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In vitro detection of oxygen and glucose deprivation-induced neurodegeneration and pharmacological neuroprotection based on hippocampal stratum pyramidale width

   Oz, Pinar; Saybasili, Hale

Ischemia is one of the most prominent risk factors of neurodegenerative diseases such as Alzheimer's disease. The effects of oxygen and glucose depletion in hippocampal tissue due to ischemia can be mimicked in vitro using the oxygen and glucose deprivation (OGD) model. In this study, we applied OGD on acute rat hippocampal slices in order to design an elementary yet quantitative histological technique that compares the neuroprotective effects of (L)-carnitine to known neuroprotectors, such as the N-methyl-D-aspartate (NMDA) receptor antagonist memantine and the gamma-aminobutyric acid (GABA)-B receptor agonist baclofen. The level of neurodegeneration and the efficiency of pharmacological applications were estimated via stratum pyramidale width measurements in CA1 and CA3 regions of Nissl-stained 200-mu m thick hippocampal slices. We demonstrated that (L)-carnitine is an effective pharmacological target against the neurodegeneration induced by in vitro ischemia in a narrow range of concentrations. Even though the effect of chemical neuroprotection was significant, full recovery was not achieved in the dose interval of 5-100 mu M. In addition to chemical applications, hypothermia was used as a physical neuroprotection against ischemia-related neurodegeneration. Our results showed that incubation of slices for 60 min at 4 degrees C provided the same level of neuroprotection as the most effective doses of memantine, baclofen, and (L)-carnitine. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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