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

Authors: Wise-Faberowski, L  Robinson, PN  Rich, S  Warner, DS 
Citation: Wise-Faberowski L, etal., Anesth Analg. 2009 Jul;109(1):205-10.
Pubmed: (View Article at PubMed) PMID:19535712
DOI: Full-text: DOI:10.1213/ane.0b013e3181a27e37

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.

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CRRD Object Information
CRRD ID: 2325978
Created: 2010-06-16
Species: All species
Last Modified: 2010-06-16
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.