Yu Zhanyang, Liu Ning, Zhao Jianhua, Li Yadan, McCarthy Thomas J, Tedford Clark E, Lo Eng H, Wang Xiaoying
Departments of Neurology and Radiology, Neuroprotection Research Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA,
Metab Brain Dis. 2015 Apr;30(2):491-6. doi: 10.1007/s11011-014-9515-6. Epub 2014 Mar 6.
Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neurodegeneration. However, the potential molecular mechanisms of neuroprotection with NIR remain poorly defined. In this study, we tested the hypothesis that low intensity NIR may attenuate hypoxia/ischemia-induced mitochondrial dysfunction in neurons. Primary cortical mouse neuronal cultures were subjected to 4 h oxygen-glucose deprivation followed by reoxygenation for 2 h, neurons were then treated with a 2 min exposure to 810-nm NIR. Mitochondrial function markers including MTT reduction and mitochondria membrane potential were measured at 2 h after treatment. Neurotoxicity was quantified 20 h later. Our results showed that 4 h oxygen-glucose deprivation plus 20 h reoxygenation caused 33.8 ± 3.4 % of neuron death, while NIR exposure significantly reduced neuronal death to 23.6 ± 2.9 %. MTT reduction rate was reduced to 75.9 ± 2.7 % by oxygen-glucose deprivation compared to normoxic controls, but NIR exposure significantly rescued MTT reduction to 87.6 ± 4.5 %. Furthermore, after oxygen-glucose deprivation, mitochondria membrane potential was reduced to 48.9 ± 4.39 % of normoxic control, while NIR exposure significantly ameliorated this reduction to 89.6 ± 13.9 % of normoxic control. Finally, NIR significantly rescued OGD-induced ATP production decline at 20 min after NIR. These findings suggest that low intensity NIR can protect neurons against oxygen-glucose deprivation by rescuing mitochondrial function and restoring neuronal energetics.
近红外辐射（NIR）能够穿透并以多种方式影响生物系统。最近，一系列实验研究表明，低强度近红外辐射可能保护神经元细胞免受多种类似中风、脑外伤和神经退行性疾病等疾病的损伤。然而，近红外辐射神经保护的潜在分子机制仍不清楚。在本研究中，我们验证了低强度近红外辐射可能减轻缺氧/缺血诱导的神经元线粒体功能障碍这一假说。将原代培养的小鼠皮质神经元进行4小时氧糖剥夺，然后复氧2小时，之后用810纳米近红外辐射照射2分钟。在处理后2小时测量线粒体功能标志物，包括MTT还原和线粒体膜电位。20小时后对神经毒性进行定量分析。我们的结果显示，4小时氧糖剥夺加20小时复氧导致33.8±3.4%的神经元死亡，而近红外辐射照射显著将神经元死亡减少至23.6±2.9%。与常氧对照组相比，氧糖剥夺使MTT还原率降低至75.9±2.7%，但近红外辐射照射显著将MTT还原率恢复至87.6±4.5%。此外，氧糖剥夺后，线粒体膜电位降低至常氧对照组的48.9±4.39%，而近红外辐射照射显著将这种降低改善至常氧对照组的89.6±13.9%。最后，近红外辐射显著挽救了氧糖剥夺诱导的近红外辐射后20分钟时ATP生成的下降。这些发现表明，低强度近红外辐射可通过挽救线粒体功能和恢复神经元能量代谢来保护神经元免受氧糖剥夺的损伤。
