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

Overview

Journal Cell Mol Neurobiol

Publisher Springer

Specialties Cell Biology
Molecular Biology
Neurology

Date 2009 Mar 5

PMID 19259807

Citations 17

Authors

David Nagy

Mate Marosi

Zsolt Kis

Tamas Farkas

Gabriella Rakos

Laszlo Vecsei

Vivian I Teichberg

Jozsef Toldi

Affiliations

Soon will be listed here.

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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References

Liu X, Branston N, Kawauchi M, Jellinek D, Symon L . Electrical stimulation of motor cortex in experimental cortical ischaemia: pyramidal responses at C5 and the surface EMG. Electroencephalogr Clin Neurophysiol. 1992; 85(3):209-14. DOI: 10.1016/0168-5597(92)90134-w. View

Stieg P, Sathi S, Warach S, Le D, Lipton S . Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat. Eur J Pharmacol. 1999; 375(1-3):115-20. DOI: 10.1016/s0014-2999(99)00214-9. View

Paxinos G, Watson C, Emson P . AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. J Neurosci Methods. 1980; 3(2):129-49. DOI: 10.1016/0165-0270(80)90021-7. View

Lye R, Slater P, Latham A . Rat middle cerebral artery occlusion: use of evoked potentials and tetrazolium staining to assess chronic ischaemia. J Neurosci Methods. 1987; 22(2):133-9. DOI: 10.1016/0165-0270(87)90007-0. View

Spreux-Varoquaux O, Bensimon G, Lacomblez L, Salachas F, Pradat P, Le Forestier N . Glutamate levels in cerebrospinal fluid in amyotrophic lateral sclerosis: a reappraisal using a new HPLC method with coulometric detection in a large cohort of patients. J Neurol Sci. 2002; 193(2):73-8. DOI: 10.1016/s0022-510x(01)00661-x. View

Bullock R, Zauner A, Woodward J, Myseros J, Choi S, Ward J . Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg. 1998; 89(4):507-18. DOI: 10.3171/jns.1998.89.4.0507. View

Toldi J, Farkas T, Perge J, Wolff J . Facial nerve injury produces a latent somatosensory input through recruitment of the motor cortex in the rat. Neuroreport. 1999; 10(10):2143-7. DOI: 10.1097/00001756-199907130-00027. View

Wright A, Hawkins C, Davies M . Photo-oxidation of cells generates long-lived intracellular protein peroxides. Free Radic Biol Med. 2003; 34(6):637-47. DOI: 10.1016/s0891-5849(02)01361-8. View

Zlotnik A, Gurevich B, Cherniavsky E, Tkachov S, Matuzani-Ruban A, Leon A . The contribution of the blood glutamate scavenging activity of pyruvate to its neuroprotective properties in a rat model of closed head injury. Neurochem Res. 2007; 33(6):1044-50. DOI: 10.1007/s11064-007-9548-x. View

10.

Choi D, Rothman S . The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci. 1990; 13:171-82. DOI: 10.1146/annurev.ne.13.030190.001131. View

11.

Castillo J, Davalos A, Naveiro J, Noya M . Neuroexcitatory amino acids and their relation to infarct size and neurological deficit in ischemic stroke. Stroke. 1996; 27(6):1060-5. DOI: 10.1161/01.str.27.6.1060. View

12.

Gottlieb M, Wang Y, Teichberg V . Blood-mediated scavenging of cerebrospinal fluid glutamate. J Neurochem. 2003; 87(1):119-26. DOI: 10.1046/j.1471-4159.2003.01972.x. View

13.

Zlotnik A, Gurevich B, Tkachov S, Maoz I, Shapira Y, Teichberg V . Brain neuroprotection by scavenging blood glutamate. Exp Neurol. 2006; 203(1):213-20. DOI: 10.1016/j.expneurol.2006.08.021. View

14.

Mies G, Iijima T, Hossmann K . Correlation between peri-infarct DC shifts and ischaemic neuronal damage in rat. Neuroreport. 1993; 4(6):709-11. DOI: 10.1097/00001756-199306000-00027. View

15.

Bordi F, Pietra C, Ziviani L, Reggiani A . The glycine antagonist GV150526 protects somatosensory evoked potentials and reduces the infarct area in the MCAo model of focal ischemia in the rat. Exp Neurol. 1997; 145(2 Pt 1):425-33. DOI: 10.1006/exnr.1997.6442. View

16.

Molchanova S, Koobi P, Oja S, Saransaari P . Interstitial concentrations of amino acids in the rat striatum during global forebrain ischemia and potassium-evoked spreading depression. Neurochem Res. 2004; 29(8):1519-27. DOI: 10.1023/b:nere.0000029564.98905.5c. View

17.

Nagababu E, Rifkind J . Heme degradation by reactive oxygen species. Antioxid Redox Signal. 2004; 6(6):967-78. DOI: 10.1089/ars.2004.6.967. View

18.

Traystman R, Kirsch J, Koehler R . Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J Appl Physiol (1985). 1991; 71(4):1185-95. DOI: 10.1152/jappl.1991.71.4.1185. View

19.

Teichberg V, Cohen-Kashi-Malina K, Cooper I, Zlotnik A . Homeostasis of glutamate in brain fluids: an accelerated brain-to-blood efflux of excess glutamate is produced by blood glutamate scavenging and offers protection from neuropathologies. Neuroscience. 2008; 158(1):301-8. DOI: 10.1016/j.neuroscience.2008.02.075. View

20.

Castillo J, Davalos A, Noya M . Progression of ischaemic stroke and excitotoxic aminoacids. Lancet. 1997; 349(9045):79-83. DOI: 10.1016/S0140-6736(96)04453-4. View