Neuroprotection by Vitamin C Against Ethanol-Induced Neuroinflammation Associated Neurodegeneration in the Developing Rat Brain
Neuroprotection by Vitamin C Against Ethanol-Induced Neuroinflammation Associated Neurodegeneration in the Developing Rat Brain
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DOI：
10.2174/1871527315666151110130139
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发表时间：
2016-01-01
影响因子：
3
通讯作者：
Kim, Myeong O.
中科院分区：
文献类型：
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作者：
Ahmad, Ashfaq;Shah, Shahid A.;Kim, Myeong O.
乙醇诱导氧化应激，在早期发育期暴露于乙醇会导致神经细胞死亡，从而导致几种神经系统疾病。我们以前报道，维生素C可以防止乙醇诱导的发育中的大鼠脑细胞凋亡。在这里，我们扩展了我们的研究，以了解维生素C对乙醇诱导的氧化应激，神经炎症介导的神经变性在出生后第7天（PND 7）大鼠的治疗效果。单次皮下注射乙醇（5g/kg）可显著诱导生后7天大鼠产生活性氧（ROS），激活小胶质细胞和星形胶质细胞，并诱导不同的凋亡标志物。另一方面，由于其自由基清除特性，维生素C处理显着减少活性氧的产生，抑制活化的小胶质细胞和星形胶质细胞，并逆转其他变化，包括升高的Bax/Bcl-2比值，细胞色素c和不同的caspase如caspase-9和caspase-3在发育中的大鼠脑中由乙醇诱导的水平。此外，维生素C处理还减少了乙醇诱导的聚[ADP-核糖]聚合酶1（PARP-1）活化和神经变性，如PND 7大鼠脑中Flouro-Jade-B和Nissl染色的神经元细胞死亡所示。这些发现表明，维生素C减轻了乙醇诱导的氧化应激，神经炎症和凋亡神经元丢失，并可能有利于防止乙醇对大脑发育的损害作用。
Ethanol induces oxidative stress and its exposure during early developmental age causes neuronal cell death which leads to several neurological disorders. We previously reported that vitamin C can protect against ethanol-induced apoptotic cell death in the developing rat brain. Here, we extended our study to understand the therapeutic efficacy of vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7 (PND7) rat. A single episode of ethanol (5g/kg) subcutaneous administration to postnatal day 7 rat significantly induced the production of reactive oxygen species (ROS), and activated both microglia and astrocytes followed by the induction of different apoptotic markers. On the other hand, due to its free radical scavenging properties, vitamin C treatment significantly reduced the production of reactive oxygen species, suppressed both activated microglia and astrocytes and reversed other changes including elevated level of Bax/Bcl-2 ratio, cytochrome c and different caspases such as caspase-9 and caspase-3 induced by ethanol in developing rat brain. Moreover, vitamin C treatment also reduced ethanol-induced activation of Poly [ADP-Ribose] Polymerase 1(PARP-1) and neurodegeneration as evident from Flouro-Jade-B and Nissl stainined neuronal cell death in PND7 rat brain. These findings suggest that vitamin C mitigated ethanol-induced oxidative stress, neuroinflammation and apoptotic neuronal loss and may be beneficial against ethanol damaging effects in brain development.