Perinatal Hypoxic‐Ischemic Brain Injury Enhances Quisqualic Acid‐Stimulated Phosphoinositide Turnover

Chu‐Kuang ‐K Chen, Faye S. Silverstein, Stephen K. Fisher, Daniel Statman, Michael V. Johnston

Research output: Contribution to journalArticle

Abstract

Abstract: In an experimental model of perinatal hypoxic‐ischemic brain injury, we examined quisqualic acid (Quis)‐stimulated phosphoinositide (PPI) turnover in hippocampus and striatum. To produce a unilateral forebrain lesion in 7‐day‐old rat pups, the right carotid artery was ligated and animals were then exposed to moderate hypoxia (8% oxygen) for 2.5 h. Pups were killed 24 h later and Quis‐stimulated PPI turnover was assayed in tissue slices obtained from hippocampus and striatum, target regions for hypoxic‐ischemic injury. The glutamate agonist Quis (10‐4M) preferentially stimulated PPI hydrolysis in injured brain. In hippocampal slices of tissue derived from the right cerebral hemisphere, the addition of Quis stimulated accumulation of inositol phosphates by more than ninefold (1,053 ± 237% of basal, mean ± SEM, n = 9). In contrast, the addition of Quis stimulated accumulation of inositol phosphates by about fivefold in the contralateral hemisphere (588 ± 134%) and by about sixfold in controls (631 ± 177%, p < 0.005, comparison of ischemic tissue with control). In striatal tissue, the corresponding values were 801 ± 157%, 474 ± 89%, and 506 ± 115% (p < 0.05). In contrast, stimulation of PPI turnover elicited by the cho‐linergic agonist carbamoylcholine, (10‐4 or 10‐2M) was unaffected by hypoxia‐ischemia. The results suggest that prior exposure to hypoxia‐ischemia enhances coupling of excitatory amino acid receptors to phospholipase C activity. This activation may contribute to the pathogenesis of irreversible brain injury and/or to mechanisms of recovery.

Original languageEnglish (US)
Pages (from-to)353-359
Number of pages7
JournalJournal of Neurochemistry
Volume51
Issue number2
DOIs
StatePublished - Aug 1988

Keywords

  • Carbamoylcholine
  • Hippocampus
  • Hypoxia‐ischemia
  • Inositol phospholipids
  • Perinatal
  • Quisqualic acid
  • Striatum

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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