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.
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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