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  Comparison of the Effects of Cyclosporin A on the Metabolism of Perfused Rat Brain Slices During Normoxia and Hypoxia

Serkova, N., Donohoe P, Gottschalk, S., Hainz C, Neumann CU, Bickler PE, Benet LZ, Leibfritz, D., & Christians, U. (2002). Comparison of the Effects of Cyclosporin A on the Metabolism of Perfused Rat Brain Slices During Normoxia and Hypoxia. Journal of Cerebral Blood Flow Metabolism, 22(3), 342–352. doi:10.1097/00004647-200203000-00012.

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Serkova, N, Autor
Donohoe P, Gottschalk, S1, Autor           
Hainz C, Neumann CU, Bickler PE, Benet LZ, Leibfritz, D, Autor
Christians, U, Autor
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1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              

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 Zusammenfassung: The authors evaluated and compared the metabolic effects of cyclosporin A in the rat brain during normoxia and hypoxia/reperfusion. Ex vivo 31P magnetic resonance spectroscopy experiments based on perfused rat brain slices showed that under normoxic conditions, 500 mug/L cyclosporin A significantly reduced mitochondrial energy metabolism (nucleotide triphosphate, 83 plusminus 9 of controls; phosphocreatine, 69 plusminus 9) by inhibition of the Krebs cycle (glutamate, 77 plusminus 5) and oxidative phosphorylation (NAD+, 65 plusminus 14) associated with an increased generation of reactive oxygen species (285 plusminus 78 of control). However, the same cyclosporin A concentration (500 mug/L) was found to be the most efficient concentration to inhibit the hypoxia-induced mitochondrial release of Ca2+ in primary rat hippocampal cells with cytosolic Ca2+ concentrations not significantly different from normoxic controls. Addition of 500 mug/L cyclosporin A to the perfusion medium protected high-energy phosphate metabolism (nucleotide triphosphate, 11 plusminus 15 of control vs. 35 plusminus 9 with 500 mug/L cyclosporin A) and the intracellular pH (6.2 plusminus 0.1 control vs. 6.6 plusminus 0.1 with cyclosporin A) in rat brain slices during 30 minutes of hypoxia. Results indicate that cyclosporin A simultaneously decreases and protects cell glucose and energy metabolism. Whether the overall effect was a reduction or protection of cell energy metabolism depended on the concentrations of both oxygen and cyclosporin A in the buffer solution.

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 Datum: 2002-03
 Publikationsstatus: Erschienen
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 Identifikatoren: URI: http://www.nature.com/jcbfm/journal/v22/n3/pdf/9591223a.pdf
DOI: 10.1097/00004647-200203000-00012
BibTex Citekey: SerkovaDGHNBBLC2002
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Titel: Journal of Cerebral Blood Flow Metabolism
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 22 (3) Artikelnummer: - Start- / Endseite: 342–352 Identifikator: -