Cerebrovascular Injuries Induce Lymphatic Invasion into Brain Parenchyma to Guide Vascular Regeneration in Zebrafish
Cerebrovascular Injuries Induce Lymphatic Invasion into Brain Parenchyma to Guide Vascular Regeneration in Zebrafish
复制标题
脑血管损伤诱导淋巴侵入脑实质以引导斑马鱼的血管再生
DOI：
10.1016/j.devcel.2019.03.022
复制
发表时间：
2019-06-03
影响因子：
11.8
通讯作者：
Luo, Lingfei
中科院分区：
文献类型：
--
作者：
Chen, Jingying;He, Jianbo;Luo, Lingfei
局部脑血管网络和神经元组织的损伤发生在急性脑血管疾病（例如缺血性中风）期间。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，我们利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缺乏淋巴管系统，但我们发现脑血管损伤会导致脑膜淋巴管快速向内生长到受伤的实质中。内生的淋巴管一方面变得管腔化以排出间质液以解决脑水肿，另一方面充当新生血管的“生长轨道”。脑血管再生后，向内生长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病理功能，通过先前意想不到的向脑实质内生长和新发现的淋巴管功能作为血管“生长轨迹”。
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."