Neuron specific metabolic adaptations following multi-day exposures to oxygen glucose deprivation.

Zeiger SL, McKenzie JR, Stankowski JN, Martin JA, Cliffel DE, McLaughlin B
Biochim Biophys Acta. 2010 1802 (11): 1095-104

PMID: 20656023 · PMCID: PMC2943006 · DOI:10.1016/j.bbadis.2010.07.013

Prior exposure to sub toxic insults can induce a powerful endogenous neuroprotective program known as ischemic preconditioning. Current models typically rely on a single stress episode to induce neuroprotection whereas the clinical reality is that patients may experience multiple transient ischemic attacks (TIAs) prior to suffering a stroke. We sought to develop a neuron-enriched preconditioning model using multiple oxygen glucose deprivation (OGD) episodes to assess the endogenous protective mechanisms neurons implement at the metabolic and cellular level. We found that neurons exposed to a five minute period of glucose deprivation recovered oxygen utilization and lactate production using novel microphysiometry techniques. Using the non-toxic and energetically favorable five minute exposure, we developed a preconditioning paradigm where neurons are exposed to this brief OGD for three consecutive days. These cells experienced a 45% greater survival following an otherwise lethal event and exhibited a longer lasting window of protection in comparison to our previous in vitro preconditioning model using a single stress. As in other models, preconditioned cells exhibited mild caspase activation, an increase in oxidized proteins and a requirement for reactive oxygen species for neuroprotection. Heat shock protein 70 was upregulated during preconditioning, yet the majority of this protein was released extracellularly. We believe coupling this neuron-enriched multi-day model with microphysiometry will allow us to assess neuronal specific real-time metabolic adaptations necessary for preconditioning.

Copyright © 2010 Elsevier B.V. All rights reserved.

MeSH Terms (18)

Adaptation, Physiological Animals Blotting, Western Caspase 3 Cell Hypoxia Cells, Cultured Energy Metabolism Enzyme Activation Glucose HSP70 Heat-Shock Proteins Immunohistochemistry Neurons Oxygen Rats Rats, Sprague-Dawley Reactive Oxygen Species Stress, Physiological Time Factors

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