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Oxaloacetate Decreases the Infarct Size and Attenuates the Reduction in Evoked Responses after Photothrombotic Focal Ischemia in the Rat Cortex

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Abstract

A traumatic brain injury or a focal brain lesion is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) levels in the cerebrospinal and interstitial fluids. It has recently been demonstrated that this excess Glu in the brain can be eliminated into the blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging the blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to a photothrombotic lesion and treated them after the illumination with a single 30-min-long administration of OxAc (1.2 mg/100 g, i.v.). Following induction of the lesion, we measured the infarct size and the amplitudes of the somatosensory evoked potentials (SEPs) as recorded from the skull surface. The photothrombotic lesion resulted in appreciably decreased amplitudes of the evoked potentials, but OxAc administration significantly attenuated this reduction, and also the infarct size assessed histologically. We suggest that the neuroprotective effects of OxAc are due to its blood Glu-scavenging activity, which, by increasing the brain-to-blood Glu efflux, reduces the excess Glu responsible for the anatomical and functional correlates of the ischemia, as evaluated by electrophysiological evoked potential (EP) measurements.

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Abbreviations

Glu:

Glutamate

OxAc:

Oxaloacetate

EP:

Evoked potential

SEPs:

Somatosensory evoked potentials

SSI:

Somatosensory cortex

FJB:

Fluoro-Jade B

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Acknowledgments

This work was supported by the National Bureau of Research and Development (NKTH RET 08/2004), OTKA K75628, TéT SK-26/200, and GVOP-3.2.1-2004-04-0357/3.0. T.F. is a Bolyai Fellow of the Hungarian Academy of Sciences. V.I.T has received support from the Weizmann Institute Nella and Leon Benoziyo Center for Neurological Diseases.

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Authors and Affiliations

  1. Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, 6726, Szeged, Hungary

    David Nagy, Mate Marosi, Zsolt Kis, Tamas Farkas, Gabriella Rakos & Jozsef Toldi

  2. Department of Neurology, University of Szeged, Semmelweis u. 6, 6701, Szeged, Hungary

    Laszlo Vecsei

  3. Department of Neurobiology, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Vivian I. Teichberg

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  1. David Nagy
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  2. Mate Marosi
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  3. Zsolt Kis
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  4. Tamas Farkas
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  8. Jozsef Toldi
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Correspondence to Jozsef Toldi.

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Nagy, D., Marosi, M., Kis, Z. et al. Oxaloacetate Decreases the Infarct Size and Attenuates the Reduction in Evoked Responses after Photothrombotic Focal Ischemia in the Rat Cortex. Cell Mol Neurobiol 29, 827–835 (2009). https://doi.org/10.1007/s10571-009-9364-8

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