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Anesth Analg. 2009 Jul;109(1):205-10. doi: 10.1213/ane.0b013e3181a27e37.

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

Author information

1
The Children's Hospital Pediatric Anesthesia Laboratory, Department of Anesthesiology, University of Colorado Health Sciences Center, Aurora, Colorado, USA. lisa.faberowski@uchsc.edu

Abstract

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.

PMID:
19535712
PMCID:
PMC4175416
DOI:
10.1213/ane.0b013e3181a27e37
[Indexed for MEDLINE]
Free PMC Article

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