Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis

María Montserrat Guerra, Roberto Henzi, Alexander Ortloff, Nicole Lichtin, Karin Vío, Antonio J. Jiménez, María Dolores Dominguez-Pinos, César González, Maria Clara Jara, Fernando Hinostroza, Sara Rodríguez, Maryoris Jara, Eduardo Ortega, Francisco Guerra, Deborah A. Sival, Wilfred F.A. Den Dunnen, José M. Pérez-Fígares, James P. McAllister, Conrad E. Johanson, Esteban M. Rodríguez

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 each). Our results suggest that abnormal expression of the intercellular junction proteins N-cadherin and connexin-43 in NSC leads to 1) disruption of the ventricular and subventricular zones, loss of NSCs and neural progenitor cells; and 2) abnormalities in neurogenesis such as periventricular heterotopias and abnormal neuroblast migration. In HTx rats, the disrupted NSC and progenitor cells are shed into the cerebrospinal fluid and can be grown into neurospheres that display intercellular junction abnormalities similar to those of NSC of the disrupted ventricular zone; nevertheless, they maintain their potential for differentiating into neurons and glia. These NSCs can be used to investigate cellular and molecular mechanisms underlying this condition, thereby opening the avenue for stem cell therapy.

Original languageEnglish
Pages (from-to)653-671
Number of pages19
JournalJournal of neuropathology and experimental neurology
Issue number7
StatePublished - Jul 29 2015


  • Cerebrospinal fluid
  • Congenital hydrocephalus
  • HTx rat
  • Human
  • Junction pathology
  • Neural stem cells
  • Neurospheres
  • Ventricular zone disruption


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