Effects of Controlled Cortical Impact on the Mouse Brain Vasculome
Effects of Controlled Cortical Impact on the Mouse Brain Vasculome
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DOI：
10.1089/neu.2015.4101
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发表时间：
2016-07-15
影响因子：
4.2
通讯作者：
Lo, Eng H.
中科院分区：
文献类型：
--
作者：
Guo, Shuzhen;Lok, Josephine;Lo, Eng H.
血管中的扰动在脑损伤和神经变性的病理生理学中起关键作用。在这里，我们使用系统的全基因组转录组筛选方法来研究小鼠脑创伤后的血管组。使小鼠经受受控的皮质撞击，并在损伤后24小时提取脑用于分析。去除创伤性病变的核心，然后从非直接损伤的同侧皮质分离皮质微血管。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中存在广泛的反应。上调途径包括参与炎症和细胞外基质过程调节的途径。减少的途径包括参与代谢调节、线粒体功能和转运系统的途径。这些发现表明，微血管扰动可能是广泛的，不一定局限于直接损伤本身的核心区域，并可能进一步提供更广泛的基因网络背景下，现有的知识炎症，代谢和血脑屏障改变脑外伤后。需要进一步努力以更高的空间和时间分辨率绘制从急性期到延迟期创伤后的血管。研究血管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。
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.