Meningothelial cell response under flow conditions
Meningothelial cells (MECs), also called leptomeningeal cells, are the cells that line the subarachnoid space (SAS) of the brain, spinal cord and optic nerve, covering not only the pia and arachnoid but also the intricate network of trabeculae that interconnect them. MECs cover the meninges in a mono-layer and are connected via tight junctions, gap junctions and desmosomes.They have been shown to not only provide coverage of the neuronal tissue but also to play an active role in the maintenance of homeostasis and to be actively involved in physiological and pathophysiological processes in the SAS. In particular, MECs were shown to influence SAS architecture during glaucomatous neurodegeneration. They also play an active role in the regulation of the cerebrospinal fluid (CSF) composition via the production of cytokines and proteins and the endocytosis of macro-molecules and apoptotic cells. Exposing MECs to elevated pressure induces cell proliferation and a dramatic decrease in endocytotic activity. These changes can be expected to directly impact SAS geometry, CSF composition and flow, all of which may in turn influence neuronal function. Based on their similarity to vascular endothelial cells, MECs might also be expected to respond to the shear forces imposed by the CSF flow or actively participate to waste clearance via trans-cellular transport. Yet, MECs are still largely unexplored, and their behavior under physiological and pathological conditions is not well understood. While prior experiments have investigated the response under different pressure levels, we will here assess the impact of shear stresses.
Based on former computational and MRI measurements, wall shear stresses induced by the cerebrospinal fluid flow in the SAS were estimated to range between 2 to 50 mPa. It has been hypothesized that, in glaucomatus or papilloedma patients, interruption of CSF along the optic SAS might be responsible for the subsequent damage to the optic nerve via a dis-regulation of MECs activity. Accordingly, we will characterize MECs response under varying flow and no flow conditions. Cell response characterization includes but, is not limited to, determining MEC proliferation, uptake of apoptotic cells, cytokine secretion, and trans-cellular transport. If phenotypical changes are observed, further examination will include preparation for phosphokinase arrays and gene expression assays in an effort to get insights into the underlying cell response mechanism.
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