naa a22 4500 510775896 CHVBK 20180411083230.0 cr unu---uuuuu 180411e20131201xx s 000 0 eng 10.1007/s12975-013-0275-0 doi (NATIONALLICENCE)springer-10.1007/s12975-013-0275-0 Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels [Elektronische Daten] [Melissa Laird, Pascaline Clerc, Brian Polster, Gary Fiskum] Mitochondrial respiratory capacity is critical for responding to changes in neuronal energy demand. One approach toward neuroprotection is the administration of alternative energy substrates ("biofuels”) to overcome brain injury-induced inhibition of glucose-based aerobic energy metabolism. This study tested the hypothesis that exogenous pyruvate, lactate, β-hydroxybutyrate, and acetyl-l-carnitine each increase neuronal respiratory capacity in vitro either in the absence of or following transient excitotoxic glutamate receptor stimulation. Compared to the presence of 5mM glucose alone, the addition of pyruvate, lactate, or β-hydroxybutyrate (1.0-10.0mM) to either day in vitro (DIV) 14 or 7 rat cortical neurons resulted in significant, dose-dependent stimulation of respiratory capacity, measured by cell respirometry as the maximal O2 consumption rate in the presence of the respiratory uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone. A 30-min exposure to 100μM glutamate impaired respiratory capacity for DIV 14, but not DIV 7, neurons. Glutamate reduced the respiratory capacity for DIV 14 neurons with glucose alone by 25% and also reduced respiratory capacity with glucose plus pyruvate, lactate, or β-hydroxybutyrate. However, respiratory capacity in glutamate-exposed neurons following pyruvate or β-hydroxybutyrate addition was still, at least, as high as that obtained with glucose alone in the absence of glutamate exposure. These results support the interpretation that previously observed neuroprotection by exogenous pyruvate, lactate, or β-hydroxybutyrate is at least partially mediated by their preservation of neuronal respiratory capacity. Springer Science+Business Media New York, 2013 Excitotoxicity nationallicence Energy metabolism nationallicence Pyruvate nationallicence Lactate nationallicence β-Hydroxybutyrate nationallicence Acetyl- l -carnitine nationallicence Mitochondria nationallicence aCSF : Artificial cerebrospinal fluid nationallicence AMPA : 2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid nationallicence ALCAR : Acetyl-l-carnitine nationallicence ATP : Adenosine triphosphate nationallicence BHB : β-Hydroxybutyrate nationallicence CNQX : 6-Cyano-7-nitroquinoxaline-2,3-dione nationallicence DIV : Day in vitro nationallicence FCCP : Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone nationallicence MK801 : (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate nationallicence NMDA : N-methyl d-aspartate nationallicence OCR : Oxygen consumption rate nationallicence Laird Melissa Department of Anesthesiology and the Shock Trauma and Anesthesiology Research Center, School of Medicine, University of Maryland, 685 W. Baltimore St., Baltimore, MD 21201, USA aut Clerc Pascaline Department of Anesthesiology and the Shock Trauma and Anesthesiology Research Center, School of Medicine, University of Maryland, 685 W. Baltimore St., Baltimore, MD 21201, USA aut Polster Brian Department of Anesthesiology and the Shock Trauma and Anesthesiology Research Center, School of Medicine, University of Maryland, 685 W. Baltimore St., Baltimore, MD 21201, USA aut Fiskum Gary Department of Anesthesiology and the Shock Trauma and Anesthesiology Research Center, School of Medicine, University of Maryland, 685 W. Baltimore St., Baltimore, MD 21201, USA aut Translational Stroke Research Springer US; http://www.springer-ny.com 4/6(2013-12-01), 643-651 1868-4483 4:6<643 2013 4 12975 https://doi.org/10.1007/s12975-013-0275-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-013-0275-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Laird Melissa Department of Anesthesiology and the Shock Trauma and Anesthesiology Research Center, School of Medicine, University of Maryland, 685 W. Baltimore St., Baltimore, MD 21201, USA aut NATIONALLICENCE 700 1- Clerc Pascaline Department of Anesthesiology and the Shock Trauma and Anesthesiology Research Center, School of Medicine, University of Maryland, 685 W. Baltimore St., Baltimore, MD 21201, USA aut NATIONALLICENCE 700 1- Polster Brian Department of Anesthesiology and the Shock Trauma and Anesthesiology Research Center, School of Medicine, University of Maryland, 685 W. Baltimore St., Baltimore, MD 21201, USA aut NATIONALLICENCE 700 1- Fiskum Gary Department of Anesthesiology and the Shock Trauma and Anesthesiology Research Center, School of Medicine, University of Maryland, 685 W. Baltimore St., Baltimore, MD 21201, USA aut NATIONALLICENCE 773 0- Translational Stroke Research Springer US; http://www.springer-ny.com 4/6(2013-12-01), 643-651 1868-4483 4:6<643 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer