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脑血管损伤诱导淋巴浸润脑实质以指导斑马鱼血管再生。

Cerebrovascular Injuries Induce Lymphatic Invasion into Brain Parenchyma to Guide Vascular Regeneration in Zebrafish.

机构信息

Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.

Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.

出版信息

Dev Cell. 2019 Jun 3;49(5):697-710.e5. doi: 10.1016/j.devcel.2019.03.022. Epub 2019 Apr 18.

DOI:10.1016/j.devcel.2019.03.022
PMID:31006646
Abstract

Damage to regional cerebrovascular networks and neuronal tissues occurs during acute cerebrovascular diseases, such as ischemic stroke. The promotion of vascular regeneration is the most promising therapeutic approach. To understand the cellular and molecular mechanisms underlying brain vascular regeneration, we developed two zebrafish cerebrovascular injury models using genetic ablation and photochemical thrombosis. Although brain parenchyma is physiologically devoid of lymphatic vasculature, we found that cerebrovascular injuries induce rapid ingrowth of meningeal lymphatics into the injured parenchyma. The ingrown lymphatics on one hand become lumenized to drain interstitial fluid to resolve brain edema and on the other hand act as "growing tracks" for nascent blood vessels. The ingrown lymphatic vessels undergo apoptosis and clearance after cerebrovascular regeneration. This study reveals a pathological function of meningeal lymphatics, through previously unexpected ingrowth into brain parenchyma and a newly identified lymphatic function as vascular "growing tracks."

摘要

在急性脑血管疾病(如缺血性中风)中,区域脑血管网络和神经元组织会受到损伤。促进血管再生是最有前途的治疗方法。为了了解脑血管再生的细胞和分子机制,我们使用基因消融和光化学血栓形成开发了两种斑马鱼脑血管损伤模型。尽管脑实质在生理上没有淋巴管系统,但我们发现脑血管损伤会诱导脑膜淋巴管迅速侵入损伤的实质。一方面,侵入的淋巴管管腔化以排出间质液以解决脑水肿,另一方面,它们充当新生血管的“生长轨道”。在脑血管再生后,侵入的淋巴管经历细胞凋亡和清除。这项研究揭示了脑膜淋巴管的一种病理功能,即以前未预料到的侵入脑实质,并发现了淋巴管作为血管“生长轨道”的新功能。

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