Spatiotemporal dynamic changes of meningeal microenvironment influence meningeal lymphatic function following subarachnoid hemorrhage: from inflammatory response to tissue remodeling

作者：Bingrui Zhu, Changming Liu, Ming Luo, Jiarui Chen, Sixuan Tian, Tiantong Zhan, Yibo Liu, Haocheng Zhang, Zhen Wang, Jianmin Zhang, Yuanjian Fang, Sheng Chen, Xiaoyu Wang · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03460-0 · 被引用次数：16 · 研究领域：Cerebrospinal fluid and hydrocephalus、Intracranial Aneurysms: Treatment and Complications、Neurogenesis and neuroplasticity mechanisms

BACKGROUND: Meningeal lymphatic vessels (mLVs) play a critical role in clearing erythrocytes from the subarachnoid space and immune cells from the brain parenchyma following subarachnoid hemorrhage (SAH). However, the drainage function of mLVs is impaired during the acute stage after SAH and gradually recovers in the subacute phase. We aimed to investigate the meningeal transcriptional response post-SAH and elucidate the dynamic influence of meningeal microenvironment on meningeal lymphatic function. METHODS: We employed bioinformatics analysis of single-cell RNA sequencing and spatial transcriptomics to characterize the spatiotemporal dynamic changes in the early meningeal microenvironment post-SAH. In a mouse model of SAH, the early dynamic changes of the meningeal immune cells and the potential growth factor that promoted the early repair of the mLVs were further investigated and validated. RESULTS: During the acute phase, myeloid cells early infiltrated the meninges and triggered inflammatory responses. In the subacute phase, the fibroblast population expanded significantly, contributing to tissue remodeling. The interplay between immune cells and fibroblasts regulated cell migration and phenotypic transition, potentially affecting the function of mLVs. Notably, placental growth factor (PGF) emerged as the most prominent ligand within the VEGF signaling pathway received by meningeal lymphatic endothelial cells (mLECs) post-SAH. This signaling event was associated with the...