Imaging the construction of capillary networks in the neonatal mouse brain.
Imaging the construction of capillary networks in the neonatal mouse brain.
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DOI：
10.1073/pnas.2100866118
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发表时间：
2021-06-29
影响因子：
11.1
通讯作者：
Shih AY
中科院分区：
文献类型：
--
作者：
Coelho-Santos V;Berthiaume AA;Ornelas S;Stuhlmann H;Shih AY
血液在整个大脑中的分布是由高度互连的毛细血管网络促进的。然而，建设这些网络所涉及的步骤仍然不清楚。我们使用在体双光子成像通过非侵入性颅窗研究新生小鼠大脑皮层毛细血管网络的工程。我们发现，血管生成活动起源于上行小静脉，经历了一个爆发的发芽在出生后第二周。这种萌芽活动首先建立长路径，将小静脉连接到来自相邻小动脉的血液输入，然后通过大量短程连接扩展毛细血管的相互连接。我们的研究提供了一个实验基础，以了解毛细血管网络是如何形成在活的哺乳动物大脑在出生后的发展。毛细血管网络对于通过大脑的血流分布以及许多其他稳态功能（包括神经血管信号传导和血脑屏障完整性）是必不可少的。因此，毛细血管结构和功能的损伤是许多脑疾病的根源。可视化脑毛细血管网络如何在体内发育可以揭示脑血管生长和修复的先天程序。在这里，我们使用纵向双光子成像，通过非侵入性薄颅骨窗，以研究在小鼠新生儿脑血管发育过程中的血管生成活动的爆发。我们发现，血管生成导致毛细血管网络的形成完全起源于皮质升小静脉。观察到两种血管生成出芽活动：1）早期长距离出芽，直接连接小静脉和上游小动脉输入，建立毛细血管床的主干; 2）短距离出芽，有助于毛细血管床内吻合连接的扩张。所有新生芽都预制有完整的内皮管腔和周细胞覆盖，确保它们在连接到靶血管后立即灌注和稳定。这种毛细血管扩张的大部分仅持续2至3天，并在皮质发育的关键时期促进了血流量的增加。
The distribution of blood throughout the brain is facilitated by highly interconnected capillary networks. However, the steps involved in the construction of these networks has remained unclear. We used in vivo two-photon imaging through noninvasive cranial windows to study the engineering of capillary networks in the cerebral cortex of mouse neonates. We find that angiogenic activity originates at ascending venules, which undergo a burst of sprouting in the second postnatal week. This sprouting activity first establishes long paths to connect venules to blood input from neighboring arterioles, and then expands capillary interconnectivity with a multitude of short-range connections. Our study provides an experimental foundation to understand how capillary networks are shaped in the living mammalian brain during postnatal development. Capillary networks are essential for distribution of blood flow through the brain, and numerous other homeostatic functions, including neurovascular signal conduction and blood–brain barrier integrity. Accordingly, the impairment of capillary architecture and function lies at the root of many brain diseases. Visualizing how brain capillary networks develop in vivo can reveal innate programs for cerebrovascular growth and repair. Here, we use longitudinal two-photon imaging through noninvasive thinned skull windows to study a burst of angiogenic activity during cerebrovascular development in mouse neonates. We find that angiogenesis leading to the formation of capillary networks originated exclusively from cortical ascending venules. Two angiogenic sprouting activities were observed: 1) early, long-range sprouts that directly connected venules to upstream arteriolar input, establishing the backbone of the capillary bed, and 2) short-range sprouts that contributed to expansion of anastomotic connectivity within the capillary bed. All nascent sprouts were prefabricated with an intact endothelial lumen and pericyte coverage, ensuring their immediate perfusion and stability upon connection to their target vessels. The bulk of this capillary expansion spanned only 2 to 3 d and contributed to an increase of blood flow during a critical period in cortical development.
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影响因子：
16.2
作者：
Lacoste B;Comin CH;Ben-Zvi A;Kaeser PS;Xu X;Costa Lda F;Gu C
通讯作者：
Gu C
影响因子：
3.7
作者：
Kim TN;Goodwill PW;Chen Y;Conolly SM;Schaffer CB;Liepmann D;Wang RA
通讯作者：
Wang RA
影响因子：
25
作者：
Blinder, Pablo;Tsai, Philbert S.;Kaufhold, John P.;Knutsen, Per M.;Suhl, Harry;Kleinfeld, David
通讯作者：
Kleinfeld, David
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
DOI：
10.1038/jcbfm.2011.153
发表时间：
2012-02
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
Jespersen SN;Østergaard L
通讯作者：
Østergaard L