Astrocytic demise in the developing rat and human brain after hypoxic-ischemic damage

Dev Neurosci. 2009;31(5):459-70. doi: 10.1159/000232564. Epub 2009 Aug 11.

Abstract

In order to approach the physiopathological mechanism underlying the selective susceptibility of the immature brain to hypoxia-ischemia (HI), we have compared the lesions experimentally induced in postnatal day 7 rats using a model of neonatal stroke with those occurring in human fetal and neonatal brains. We first observed that gray and white matter lesions demonstrated a similar organization (core with cell loss and/or cavity and penumbra) and evolutionary pattern between experimental and human HI lesions. We then observed that, in the intermediate white matter, GFAP- and vimentin-positive astrocytes exhibited clasmatodendrosis and represent a major cell population involved in cell death in human brains (56.3 and 67.9%, respectively). In rat brains, GFAP- and TUNEL-positive astrocytes were also highly vulnerable, increasing between 6 (31%) and 72 (58%) hours after ischemia. Together, these results indicate that astroglial dysfunction may play a critical role in determining the progress and outcome of acute hypoxic-ischemic injury particularly in the developing brain.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology
  • Cell Count
  • Female
  • Fetus
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / pathology*
  • Hypoxia-Ischemia, Brain / physiopathology
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Neurons / metabolism
  • Neurons / pathology*
  • Rats
  • Staining and Labeling
  • Vimentin / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Vimentin