NMDA blockade attenuates caspase-3 activation and DNA fragmentation after neonatal hypoxia-ischemia

Neuroreport. 2000 Sep 11;11(13):2833-6. doi: 10.1097/00001756-200009110-00002.

Abstract

The aim was to study the effects of an NMDA receptor antagonist on caspase-3 activation and DNA fragmentation after hypoxia-ischemia (HI) in 7-day-old rats. Animals were treated with vehicle or MK-801 (0.5 mg/kg) directly after HI and sacrificed 8, 24 or 72h later. MK-801 reduced injury (by 53%), cells positive for active caspase-3 (by 39%) and DNA fragmentation (by 79%) in the cerebral cortex. Furthermore, MK-801 significantly decreased caspase-3 activity, and Western blots revealed a tendency towards decreased proteolytic cleavage of the caspase-3 proform. The data imply that NMDA receptors are involved in the activation of apoptotic processes in the immature brain after HI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / injuries
  • Animals, Newborn / metabolism
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Asphyxia Neonatorum / drug therapy
  • Asphyxia Neonatorum / metabolism*
  • Asphyxia Neonatorum / physiopathology
  • Caspase 3
  • Caspases / metabolism*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • DNA Fragmentation / drug effects*
  • DNA Fragmentation / physiology
  • Dizocilpine Maleate / pharmacology*
  • Female
  • Humans
  • Hypoxia-Ischemia, Brain / drug therapy
  • Hypoxia-Ischemia, Brain / metabolism*
  • Hypoxia-Ischemia, Brain / physiopathology*
  • Infant, Newborn
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • CASP3 protein, human
  • Casp3 protein, rat
  • Caspase 3
  • Caspases