Low-level light in combination with metabolic modulators for effective therapy of injured brain
Low-level light in combination with metabolic modulators for effective therapy of injured brain
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DOI：
10.1038/jcbfm.2015.87
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发表时间：
2015-09-01
影响因子：
6.3
通讯作者：
Wu, Mei X.
中科院分区：
文献类型：
--
作者：
Dong, Tingting;Zhang, Qi;Wu, Mei X.
血管损伤经常发生在受伤的脑部，导致缺氧，并与临床结果不佳有关。我们发现，在低氧条件下，神经元糖酵解水平高，三磷酸腺苷生成减少，活性氧物种的形成和细胞凋亡增加。值得注意的是，这些不良事件可以通过非侵入性的低强度光(LLL)暴露在受损的大脑中而显著逆转。低强度光照维持线粒体膜电位，抑制细胞色素c在低氧细胞中的渗漏，并保护细胞免受凋亡，突显了LLL的独特性质。在体内和体外，通过与代谢底物如丙酮酸或乳酸的结合，LLL的作用进一步增强。联合治疗将受损小鼠的记忆和学习活动保持在正常水平，而其他治疗显示出这些认知功能的部分或严重缺陷。根据学习记忆功能的良好保护，联合治疗可完全保护主要负责学习记忆的海马区，与对照组小鼠因继发性损伤而导致的严重海马区组织丢失形成鲜明对比。这些数据清楚地表明，能量代谢调节剂可以相加或协同地增强LLL对能量产生不足的组织样损伤脑的治疗效果。
Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissue-like injured brain.