title: Oxygen and seizure dynamics: I. Experiments.
abstract: We utilized a novel ratiometric nanoquantum dot fluorescence resonance energy transfer (NQD-FRET) optical sensor to quantitatively measure oxygen dynamics from single cell microdomains during hypoxic episodes as well as during 4-aminopyridine (4-AP)-induced spontaneous seizure-like events in rat hippocampal slices. Coupling oxygen sensing with electrical recordings, we found the greatest reduction in the O2 concentration ([O2]) in the densely packed cell body stratum (st.) pyramidale layer of the CA1 and differential layer-specific O2 dynamics between the st. pyramidale and st. oriens layers. These hypoxic decrements occurred up to several seconds before seizure onset could be electrically measured extracellularly. Without 4-AP, we quantified a narrow range of [O2], similar to the endogenous hypoxia found before epileptiform activity, which permits a quiescent network to enter into a seizure-like state. We demonstrated layer-specific patterns of O2 utilization accompanying layer-specific neuronal interplay in seizure. None of the oxygen overshoot artifacts seen with polarographic measurement techniques were observed. We therefore conclude that endogenously generated hypoxia may be more than just a consequence of increased cellular excitability but an influential and critical factor for orchestrating network dynamics associated with epileptiform activity.
authors.affiliation: Center for Neural Engineering, The Pennsylvania State University, University Park, Pennsylvania; Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania;
authors.forename: Justin
authors.initials: J
authors.lastname: Ingram
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania; Nanjing National Laboratory of Microstructures, Nanjing University, Nanjing, China;
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Physics, Astronomy, and Computational Sciences, George Mason University, Fairfax, Virginia;
authors.forename: John R
authors.initials: JR
authors.lastname: Cressman
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas;
authors.forename: Anupam
authors.initials: A
authors.lastname: Hazra
authors.affiliation: Center for Neural Engineering, The Pennsylvania State University, University Park, Pennsylvania; Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania;
authors.forename: Yina
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Yong-Eun
authors.initials: YE
authors.lastname: Koo
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas;
authors.forename: Jokūbas
authors.initials: J
authors.lastname: Žiburkus
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Raoul
authors.initials: R
authors.lastname: Kopelman
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania;
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Center for Neural Engineering, The Pennsylvania State University, University Park, Pennsylvania; Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania; Departments of Neurosurgery and Physics, The Pennsylvania State University, University Park, Pennsylvania sschiff@psu.edu.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schiff
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D010100:Oxygen
keywords: FRET; epilepsy; hippocampus; hypoxia; preseizure state; seizure termination; sensors