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局灶性脑缺血诱导小鼠神经母细胞和神经元数量及血管生成因子密度的全球亚急性变化。

Focal Cerebral Ischemia Induces Global Subacute Changes in the Number of Neuroblasts and Neurons and the Angiogenic Factor Density in Mice.

机构信息

Department of Pharmacology, Faculty of Medicine, University of Latvia, Raina blvd. 19, LV-1586 Riga, Latvia.

Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilian University Munich, 81377 München, Germany.

出版信息

Medicina (Kaunas). 2023 Dec 14;59(12):2168. doi: 10.3390/medicina59122168.

Abstract

: Dissecting the complex pathological cascade of an ischemic stroke in preclinical models is highly warranted to understand the course of this disease in humans. Neurogenesis and angiogenesis are integral for post-stroke recovery, yet it is not clear how these processes are altered months after an ischemic stroke. In this study, we investigated the changes that take place subacutely after focal cerebral ischemia in experimental adult male mice. : Male 12-week-old C57BL/6 mice underwent a 60 min long fMCAo or sham surgery. Two months after the procedure, we examined the immunohistochemistry to assess the changes in neuroblast (DCX) and differentiated neuron (NeuN) numbers, as well as the density of the pro-angiogenic factor VEGF. : We found decreased neuroblast numbers in both brain hemispheres of the fMCAo mice: by more than 85% in the dentate gyrus and by more than 70% in the subventricular zone. No neuroblasts were found in the contralateral hemisphere of the fMCAO mice or the sham controls, but a small population was detected in the ipsilateral ischemic core of the fMCAo mice. Intriguingly, the number of differentiated neurons in the ipsilateral ischemic core was lower by 20% compared to the contralateral hemisphere. VEGF expression was diminished in both brain hemispheres of the fMCAo mice. : Our current report shows that focal cerebral ischemia induces changes in neuroblast numbers and the pro-angiogenic factor VEGF in both cerebral hemispheres 2 months after an fMCAo in mice. Our data show that focal cerebral ischemia induces a long-term regenerative response in both brain hemispheres.

摘要

在临床前模型中剖析缺血性中风的复杂病理级联反应,对于了解人类中风的病程非常有必要。神经发生和血管生成对于中风后恢复至关重要,但尚不清楚这些过程在缺血性中风后数月会发生怎样的变化。在这项研究中,我们研究了成年雄性小鼠局灶性大脑中动脉闭塞(fMCAo)后亚急性期发生的变化。

雄性 12 周龄 C57BL/6 小鼠接受 60 分钟长的 fMCAo 或假手术。在手术后 2 个月,我们通过免疫组织化学检查评估神经母细胞(DCX)和分化神经元(NeuN)数量以及促血管生成因子 VEGF 的密度的变化。

我们发现 fMCAo 小鼠两侧大脑半球的神经母细胞数量减少:齿状回减少超过 85%,侧脑室下区减少超过 70%。fMCAo 小鼠对侧半球或假手术对照均未发现神经母细胞,但在 fMCAo 小鼠同侧缺血核心区检测到一小部分。有趣的是,同侧缺血核心区的分化神经元数量比对侧半球减少了 20%。VEGF 表达在 fMCAo 小鼠两侧大脑半球均减少。

我们目前的报告表明,局灶性大脑中动脉闭塞在小鼠 fMCAo 2 个月后会导致两侧大脑半球的神经母细胞数量和促血管生成因子 VEGF 发生变化。我们的数据表明,局灶性大脑中动脉闭塞会在两侧大脑半球诱导长期的再生反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8366/10745011/d4de1b85d75c/medicina-59-02168-g001.jpg

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