Abstract
During an ischemic event, the well-regulated glutamate (Glu) homeostasis is disturbed, which gives rise to extremely high levels of this excitatory neurotransmitter in the brain tissues. It was earlier reported that the administration of oxaloacetate (OxAc) as a Glu scavenger reduces the Glu level in the brain by enhancing the brain-to-blood Glu efflux. Here, we studied the neuroprotective effect of OxAc administration in a new focal ischemic model in rats. Occlusion of the middle cerebral artery resulted in immediate reduction of the somatosensory-evoked responses (SERs), and the amplitudes remained at the reduced level throughout the whole ischemic period. On reperfusion, the SERs started to increase, but never reached the control level. OxAc proved to be protective, since the amplitudes started to recover even during the ischemia, and finally fully regained the control level. The findings of the histological measurements were in accordance with the electrophysiological data. After Fluoro Jade C staining, significantly fewer labeled cells were detected in the OxAc-treated group relative to the control. These results provide new evidence of the neuroprotective effect of OxAc against ischemic injury, which strengthens the likelihood of its future applicability as a novel neuroprotective agent for the treatment of ischemic stroke patients.
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Acknowledgments
We are grateful to David Durham for linguistic correction of the manuscript. This study was financially supported by grants from TÁMOP 4.2.2-A-11/KONV-2012-0052, OTKA K105077 and Hungarian Brain Research Program—Grant No. KTIA_13_NAP-A-III/9. This research was realized in the frames of TÁMOP 4.2.4. A/2-11-1-2012-0001 “National Excellence Program—Elaborating and operating an inland student and researcher personal support system”. The project was subsidized by the European Union and co-financed by the European Social Fund.
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Knapp, L., Gellért, L., Kocsis, K. et al. Neuroprotective Effect of Oxaloacetate in a Focal Brain Ischemic Model in the Rat. Cell Mol Neurobiol 35, 17–22 (2015). https://doi.org/10.1007/s10571-014-0064-7
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DOI: https://doi.org/10.1007/s10571-014-0064-7