Biphasic edema after hypoxic-ischemic brain injury in neonatal rats reflects early neuronal and late glial damage

Pediatr Res. 1999 Sep;46(3):297-304. doi: 10.1203/00006450-199909000-00008.


Magnetic resonance imaging with diffusion- and T2-weighted imaging and 31P magnetic resonance spectroscopy was used to investigate the relationship between development of brain edema and alterations of the brain energy metabolism after hypoxia-ischemia (HI) brain injury in 7-d-old rats. The results were correlated with histologic examinations at various times during recovery up to 5 d. Moderate HI, induced by right common carotid artery ligation and subsequent exposure to 8% O2 for 90 min, produced a cytotoxic edema of 52+/-9% brain volume and depressed the ratio of phosphocreatine to inorganic phosphate from 1.43+/-0.21 to 0.11+/-0.09. Within 1 h of reoxygenation, the edema decreased to 4+/-2% of brain volume, demarcating the core of the lesion. At 5 h of recovery, a secondary cytotoxic edema together with a newly developing vasogenic edema expanded again, reaching its maximal extent of 45+/-10% brain volume at around 24 h. The ratio of phosphocreatine to inorganic phosphate recovered slowly, reaching 1.12+/-0.27 around 13 h. Thereafter it declined again in a manner analogous to the observations made in human newborns after severe perinatal asphyxia, reaching trough values of 0.48+/-0.22 around 24 h after HI. At the cellular level, the vast majority of neuronal death occurred before 15 h. Subsequently, strong glial activation lasted 2-3 d after HI. At 5 d, a cystic infarction of 35+/-12% brain volume was found. We conclude that the biphasic evolution of brain edema and energy metabolism reflects early neuronal and late glial damage in response to moderate HI injury. Therefore, the secondary energy breakdown reflects glial activation and subsequent glial death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain Edema / etiology
  • Brain Edema / metabolism
  • Brain Edema / pathology*
  • Brain Ischemia / complications*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Energy Metabolism*
  • Humans
  • Magnetic Resonance Imaging
  • Neuroglia / metabolism
  • Neuroglia / pathology*
  • Neurons / metabolism
  • Neurons / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors