Neuronal injuries induced by perinatal hypoxic-ischemic insults are potentiated by prenatal exposure to lipopolysaccharide: animal model for perinatally acquired encephalopathy

Dev Neurosci. Mar-Aug 2005;27(2-4):134-42. doi: 10.1159/000085985.

Abstract

We developed an original rat model for neonatal brain lesions whereby we explored the sequential effects of infectious and hypoxic-ischemic aggressions. We investigated the influence of combined exposure to prenatal infection with neonatal hypoxic-ischemic insult. Infectious effect was produced by administrating lipopolysaccharide (LPS) intraperitoneally to pregnant rats starting on embryonic day 17. Hypoxia-ischemia (H/I) was induced in the pups at postnatal day 1 (P1) by ligature of the right common carotid artery followed by exposure to hypoxia (8% O(2)) for 3.5 h. Animals were randomized into four groups: (1) control group: pups born to mothers subjected to intraperitoneal saline injection; (2) LPS group: pups exposed in utero to LPS; (3) H/I group: pups exposed to postnatal hypoxia after ligation of the right carotid artery, and (4) H/I plus LPS group: in utero exposure to LPS followed by postnatal hypoxia after ligation of the right carotid artery. Neuropathological findings in pups examined at P3 and P8 showed that groups 2, 3, and 4 presented a pattern of neuronal injury similar to those characterized as 'selective neuronal necrosis' within the context of human perinatal encephalopathy. Neuronal cellular injuries were particularly seen in the neocortex, mainly in parasagittal areas. The extent of neuronal cell injury in the brain of rats exposed to postnatal H/I was significantly increased by antenatal exposure to LPS. This animal model provides an experimental means to explore the respective roles of anoxic and infectious components in the pathogenesis of perinatal brain lesions and consequent cerebral palsy.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain Diseases / etiology*
  • Brain Diseases / pathology
  • Carotid Arteries / surgery
  • Female
  • Hypoxia-Ischemia, Brain / complications*
  • Hypoxia-Ischemia, Brain / pathology
  • Ligation
  • Lipopolysaccharides / adverse effects*
  • Models, Animal*
  • Neurons / drug effects
  • Neurons / pathology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Inbred Lew

Substances

  • Lipopolysaccharides