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J Neuropathol Exp Neurol. 2018 Sep 1;77(9):803-813. doi: 10.1093/jnen/nly058.

Blood Exposure Causes Ventricular Zone Disruption and Glial Activation In Vitro.

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Department of Neurological Surgery, Washington University School of Medicine and the St. Louis Children's Hospital, St. Louis, Missouri.
Department of Medicine.
Department of Neuroscience.
Department of Pediatrics.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri.


Intraventricular hemorrhage (IVH) is the most common cause of pediatric hydrocephalus in North America but remains poorly understood. Cell junction-mediated ventricular zone (VZ) disruption and astrogliosis are associated with the pathogenesis of congenital, nonhemorrhagic hydrocephalus. Recently, our group demonstrated that VZ disruption is also present in preterm infants with IVH. On the basis of this observation, we hypothesized that blood triggers the loss of VZ cell junction integrity and related cytopathology. In order to test this hypothesis, we developed an in vitro model of IVH by applying syngeneic blood to cultured VZ cells obtained from newborn mice. Following blood treatment, cells were assayed for N-cadherin-dependent adherens junctions, ciliated ependymal cells, and markers of glial activation using immunohistochemistry and immunoblotting. After 24-48 hours of exposure to blood, VZ cell junctions were disrupted as determined by a significant reduction in N-cadherin expression (p < 0.05). This was also associated with significant decrease in multiciliated cells and increase in glial fibrillary acid protein-expressing cells (p < 0.05). These observations suggest that, in vitro, blood triggers VZ cell loss and glial activation in a pattern that mirrors the cytopathology of human IVH and supports the relevance of this in vitro model to define injury mechanisms.


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