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Modeling Posthemorrhagic Hydrocephalus of Prematurity in Rats
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Modeling Posthemorrhagic Hydrocephalus of Prematurity in Rats

Published on: March 28, 2025

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Extended Combined Neonatal Treatment With Erythropoietin Plus Melatonin Prevents Posthemorrhagic Hydrocephalus of

Shenandoah Robinson1, Fatu S Conteh1, Akosua Y Oppong1

  • 1Division of Pediatric Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.

Frontiers in Cellular Neuroscience
|October 16, 2018
PubMed

Insights

Posthemorrhagic hydrocephalus of prematurity (PHHP) is a challenge. A new rat model shows neonatal erythropoietin (EPO) plus melatonin (MLT) treatment can prevent PHHP's key features, offering a potential non-surgical therapy.

Area of Science:

  • Neonatal Neurology
  • Developmental Neuroscience
  • Pediatric Critical Care

Background:

  • Posthemorrhagic hydrocephalus of prematurity (PHHP) affects vulnerable preterm infants, often following intraventricular hemorrhage (IVH) and chorioamnionitis (CAM).
  • Current treatments for PHHP are primarily surgical, necessitating the development of non-surgical therapeutic strategies.
  • Preclinical models are crucial for understanding PHHP pathogenesis and testing novel interventions.

Purpose of the Study:

  • To establish a preclinical model of PHHP using combined prenatal CAM and postnatal IVH in rats.
  • To investigate the efficacy of neonatal systemic erythropoietin (EPO) plus melatonin (MLT) treatment in modulating PHHP development.
  • To assess the impact of EPO+MLT on macrocephaly, ventriculomegaly, neurodevelopment, and brain microstructure.

Main Methods:

  • Prenatal CAM induction followed by postnatal day 1 IVH in rat pups.
  • Systemic administration of EPO+MLT or vehicle from postnatal day 2 to 10.
  • Assessment of macrocephaly, ventriculomegaly (histology and MRI), cliff aversion behavior, ependymal cilia, YAP mRNA, GFAP expression, and diffusion tensor imaging (DTI).

Main Results:

  • The CAM-IVH model recapitulated progressive macrocephaly, ventriculomegaly, and impaired cliff aversion behavior.
  • Neonatal EPO+MLT treatment significantly prevented macrocephaly, reduced ventriculomegaly, and normalized cliff aversion performance.
  • EPO+MLT treatment preserved ependymal motile cilia, normalized YAP mRNA levels, reduced GFAP, and improved white matter microstructural integrity on DTI.

Conclusions:

  • Combined prenatal inflammation and early postnatal IVH in rats effectively models PHHP.
  • Neonatal systemic EPO+MLT administration represents a promising non-surgical therapeutic strategy for PHHP.
  • This preclinical study supports further investigation of EPO+MLT for preventing or treating PHHP in preterm infants.

Keywords:
cerebrospinal fluidchorioamnionitisciliadiffusion tensor imaging (DTI)intraventricular hemorrhage (IVH)neurorepairpretermventriculomegaly

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