Blood exposure causes ventricular zone disruption and glial activation in vitro

Leandro Castaneyra-Ruiz, Diego M. Morales, James P. McAllister, Steven L. Brody, Albert M. Isaacs, Jennifer M. Strahle, Sonika M. Dahiya, David D. Limbrick

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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-cadherindependent 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.

Original languageEnglish
Pages (from-to)803-813
Number of pages11
JournalJournal of neuropathology and experimental neurology
Volume77
Issue number9
DOIs
StatePublished - Jan 1 2018

Keywords

  • Ependyma
  • Hydrocephalus
  • Intraventricular hemorrhage
  • N-cadherin
  • Ventricular zone

Fingerprint Dive into the research topics of 'Blood exposure causes ventricular zone disruption and glial activation in vitro'. Together they form a unique fingerprint.

  • Cite this