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NEUROSURGICAL ANESTHESIOLOGY AND NEUROSCIENCE

Oxygen and Glucose Deprivation in an Organotypic Hippocampal Slice Model of the Developing Rat Brain: The Effects on N-Methyl-d-Aspartate Subunit Composition

Lisa Wise-Faberowski, MD^*, Prairie Neeley Robinson, MD^*, Sarah Rich, BS^*, and David S. Warner, MD

From the *The Children’s Hospital Pediatric Anesthesia Laboratory, Department of Anesthesiology, University of Colorado Health Sciences Center, Aurora, Colorado; and Departments of Anesthesiology, Neurobiology, and Surgery, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina.

Address correspondence and reprint requests to Lisa Wise-Faberowski, MD, The Children’s Hospital, Department of Anesthesiology, 13123 East 16th Ave., B090, Aurora, CO 80045. Address e-mail to lisa.faberowski{at}uchsc.edu.

Abstract

BACKGROUND: Oganotypic 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.