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
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DOI：
10.1101/346007
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发表时间：
2018-06
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通讯作者：
Jingying Chen;Jianbo He;Qifen Yang;Yaoguang Zhang;L. Luo
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作者：
Jingying Chen;Jianbo He;Qifen Yang;Yaoguang Zhang;L. Luo
急性脑血管病，如缺血性脑卒中，可引起局部脑血管网络和神经元组织的损伤。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，我们开发了两种斑马鱼脑血管损伤模型，使用基因消融和光化学血栓形成。虽然脑实质在生理上缺乏淋巴管，但我们发现脑血管损伤可诱导脑膜炎细胞快速长入损伤的脑实质。脑内新生血管的形成，一方面可使脑组织腔化，排出组织液，消除脑水肿，另一方面又可作为新生血管的“生长通道”。脑血管再生后，向内生长的淋巴管经历凋亡和清除。这项研究揭示了脑膜炎的病理功能，通过以前意想不到的向内生长到脑实质和一个新确定的淋巴功能作为血管“生长轨道”。脑血管损伤诱导淋巴管长入损伤的脑实质内，长入的淋巴管排出间质液以解决脑水肿新生血管使用长入的淋巴管作为“生长轨道”，长入的淋巴管在血管再生完成后经历凋亡。
Damage to regional cerebrovascular network 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 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 drain interstitial fluid to resolve brain edema, 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”. HIGHLIGHTS Cerebrovascular injuries induce lymphatic ingrowth into the injured brain parenchyma The ingrown lymphatics drain interstitial fluid to resolve brain edema Nascent blood vessels use the ingrown lymphatic vessels as “growing tracks” The ingrown lymphatic vessels undergo apoptosis after vascular regeneration completes