Abnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy
Popp, Pamela J. Osborn
Calhoun, Michael E.
Arribas, Juan I.
Schlegel, Alexander A.
Stasi, Leandro L. Di
Rho, Jong M.
Treiman, David M.
Macknik, Stephen L.
AffiliationUniv Arizona, Coll Med
MetadataShow full item record
PublisherNATURE PUBLISHING GROUP
CitationAbnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy 2017, 7:43276 Scientific Reports
Rights© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractSeizure-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.
VersionFinal published version
SponsorsAmerican Epilepsy Society; Arizona Biomedical Research Commission; Research to Prevent Blindness Inc.; National Science Foundation [0726113, 0852636, 1523614]; Barrow Neurological Foundation; Mrs Marian Rochelle award; Mrs Grace Welton award; Dignity Health SEED award; Research Preventing Blindness Foundation; Empire Innovator Scholar (New York State) funds; Office of the Assistant Secretary of Defense for Health Affairs [W81XWH-15-1-0138]; Spanish Ministry of Education; Fundacion Seneca - Agencia de Ciencia y Tecnologia de la Region de Murcia; Fundacion Ibercaja; Fundacion Pedro Barrie de la Maza; MEC-Fulbright Postdoctoral Fellowship program [PS-2010-0667]; NICHD; New York State Empire Innovation Program
- Neurodegeneration and Pathology in Epilepsy: Clinical and Basic Perspectives.
- Authors: Farrell JS, Wolff MD, Teskey GC
- Issue date: 2017
- Neuronal hyperexcitability and seizures are associated with changes in glial-neuronal interactions in the hippocampus of a mouse model of epilepsy with mental retardation.
- Authors: Melø T, Bigini P, Sonnewald U, Balosso S, Cagnotto A, Barbera S, Uboldi S, Vezzani A, Mennini T
- Issue date: 2010 Dec
- Effects of hypoxia-induced neonatal seizures on acute hippocampal injury and later-life seizure susceptibility and anxiety-related behavior in mice.
- Authors: Rodriguez-Alvarez N, Jimenez-Mateos EM, Dunleavy M, Waddington JL, Boylan GB, Henshall DC
- Issue date: 2015 Nov
- Chronic intermittent hypoxic preconditioning suppresses pilocarpine-induced seizures and associated hippocampal neurodegeneration.
- Authors: Zhen JL, Wang WP, Zhou JJ, Qu ZZ, Fang HB, Zhao RR, Lu Y, Wang HC, Zang HM
- Issue date: 2014 May 14
- Region-specific deletions of the glutamate transporter GLT1 differentially affect seizure activity and neurodegeneration in mice.
- Authors: Sugimoto J, Tanaka M, Sugiyama K, Ito Y, Aizawa H, Soma M, Shimizu T, Mitani A, Tanaka K
- Issue date: 2018 Apr