Neonatal hydrocephalus leads to white matter neuroinflammation and injury in the corpus callosum of Ccdc39 hydrocephalic mice

Danielle S. Goulding, R. Caleb Vogel, Chirayu D. Pandya, Crystal Shula, John C. Gensel, Francesco T. Mangano, June Goto, Brandon A. Miller

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


OBJECTIVE The authors sought to determine if hydrocephalus caused a proinflammatory state within white matter as is seen in many other forms of neonatal brain injury. Common causes of hydrocephalus (such as trauma, infection, and hemorrhage) are inflammatory insults themselves and therefore confound understanding of how hydrocephalus itself affects neuroinflammation. Recently, a novel animal model of hydrocephalus due to a genetic mutation in the Ccdc39 gene has been developed in mice. In this model, ciliary dysfunction leads to early-onset ventriculomegaly, astrogliosis, and reduced myelination. Because this model of hydrocephalus is not caused by an antecedent proinflammatory insult, it was utilized to study the effect of hydrocephalus on inflammation within the white matter of the corpus callosum. METHODS A Meso Scale Discovery assay was used to measure levels of proinflammatory cytokines in whole brain from animals with and without hydrocephalus. Immunohistochemistry was used to measure macrophage activation and NG2 expression within the white matter of the corpus callosum in animals with and without hydrocephalus. RESULTS In this model of hydrocephalus, levels of cytokines throughout the brain revealed a more robust increase in classic proinflammatory cytokines (interleukin [IL]–1β, CXCL1) than in immunomodulatory cytokines (IL-10). Increased numbers of macrophages were found within the corpus callosum. These macrophages were polarized toward a proinflammatory phenotype as assessed by higher levels of CD86, a marker of proinflammatory macrophages, compared to CD206, a marker for antiinflammatory macrophages. There was extensive structural damage to the corpus callosum of animals with hydrocephalus, and an increase in NG2-positive cells. CONCLUSIONS Hydrocephalus without an antecedent proinflammatory insult induces inflammation and tissue injury in white matter. Future studies with this model will be useful to better understand the effects of hydrocephalus on neuroinflammation and progenitor cell development. Antiinflammatory therapy for diseases that cause hydrocephalus may be a powerful strategy to reduce tissue damage.

Original languageEnglish
Pages (from-to)476-483
Number of pages8
JournalJournal of Neurosurgery: Pediatrics
Issue number5
StatePublished - May 2020

Bibliographical note

Publisher Copyright:
©AANS 2020, except where prohibited by US copyright law


  • Corpus callosum
  • Hydrocephalus
  • Microglia
  • Myelin
  • Neuroinflammation

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology


Dive into the research topics of 'Neonatal hydrocephalus leads to white matter neuroinflammation and injury in the corpus callosum of Ccdc39 hydrocephalic mice'. Together they form a unique fingerprint.

Cite this