Oxygen and glucose deprivation in an organotypic hippocampal slice model of the developing rat brain: the effects on N-methyl-D-aspartate subunit composition.

Published

Journal Article

BACKGROUND: Organotypic hippocampal slices (OHS) are commonly used to screen for neuroprotective effects of pharmacological agents relevant to pediatric brain injury. The importance of donor rat pup age and N-methyl-D-aspartate (NMDA) receptor subunit composition have not been addressed. In this study, we evaluated the age-dependent effect of oxygen-glucose deprivation (OGD) in the developing rat brain and determined whether OGD modulates the NMDA receptor subunit composition. METHODS: OHS were prepared from rat pups on postnatal days (PND) 4, 7, 14, and 21 and cultured 7 days in vitro. The slices were exposed to OGD for durations of 5-60 min. After 24 and 72 h, OHS survival and NMDA subunit composition were assessed. RESULTS: Cell death was evident in OHS prepared from PND 14 and 21 rat pups (P < 0.001) with OGD durations of 5 and 10 min, respectively. In OHS prepared from PND7 rat pups, neurodegeneration was not evident until 20 min OGD (P < 0.001). Exposure to OGD in OHS prepared from PND4 and PND7 rat pups was associated with a transition in the NMDA receptor subunit composition from NR2B predominant to NR2A predominant subunit composition. CONCLUSIONS: This in vitro neonatal rat pup investigation using OHS supports both an age and an NMDA receptor subunit composition-dependent relationship between OGD and neuronal cell death.

Full Text

Duke Authors

Cited Authors

  • Wise-Faberowski, L; Robinson, PN; Rich, S; Warner, DS

Published Date

  • July 2009

Published In

Volume / Issue

  • 109 / 1

Start / End Page

  • 205 - 210

PubMed ID

  • 19535712

Pubmed Central ID

  • 19535712

Electronic International Standard Serial Number (EISSN)

  • 1526-7598

Digital Object Identifier (DOI)

  • 10.1213/ane.0b013e3181a27e37

Language

  • eng

Conference Location

  • United States