BLOOD GOT TO RID THE BRAIN OF EXCESS GLUTAMATE: A NOVEL APPROACH TO THE TREATMENT OF HUMAN STROKE AND OF OTHER NEUROLOGICAL DISORDERS
Keywords:
brain diseases, glutamate, strokeAbstract
A number of brain diseases such as stroke are characterized by a deleterious role of the excess glutamate levels present in brain extracellular fluids. On the basis of the failure of glutamate receptor antagonists to deal with the excess glutamate in brain, we developed a completely novel neuroprotective approach in which the excess glutamate in brain fluids is eliminated using blood glutamate scavengers that increase the naturally-occuring brain-to blood glutamate efflux. Two papers of published in the Journal of Cerebral Blood Flow and Metabolism now fully prove this neuroprotective concept.
References
Glutamate receptors in pediatric tumors of the central nervous system / K. S. Brocke, C. Staufner, H. Luksch [et al.] // Cancer Biol Ther. – 2009. – № 9. – P. 455–468.
Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion / S. P. Butcher, R. Bullock, D. I. Graham, J. McCulloch // Stroke. – 2000. – № 21. – P. 1727–1733.
Blood levels of glutamate oxaloacetate transaminase are stronger associated with good outcome in acute ishcemic stroke than glutamate pyruvate transaminase / F. Campos, M. Rodriguez-Yanez, M. Castellanos [et al.] // Clin Sci. – 2011. – № 121. – P. 11–18.
Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study / F. Campos, T. Sobrino, P. Ramos-Cabrer [et al.] // J Cereb Blood Flow Metab. – 2011. – № 31. – P. 1378–1386.
High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke / F. Campos, M. Rodriguez-Yanez, M. Castellanos [et al.] // J Cereb Blood Flow Metab. – 2011. – № 31 (6). – P. 1387–1393.
Castillo J. Progression of ischaemic stroke and excitotoxic aminoacids / J. Castillo, A. Davalos, M. Noya // Lancet. – 1997. – № 349. – P. 79–83.
Effect of ischemia on the in vivo release of striatal dopamine, glutamate, and gammaaminobutyric acid studied by intracerebral microdialysis / M. Y. Globus, R. Busto, W. D. Dietrich [et al.] // J Neurochem. – 1988. – № 51. – P. 1455–1464.
Gottlieb M. Blood-mediated scavenging of cerebrospinal fluid glutamate / M. Gottlieb, Y. Wang, V. I. Teichberg // J Neurochem. – 2003. – № 87. – P. 119–126.
Real-time measurement of glutamate release from the ischemic penumbra of the rat cerebral cortex using a focal middle cerebral artery occlusion model / L. L. Guyot, F. G. Diaz, M. H. O’Regan [et al.] // Neurosci Lett. – 2001. – № 299. – P. 37–40.
Haas R. H. High-performance liquid chromatographic measurement of selected blood citric acid cycle intermediates / R. H. Haas, J. Breuer, M. Hammen // J Chromatogr. – 1988. – № 425. – P. 47–57.
Methodological quality of animal studies of neuroprotective agents currently in phase II/ III acute ischemic stroke trials / M. Philip, M. Benatar, M. Fisher, S. I. Savitz // Stroke. – 2009. – № 40. – P. 577–581.
Phillis J. W. Changes in extracellular amino acid neurotransmitters and purines during and fol-lowing ischemias of different durations in the rat cerebral cortex / J. W. Phillis, M. Smith-Barbour, M. H. O’Regan // Neurochem Int. – 1996. – № 29. – P. 115–120.
Expression of glutamate receptor subunits in human cancers / A. Stepulak, H. Luksch, C. Gebhardt [et al.] // Histochem Cell Biol. – 2009. – № 132. – P. 435–445.
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 neuropa-thologies / V. I. Teichberg, K. Cohen-Kashi-Malina, I. Cooper, A. Zlotnik // Neuroscience. – 2009. – № 158. – P. 301–308.
Tsai P. J. Circadian variations in plasma and erythrocyte glutamate concentrations in adult men consuming a diet with and without added monosodium glutamate / P. J. Tsai, P. C. Huang // J Nutr. – 2000. – № 130. – P. 1002–1004.
The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate / A. Zlotnik, S. E. Gruenbaum, A. A. Artru [et al.] // J Neurosurg Anesthesiol. – 2009. – № 21. – P. 235–241.
The contribution of the blood glutamate scavenging activity of pyruvate to its neuroprotective properties in a rat model of closed head injury / A. Zlotnik, B. Gurevich, E. Cherniavsky [et al.] // Neurochem Res. – 2008. – № 33. – P. 1044–1050.
Brain neuroprotection by scavenging blood glutamate / A. Zlotnik, B. Gurevich, S. Tkachov [et al.] // Exp Neurol. – 2007. – № 203. – P. 213–220.
