延迟亚低温对缺血再灌注脑损伤后神经功能恢复和神经发生的影响

发布时间：2018-04-30 09:18

  本文选题：延迟亚低温 + 神经发生　； 参考：《浙江大学》2016年硕士论文

【摘要】：研究背景：对于缺血脑损伤,亚低温治疗是一种强大的神经保护策略。但病人往往是发病后才运送到医疗单位,延误了“最佳”低温治疗时机。这种延迟亚低温是否能促进神经功能恢复及其机制需要进一步阐明。神经发生(neurogenesis)是一种可能的低温保护机制。脑缺血后侧脑室室管膜下区(SVZ)和海马齿状回(DG)区细胞增殖增加；神经祖细胞迁移途径发生了改变,大量新增殖的细胞迁移至缺血损伤边缘；一小部分细胞能存活并分化为成熟的神经元或星形胶质细胞。缺血后亚低温能抑制氨基酸和单胺神经递质的过度释放、及炎症反应,但是否调节缺血后神经前体细胞的增殖和迁移还知之甚少。本课题首先探讨缺血后延迟亚低温对脑梗死面积和神经功能恢复的影响；其次研究检测脑缺血后延迟亚低温对细胞增殖和分化的影响。方法：制备局灶性脑缺血再灌注模型,缺血再灌注后15mmin降低中心温度到30℃维持3h来诱导延迟亚低温。应用行为学测试、溴脱氧尿苷(BrdU)标记、激光共聚焦显微镜细胞谱分析等方法来探讨延迟亚低温治疗对神经功能恢复和神经发生的影响。结果：延迟亚低温不能降低缺血梗死面积,但能促进神经功能恢复。同常温模型组相比,延迟亚低温能显著提高脑缺血后3h(缺血后立即给予BrdU标记一次)缺血侧SVZ区的新生细胞数(P0.05)。延迟亚低温能显著提高缺血后7和14d(缺血后给予BrdU连续7d标记)缺血侧SVZ区的新生细胞积聚数(P0.05)；延迟亚低温能显著提高缺血后7d缺血侧DG区的新生细胞积聚数(P0.05),却显著降低14d缺血侧DG区的新生细胞积聚数(P0.05)；对缺血半梗死区新生细胞聚集无明显影响。另外,延迟亚低温能提高缺血后一些时间点新生细胞与一些神经细胞标记物共定位的比例,包括DCX(未成熟神经元标记物)、Nestin(未成熟神经元或胶质细胞标志物)、GFAP (成熟星形胶质细胞标记物)、NG2(少突胶质细胞标记物)和NeuN(成熟神经元标记物)。结论：(1)延迟亚低温可促进神经功能恢复。(2)延迟亚低温可通过促进缺血后细胞增殖和新生细胞积聚、改变新生细胞的最终命运来减轻缺血性损伤、促进脑损伤的修复。
[Abstract]:Background: mild hypothermia therapy is a powerful neuroprotective strategy for ischemic brain injury. But patients are often transported to medical units after onset, delaying the "best" timing of hypothermia treatment. Whether this delayed mild hypothermia can promote the recovery of neural function and its mechanism need further clarification. Neurogenetics is a possible hypothermia protective mechanism. After cerebral ischemia, the proliferation of SVZ (subependymal area) and DGG (dentate gyrus) increased, the migration pathway of neural progenitor cells changed, and a large number of newly proliferated cells migrated to the edge of ischemic injury. A small number of cells can survive and differentiate into mature neurons or astrocytes. Mild hypothermia after ischemia can inhibit the excessive release of amino acids and monoamine neurotransmitters, and inflammatory response, but it is not known whether it regulates the proliferation and migration of neural precursor cells after ischemia. In this study, the effects of delayed mild hypothermia after ischemia on cerebral infarction size and neural function recovery were investigated, and the effects of delayed mild hypothermia on cell proliferation and differentiation after cerebral ischemia were studied. Methods: the focal cerebral ischemia-reperfusion model was established. 15mmin decreased the central temperature to 30 鈩，

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