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控制性皮质撞击对小鼠脑血管系统的影响。

Effects of Controlled Cortical Impact on the Mouse Brain Vasculome.

作者信息

Guo Shuzhen, Lok Josephine, Zhao Song, Leung Wendy, Som Angel T, Hayakawa Kazuhide, Wang Qingzhi, Xing Changhong, Wang Xiaoying, Ji Xunming, Zhou Yiming, Lo Eng H

机构信息

1 Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital , Harvard Medical School, Charlestown, Massachusetts.

2 Department of Pediatrics, Massachusetts General Hospital , Harvard Medical School, Boston, Massachusetts.

出版信息

J Neurotrauma. 2016 Jul 15;33(14):1303-16. doi: 10.1089/neu.2015.4101. Epub 2016 Feb 12.

Abstract

Perturbations in blood vessels play a critical role in the pathophysiology of brain injury and neurodegeneration. Here, we use a systematic genome-wide transcriptome screening approach to investigate the vasculome after brain trauma in mice. Mice were subjected to controlled cortical impact and brains were extracted for analysis at 24 h post-injury. The core of the traumatic lesion was removed and then cortical microvesels were isolated from nondirectly damaged ipsilateral cortex. Compared to contralateral cortex and normal cortex from sham-operated mice, we identified a wide spectrum of responses in the vasculome after trauma. Up-regulated pathways included those involved in regulation of inflammation and extracellular matrix processes. Decreased pathways included those involved in regulation of metabolism, mitochondrial function, and transport systems. These findings suggest that microvascular perturbations can be widespread and not necessarily localized to core areas of direct injury per se and may further provide a broader gene network context for existing knowledge regarding inflammation, metabolism, and blood-brain barrier alterations after brain trauma. Further efforts are warranted to map the vasculome with higher spatial and temporal resolution from acute to delayed phase post-trauma. Investigating the widespread network responses in the vasculome may reveal potential mechanisms, therapeutic targets, and biomarkers for traumatic brain injury.

摘要

血管紊乱在脑损伤和神经退行性变的病理生理学中起着关键作用。在此,我们采用系统的全基因组转录组筛选方法来研究小鼠脑外伤后的血管组。对小鼠进行控制性皮质撞击,在损伤后24小时提取大脑进行分析。去除创伤性病变的核心,然后从未直接受损的同侧皮质分离出皮质微血管。与假手术小鼠的对侧皮质和正常皮质相比,我们发现创伤后血管组有广泛的反应。上调的通路包括参与炎症调节和细胞外基质过程的通路。下调的通路包括参与代谢调节、线粒体功能和转运系统的通路。这些发现表明,微血管紊乱可能广泛存在,不一定局限于直接损伤的核心区域本身,并且可能进一步为关于脑外伤后炎症、代谢和血脑屏障改变的现有知识提供更广泛的基因网络背景。有必要进一步努力,以更高的空间和时间分辨率描绘从创伤急性期到延迟期的血管组。研究血管组中广泛的网络反应可能揭示创伤性脑损伤的潜在机制、治疗靶点和生物标志物。

相似文献

1
Effects of Controlled Cortical Impact on the Mouse Brain Vasculome.控制性皮质撞击对小鼠脑血管系统的影响。
J Neurotrauma. 2016 Jul 15;33(14):1303-16. doi: 10.1089/neu.2015.4101. Epub 2016 Feb 12.
2
The vasculome of the mouse brain.小鼠脑的脉管系统。
PLoS One. 2012;7(12):e52665. doi: 10.1371/journal.pone.0052665. Epub 2012 Dec 20.

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Network dysfunction after traumatic brain injury.创伤性脑损伤后的网络功能障碍。
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