Novel neuroprotective tetramethylpyrazine analog T-006 promotes neurogenesis and neurological restoration in a rat model of stroke

Novel neuroprotective tetramethylpyrazine analog T-006 promotes neurogenesis and neurological restoration in a rat model of stroke
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新型神经保护剂四甲基吡嗪类似物 T-006 促进中风大鼠模型的神经发生和神经恢复

DOI:
10.1097/wnr.0000000000001256
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发表时间:
2019-06
期刊:
影响因子:
1.7
通讯作者:
Zhang Zaijun
Zhang Zaijun
中科院分区:
医学4区
文献类型:
--
作者:
Wu Liangmiao;Cao Jie;Li Ning;Chen Haiyun;Liu Wei;Zhang Gaoxiao;Liu Yu;Wang Yuqiang;Sun Yewei;Zhang Zaijun

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神经元死亡是脑缺血后发生的有害病理变化之一,可导致短暂或永久的神经功能缺损。四甲基吡嗪类似物T-006已被证明是一种多功能神经保护剂,但其神经保护作用及其作用机制尚未在缺血性中风模型大鼠中进行研究。本研究采用一系列行为学和分子生物学试验研究了T-006在大鼠脑卒中模型中的神经保护作用。结果表明,T-006治疗显著改善了神经功能和行为。免疫荧光双染显示T-006明显增加NeuN+/BrdU+、Nestin+/BrdU+和DCX+/BrdU+细胞的数量,并诱导神经元再生。蛋白质印迹分析表明,T-006上调神经发生相关的蛋白质表达的突触后密度蛋白95,脑源性神经营养因子,突触素,髓鞘碱性蛋白。总的来说,这些数据表明,T-006刺激大脑中动脉闭塞大鼠的神经发生并恢复神经功能。
Neuronal death is among the deleterious pathological changes that occur after cerebral ischemia and can lead to transient or permanent neurological deficits. The tetramethylpyrazine analog T-006 has been shown to be a multifunctional neuroprotective agent; however, its neuroprotective effect and mechanism of action have not been studied in ischemic stroke model rats. This study investigated the neuroprotective effects of T-006 in rat stroke model using a battery of behavioral and molecular biological tests. Results indicated that T-006 treatment significantly improved neurological function and behavior. Double immunofluorescence staining showed that T-006 visibly improved the number of NeuN+/BrdU+, Nestin+/BrdU+, and DCX+/BrdU+ cells and induced neuronal regeneration. Western blot analyses indicated that T-006 upregulated neurogenesis-related protein expression of postsynaptic density protein 95, brain-derived neurotrophic factor, synaptophysin, and myelin basic protein. Collectively, these data suggest that T-006 stimulated neurogenesis in rats with middle cerebral artery occlusion and restored neurological functions.
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