Abstract
Quinolinic acid (QUIN) kills neurons by activation of NMDA receptors that are accessed via the extracellular fluid (ECF). In vivo microdialysis was employed to quantify the dynamics of ECF QUIN levels. [(13)C7]QUIN was perfused through the probe for in vivo calibration to accurately quantify ECF QUIN concentrations. Osmotic pumps infused [(2H)3]QUIN subcutaneously to quantify blood contributions to ECF and tissue levels. Local QUIN production rates and influx and efflux rates across the blood-brain barrier were calculated from the extraction fraction of [(13)C7]QUIN, probe geometry, tissue diffusion coefficients, the extracellular volume fraction, and [(2)H3]QUIN/QUIN ratios in blood and dialysates. In normal brain, 85% of ECF QUIN levels (110 nM) originated from blood, whereas 59% of tissue homogenate QUIN (130 pmol/g) originated from local de novo synthesis. During systemic immune activation (intraperitoneal injection of endotoxin), blood QUIN levels increased (10.2-fold) and caused a rise in homogenate (10.8-fold) and ECF (18.5-fold) QUIN levels with an increase in the proportions of QUIN derived from blood. During CNS inflammation (local infusion of endotoxin), increases in brain homogenate (246-fold) and ECF (66-fold) QUIN...Continue Reading
Citations
Jul 31, 1999·Journal of Neurochemistry·L A KoenneckeM P Heyes
Mar 8, 2000·Microbiology and Molecular Biology Reviews : MMBR·J M DunwellP J Gane
Jun 16, 2006·Journal of Neurotrauma·Jennifer R YatesAndrew R Blight
Jan 19, 2007·Journal of Neurochemistry·César A J RibeiroMoacir Wajner
Jun 28, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Erik Kwidzinski, Ingo Bechmann
Mar 11, 2020·Frontiers in Immunology·John R MoffettAryan M Namboodiri
Jul 21, 2001·Annals of the New York Academy of Sciences·T P Obrenovitch
Jul 19, 2002·Journal of Neurochemistry·Tomoyuki KitaS P Markey
Oct 14, 2004·Redox Report : Communications in Free Radical Research·Frantisek St'astnýAbel Santamaría
Dec 10, 2016·The Journal of Nutrition·John D Fernstrom
Jan 26, 2018·Open Biology·Dorin SadeEhud Gazit
Apr 27, 1999·Journal of Neurochemistry·P F MorrisonM P Heyes
Jul 10, 1998·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M P HeyesS P Markey
Oct 12, 1999·The American Journal of Physiology·P F MorrisonE H Oldfield
Jan 9, 2001·Journal of Neurochemistry·A PittalugaM Raiteri
Aug 3, 2007·Journal of Neuroscience Research·Elisa LucciniAnna Pittaluga
Nov 18, 2000·Journal of Neurochemistry·J Urenjak, T P Obrenovitch
Aug 5, 1999·Journal of Neurosurgery·R R LonserE H Oldfield
Mar 24, 2021·Cellular and Molecular Life Sciences : CMLS·Massimiliano GasparriniNadia Raffaelli
Oct 20, 2001·American Journal of Obstetrics and Gynecology·T NichollsD W Walker
Aug 11, 2000·Toxicon : Official Journal of the International Society on Toxinology·T W Stone
Aug 12, 1999·European Journal of Pharmacology·F Moroni
Mar 10, 2001·Progress in Neurobiology·T W Stone
Nov 28, 2006·Neuroscience Research·Patrícia Fernanda SchuckMoacir Wajner
Sep 16, 2008·Neuroscience·B W McCollN J Rothwell