Effect of thrombin preconditioning on migration of subventricular zone-derived cells after intracerebral hemorrhage in rats

Effect of thrombin preconditioning on migration of subventricular zone-derived cells after intracerebral hemorrhage in rats
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凝血酶预处理对大鼠脑出血后室下区来源细胞迁移的影响

DOI:
10.1080/01616412.2016.1210356
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发表时间:
2016-07
影响因子:
1.9
通讯作者:
Zunenng Lu
Zunenng Lu
中科院分区:
医学4区
文献类型:
--
作者:
Shaofeng Zhang;Qin ZHou;Zhenhua Yuan;Zunenng Lu

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目的:探讨凝血酶预处理(TPC)对脑出血(ICH)诱导的脑室下区(SVZ)细胞增殖、迁移和功能的影响,并寻求促进脑出血后内源性神经发生的新策略。方法:雄性sd - dawley大鼠随机分为ICH组、TPC组和对照组。各组大鼠随机分为5个亚组(3-d、7-d、14-d、21-d、28-d亚组)。脑出血是由IV型胶原酶胃内立体定向给药引起的。Brdu标记新生SVZ细胞。培养器官型脑切片,动态观察SVZ细胞在活体脑组织中的迁移情况。用延时显微镜观察dill标记的SVZ细胞在活脑切片中的迁移情况。评估SVZ细胞迁移到受伤的纹状体是否有能力与其他细胞形成突触,大脑切片从每组双immunolabeled Brdu和synapsin。结果:Brdu-positive细胞的数量明显增加了身体的同侧的SVZ TPC和纹状体3天后,达到14天(P < 0.01),持续21天,然后逐渐减少在28天显著差异在每个时间点相比我组(P < 0.01)。观察各组脑切片中dil标记的SVZ细胞在12 h内的迁移情况并进行成像。与ICH组相比,TPC组dill标记的SVZ细胞随时间向纹状体侧移的速度更快(P < 0.01)。我们的研究还表明,TPC在损伤后3至28天内诱导了Brdu和突触素I在同侧纹状体的强共定位。与ICH组相比,TPC使Brdu和synapsin I的共定位出现得更早,持续时间更长。结论:TPC可促进脑出血后SVZ细胞的增殖、迁移和功能,为促进内源性神经发生和开发新的脑出血脑损伤治疗策略提供了新的思路。
Objective: To investigate the effect of thrombin preconditioning (TPC) on the intracerebral hemorrhage (ICH)-induced proliferation, migration, and function of subventriclular zone (SVZ) cells and to find new strategies that enhance endogenous neurogenesis after ICH. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups (ICH, TPC, and control group). Rats of each group were randomly divided into 5 subgroups (3-d, 7-d, 14-d, 21-d, and 28-d subgroup). ICH was caused by intrastrial stereotactic administration of collagenase type IV. Brdu was used to label newborn SVZ cells. Organotypic brain slices were cultured to dynamically observe the migration of SVZ cells at living brain tissue. Migration of Dil-labeled SVZ cells in living brain slices was traced by time-lapse microscopy. To assess whether SVZ cells migrating to injured striatum had the ability to form synapses with other cells, brain slices from each group were double immunolabeled with Brdu and synapsin I. Results: The number of Brdu-positive cells markedly increased in the ipsilateral SVZ and striatum 3 days after TPC, peaked at 14 days (P < 0.01), continued to 21 days, and then gradually decreased at 28 days with significant difference compared to the ICH group at each time point (P < 0.01). Migration of Dil-labeled SVZ cells in brain slices in each group was observed and imaged during a 12-h period. Dil-labeled SVZ cells in the TPC group were observed to migrate laterally toward striatum with time with a faster velocity compared to the ICH group (P < 0.01). Our study also demonstrated that TPC induced strong colocalization of Brdu and synapsin I in the ipsilateral striatum between 3 and 28 days after injury.TPC made colocalization of Brdu and synapsin I appear earlier and continue for a longer time compared to the ICH group. Conclusions: Our results demonstrated that TPC could promote proliferation, migration, and function of SVZ cells after ICH, which may provide a new idea for enhancing endogenous neurogenesis and developing new therapeutic strategies against ICH-induced brain injury.
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发表时间: 2010-02
影响因子: 6.1
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