White matter injury following fetal inflammatory response syndrome induced by chorioamnionitis and fetal sepsis: lessons from experimental ovine models

Early Hum Dev. 2012 Dec;88(12):931-6. doi: 10.1016/j.earlhumdev.2012.09.011. Epub 2012 Oct 15.

Abstract

Chorioamnionitis and fetal sepsis can induce a fetal inflammatory response syndrome (FIRS) which is closely related to the development of white matter injury in the fetal brain. Large epidemiological studies support the link between FIRS and fetal brain injury with a clear association between the presence of in utero inflammation and neurodevelopmental complications such as cerebral palsy, autism and cognitive impairments later in life. Translational animal models of chorioamnionitis and fetal sepsis are essential in understanding the underlying pathophysiological mechanisms of fetal brain injury after exposure to intra-uterine inflammation. Concerning this aspect, ovine models have high translational value since neurodevelopment in sheep closely resembles the human situation. In this article, we will review clinical and experimental evidence for the link between FIRS and white matter injury in the fetal brain. With respect to experimental findings, we will particularly focus on the lessons learned from ovine models of chorioamnionitis and fetal sepsis. We also highlight two key players implied in the pathophysiology of white matter injury after in utero exposure to inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Diseases / etiology*
  • Brain Diseases / physiopathology
  • Chorioamnionitis* / physiopathology
  • Disease Models, Animal
  • Female
  • Humans
  • Pregnancy
  • Pregnancy Complications, Infectious
  • Sheep, Domestic
  • Systemic Inflammatory Response Syndrome / complications*