Project description:Previous studies have shown that the vascular system regulates brain clearance via arterial blood flow and the lymphatic drainage of CSF. Here, we examined the hypothesis that cerebral venous blood flow may participate in brain clearance as an intermediate compartment between the arterial and lymphatic poles of the vascular system. Transcriptomic analyses provided insights into the molecular mechanisms driving dural lymphatic remodeling within the dura mater.
Project description:To investigate cellular landscape of dural immune cells, dural immune cells from 30 P28 male mice and 30 P7 male mice were FACS sorted and single-cell RNA seqs were performed
Project description:To investigate different responses of dural macrophage subsets to systemic viral infection, we collected the dura mater from mice 12 h after systemic LCMV infection and macrophages were sorted
Project description:While macrophages in the meningeal compartments of the central nervous system (CNS) has been comprehensively characterized under steady state, studying their contribution to physiological and pathological processes has been severely hampered by the lack of specific targeting tools in vivo. Recent findings have shown that the dural sinus and its adjacent lymphatic vessels act as a neuroimmune interface. Notably, the cellular and functional heterogeneity of extrasinusoidal dural macrophages outside this immune hub is currently unclear. Therefore, we comprehensively characterized these cells using single-cell transcriptomics, fate mapping, confocal imaging, clonal analysis and transgenic mouse lines. Extrasinusoidal dural macrophages were clearly distinct from leptomeningeal and CNS parenchymal macrophages in terms of their origin, expansion kinetics and transcriptional profiles. Lastly, functional studies demonstrated that during autoimmune neuroinflammation, extrasinusoidal dural macrophages perform efferocytosis of granulocytes. Our results highlight a previously unappreciated myeloid cell diversity and provide insights into the brain’s innate immune system.
Project description:Purpose: Profile global gene expression of intestinal lymphatics to compare with published datasets Methods: Intestinal tissues were digested, lymphatic endothelial cells were sorted using lymphatic markers including CD31, Podoplanin, Lyve1. Total RNA was isolated from sorted cells using the Direct-Zol RNA MiniPrep kit (Zymo). Samples were submitted for bulk RNA-Sequencing. Conclusions: Gobal gene expression profile of intestinal lymphatics for further comparison with published datasets
Project description:To determine whether dural fibroblasts (DuF) under IL-1β-mediated wound conditions, release pro-angiogenic factors, and promote angiogenic properties in human endothelial cells (ECs). DuF were stimulated by pro-inflammatory cytokines interleukin (IL)-1β, and transcriptome sequencing was then used to identify the differentially expressed genes in the DuF with/without IL-1β stimulation (DuFCon/DuFIL1b)
Project description:Major depressive disorder is one of the most common mental health conditions. Meningeal lymphatics are essential for drainage of molecules in the cerebrospinal fluid to the peripheral immune system. Their potential role in depression-like behaviour has not been investigated. Here, we show in mice, sub-chronic variable stress as a model of depression-like behaviour impairs meningeal lymphatics in females but not in males. Manipulations of meningeal lymphatics regulate the sex difference in the susceptibility to stress-induced depression- and anxiety-like behaviors in mice, as well as alterations of the medial prefrontal cortex and the ventral tegmental area, brain regions critical for emotional regulation. Together, our findings suggest meningeal lymphatic impairment contributes to susceptibility to stress in mice, and that restoration of the meningeal lymphatics might have potential for modulation of depression-like behaviour.
Project description:A major challenge in Spinal Dural Arteriovenous Fistula (SDAVF) was its timely diagnosis, but no specific predictive biomarkers were known. In the discovery cohort (case, n=8 vs. control, n=8), we used cerebrospinal fluid (CSF) and paired plasma samples to identify differentially expressed proteins by label-free quantitative proteomics. Further bioinformatics enrichment analyses were performed to screen target proteins. Finally, it was validated by ELISA experiment in two of the new cohort (case, n=17 vs. control, n=9).
Project description:BackgroundRecent studies have suggested alternative cerebrospinal fluid (CSF) clearance pathways for brain parenchymal metabolic waste products. One fundamental but relatively under-explored component of these pathways is the anatomic region surrounding the superior sagittal sinus, which has been shown to have relevance to trans-arachnoid molecular passage. This so-called parasagittal dural (PSD) space may play a physiologically significant role as a distal intracranial component of the human glymphatic circuit, yet fundamental gaps persist in our knowledge of how this space changes with normal aging and intracranial bulk fluid transport.MethodsWe re-parameterized MRI methods to assess CSF circulation in humans using high resolution imaging of the PSD space and phase contrast measures of flow through the cerebral aqueduct to test the hypotheses that volumetric measures of PSD space (1) are directly related to CSF flow (mL/s) through the cerebral aqueduct, and (2) increase with age. Multi-modal 3-Tesla MRI was applied in healthy participants (n = 62; age range = 20-83 years) across the adult lifespan whereby phase contrast assessments of CSF flow through the aqueduct were paired with non-contrasted T1-weighted and T2-weighted MRI for PSD volumetry. PSD volume was extracted using a recently validated neural networks algorithm. Non-parametric regression models were applied to evaluate how PSD volume related to tissue volume and age cross-sectionally, and separately how PSD volume related to CSF flow (significance criteria: two-sided p < 0.05).ResultsA significant PSD volume enlargement in relation to normal aging (p < 0.001, Spearman's-[Formula: see text] = 0.6), CSF volume (p < 0.001, Spearman's-[Formula: see text] = 0.6) and maximum CSF flow through the aqueduct of Sylvius (anterograde and retrograde, p < 0.001) were observed. The elevation in PSD volume was not significantly related to gray or white matter tissue volumes. Findings are consistent with PSD volume increasing with age and bulk CSF flow.ConclusionsFindings highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Additionally, findings demonstrate that PSD volume increases with age and relates to CSF volume and bi-directional flow. Values reported should provide useful normative ranges for how PSD volume adjusts with age, which will serve as a necessary pre-requisite for comparisons to persons with neurodegenerative disorders.