphorylations on cytochrome oxidase (COX) and cytochrome of the electron transport chain (ETC), priming COX for hyperactivity. During reperfusion, the ETC operates at maximal speed, resulting in hyperpolarization of the mitochondrial membrane potential (ΔΨ) and reactive oxygen species (ROS) production. We have shown that COX-inhibitory near-infrared light (IRL) provides neuroprotection in small and large animal models of brain I/R injury. IRL therapy is non-invasive and non-pharmacological and does not rely on blood flow. We identified specific wavelengths of IRL, 750 and 950 nm, that inhibit COX activity. To model the mitochondrial effects following neuronal I/R, SH-SY5Y cells underwent oxygen-glucose deprivation/reoxygenation (OGD/R) ± IRL applied at the time of reoxygenation. Untreated cells exhibited ΔΨ hyperpolarization, whereas IRL treated cells showed no significant difference compared to control. IRL treatment suppressed ROS production, decreased the level of cell death, and reduced the time to normalize mitochondrial activity to baseline levels from 4-5 to 2.5 h of reperfusion time. We show that IRL treatment is protective by limiting ΔΨ hyperpolarization and ROS production, and by speeding up cellular recovery.
中风后的缺血/再灌注（I/R）损伤会因线粒体过度活跃导致神经元细胞死亡增加。缺血会导致细胞色素氧化酶（COX）和电子传递链（ETC）中细胞色素的调节性磷酸化丧失，使COX易于过度活跃。在再灌注期间，ETC以最大速度运转，导致线粒体膜电位（ΔΨ）超极化和活性氧（ROS）生成。我们已经表明，COX抑制性近红外光（IRL）在大脑I/R损伤的大小动物模型中提供神经保护作用。IRL疗法是非侵入性且非药物性的，不依赖于血流。我们确定了抑制COX活性的IRL特定波长，即750和950纳米。为了模拟神经元I/R后的线粒体效应，SH-SY5Y细胞经历了氧糖剥夺/复氧（OGD/R），并在复氧时施加或不施加IRL。未处理的细胞表现出ΔΨ超极化，而IRL处理的细胞与对照相比无显著差异。IRL处理抑制了ROS生成，降低了细胞死亡水平，并将线粒体活性恢复到基线水平的时间从再灌注4 - 5小时缩短至2.5小时。我们表明，IRL处理通过限制ΔΨ超极化和ROS生成以及加速细胞恢复而具有保护作用。
