Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
J Cereb Blood Flow Metab. 2020 Feb;40(2):263-275. doi: 10.1177/0271678X18822921. Epub 2019 Jan 9.
The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that mice develop significantly fewer meningeal LVs than mice. Again, meningeal lymphangiogenesis occurs in the alymphatic zone lateral to the sagittal sinus only after PT-induced stroke in mice. Interestingly, mice develop larger stroke volumes than mice after tMCAo, but not after PT. Our results reveal differences between PT and tMCAo models of stroke and underscore the need to consider method of stroke induction when investigating the role of meningeal lymphatics. Taken together, our data indicate that ischemic injury can induce the growth of meningeal LVs and that the absence of these LVs can impact post-stroke outcomes.
脑膜淋巴管 (LVs) 的发现引起了人们对其在中枢神经系统疾病中作用的兴趣。与外周 LVs 相似,脑膜 LVs 的发育依赖于血管内皮生长因子受体-3 (VEGFR3) 信号通路。在这里,我们描述了中风对脑膜 LVs 的影响,以及脑膜淋巴管发育不良对中风后结局的影响。我们发现,光血栓形成 (PT),而不是短暂性大脑中动脉闭塞 (tMCAo),会诱导年轻雄性 C57Bl/J6 小鼠脑膜淋巴管生成。我们还发现,与 小鼠相比, 小鼠的脑膜 LVs 数量明显减少。同样,只有在 PT 诱导的中风后, 小鼠的矢状窦侧无淋巴管区才会发生脑膜淋巴管生成。有趣的是,与 tMCAo 后相比, 小鼠在 tMCAo 后发生中风的体积更大,但在 PT 后则不然。我们的结果揭示了 PT 和 tMCAo 中风模型之间的差异,并强调在研究脑膜淋巴管的作用时,需要考虑中风诱导的方法。总之,我们的数据表明,缺血性损伤可以诱导脑膜 LVs 的生长,而这些 LVs 的缺失会影响中风后的结局。