Biology subjects

Noe, F. M.

Publications and source records attributed to Noe, F. M..

3 recordsLinked to original sources

bioRxiv2021

Dorsal skull meningeal lymphatic vessels drain blood-solutes after intracerebral hemorrhage

Drainage of intraparenchymal hematoma is crucial for the treatment of intracerebral hemorrhage (ICH). We investigated here the possible function of the meningeal lymphatic vessels (mLVs) in ICH resolution. Meningeal lymphatics have been reported to be involved in cerebrospinal fluid drainage, but their role in the drainage and clearance of brain parenchyma has not been characterized in details. Using two preclinical models of ICH, mimicking focal cortical ischemic hemorrhage and subcortical extended hemorrhage, we characterized the dynamics of blood drainage through the dorsal mLVs by two-photon real time imaging in awake mice. After ICH induction, we observe the flow of blood-derived components within the mLVs, suggesting that meningeal lymphatics can play a role in facilitating the drainage of the hemorrhage. We also found that local formation of new mLVs is directly correlated with ICH-related neuroinflammation levels. These findings suggest that meningeal lymphatics could provide a valuable therapeutic target for ICH resolution. SummaryIn vivo awake imaging reveals the direct drainage of extravasated blood-solutes from brain parenchyma into dorsal meningeal lymphatic vessels, following focal or diffuse intracranial hemorrhage

neuroscience↗

bioRxiv2020

The role of the meningeal lymphatic system in local inflammation and trigeminal nociception implicated in migraine pain

BackgroundA system of lymphatic vessels has been recently characterized in the meninges, with a postulated role in cleaning the brain via cerebral fluid drainage. As meninges are the origin site of migraine pain, we hypothesized that malfunctioning of the lymphatic system should affect the local trigeminal nociception. To test this hypothesis, we studied nociceptive and inflammatory mechanisms in the meninges of K14-VEGFR3-Ig mice lacking the meningeal lymphatic system. MethodsWe recorded the spiking activity of meningeal afferents and estimated the local mast cells infiltration, calcitonin gene-related peptide (CGRP) and cytokine levels (basal and stimulated), as well as the dural trigeminal innervation in freshly-isolated hemiskull preparations from K14-VEGFR3-Ig (K14) or wild type C57BL/6 mice (WT). ResultsWe found that the meningeal level of CGRP and of the pro-inflammatory cytokines IL12-p70 and TNF (implicated in migraine) were reduced in the meninges of K14 mice. On the contrary, in the meninges of K14 mice, we found an increased level of the mast cell activator MCP-1 and, consistently, a larger number of dural mast cells. The other migraine-related pro-inflammatory cytokines did not differ between the two genotypes. The patterns of trigeminal innervation in meninges remained unchanged and we did not observe alterations in basal or ATP-induced nociceptive firing in the meningeal afferents. ConclusionsIn summary, the lack of meningeal lymphatic system does not induce migraine-like nociceptive state per se, but leads to a new balance between pro- and antiinflammatory factors implicated in migraine mechanisms.

neuroscience↗

bioRxiv2019

The CNS lymphatic system modulates the adaptive neuro-immune response in the perilesional cortex after brain trauma

RationaleThe recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous systems. The role of mLVs in modulating the neuro-immune response following a brain injury, however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after traumatic brain injury (TBI), suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified the subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of immune response in the brain after TBI. MethodsTBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI. ResultsIn both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, implying that mLVs are important in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate with alterations in peripheral circulating T cells, as assessed one month after injury induction. ConclusionsOur data support the hypothesis that mLVs are pivotal for a proper and specific neuro-immune response after TBI, which is principally mediated by the resident memory CD8+ T cells.

neuroscience↗