title: Abnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy.
abstract: Seizure-driven brain damage in epilepsy accumulates over time, especially in the hippocampus, which can lead to sclerosis, cognitive decline, and death. Excitotoxicity is the prevalent model to explain ictal neurodegeneration. Current labeling technologies cannot distinguish between excitotoxicity and hypoxia, however, because they share common molecular mechanisms. This leaves open the possibility that undetected ischemic hypoxia, due to ictal blood flow restriction, could contribute to neurodegeneration previously ascribed to excitotoxicity. We tested this possibility with Confocal Laser Endomicroscopy (CLE) and novel stereological analyses in several models of epileptic mice. We found a higher number and magnitude of NG2+ mural-cell mediated capillary constrictions in the hippocampus of epileptic mice than in that of normal mice, in addition to spatial coupling between capillary constrictions and oxidative stressed neurons and neurodegeneration. These results reveal a role for hypoxia driven by capillary blood flow restriction in ictal neurodegeneration.
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|División de Neurociencias, Universidad Pablo de Olavide, Ctra. Utrera km. 1, 41013 Sevilla, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Leal-Campanario
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|Department of Neuroscience, University of Montreal, 900 Rue St-Denis, Montreal Quebec H2X 0A9, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Alarcon-Martinez
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|Universidade de Vigo, Campus Universitario Lagoas-Marcosende, 36310 Vigo, Spain.
authors.forename: Hector
authors.initials: H
authors.lastname: Rieiro
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|SUNY Downstate Medical Center, Depts of Ophthalmology, Neurology, and Physiology/Pharmacology, 450 Clarkson Ave, MSC 58 Brooklyn, NY 11203, USA.
authors.forename: Susana
authors.initials: S
authors.lastname: Martinez-Conde
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.
authors.forename: Tugba
authors.initials: T
authors.lastname: Alarcon-Martinez
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|Interdisciplinary Graduate Program in Neuroscience, Arizona State University, PO Box 874601, Tempe, AZ 85287-4601, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|University of Arizona, College of Medicine, 1501 N. Campbell Ave., PO Box 245017, Tucson, Arizona 85724, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: LaMee
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|Graduate School of Arts and Science, New York University, New York, NY 10012, USA.
authors.forename: Pamela J Osborn
authors.initials: PJ
authors.lastname: Popp
authors.affiliation: Sinq Systems Inc., 8070 Georgia Avenue, Silver Spring, MD 20910, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Calhoun
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|Departamento Teoria Señal y Comunicaciones, E.T.S. Ingenieros Telecomunicacion, Universidad Valladolid, 47011 Valladolid, Spain.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Arribas
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Schlegel
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|Mind, Brain, and Behavior Research Center, University of Granada, 18071 Granada, Spain.
authors.forename: Leandro L Di
authors.initials: LL
authors.lastname: Stasi
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|Departments of Pediatrics, Clinical Neurosciences, Physiology &Pharmacology, Alberta Children's Hospital, Research Institute, Cumming School of Medicine, University of Calgary, Canada.
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
authors.affiliation: Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, 124 W. Thomas RD, Suite 105, Phoenix, AZ 85013, USA.
authors.forename: Landon
authors.initials: L
authors.lastname: Inge
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|SUNY Downstate Medical Center, Depts of Ophthalmology, Neurology, and Physiology/Pharmacology, 450 Clarkson Ave, MSC 58 Brooklyn, NY 11203, USA.|Department of Neurology, Johns Hopkins University, 600 N Wolfe St., Baltimore, Maryland 21287, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Otero-Millan
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Treiman
authors.affiliation: Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.|SUNY Downstate Medical Center, Depts of Ophthalmology, Neurology, and Physiology/Pharmacology, 450 Clarkson Ave, MSC 58 Brooklyn, NY 11203, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Macknik
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D001783:Blood Flow Velocity; D002196:Capillaries / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006624:Hippocampus / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018613:Microscopy, Confocal; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4