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Sci Rep. 2017 Feb 27;7:43276. doi: 10.1038/srep43276.

Abnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy.

Author information

1
Barrow Neurological Institute, 350 W Thomas Rd, Phoenix, AZ 85013, USA.
2
División de Neurociencias, Universidad Pablo de Olavide, Ctra. Utrera km. 1, 41013 Sevilla, Spain.
3
Department of Neuroscience, University of Montreal, 900 Rue St-Denis, Montreal Quebec H2X 0A9, Canada.
4
Universidade de Vigo, Campus Universitario Lagoas-Marcosende, 36310 Vigo, Spain.
5
SUNY Downstate Medical Center, Depts of Ophthalmology, Neurology, and Physiology/Pharmacology, 450 Clarkson Ave, MSC 58 Brooklyn, NY 11203, USA.
6
Interdisciplinary Graduate Program in Neuroscience, Arizona State University, PO Box 874601, Tempe, AZ 85287-4601, USA.
7
University of Arizona, College of Medicine, 1501 N. Campbell Ave., PO Box 245017, Tucson, Arizona 85724, USA.
8
Graduate School of Arts and Science, New York University, New York, NY 10012, USA.
9
Sinq Systems Inc., 8070 Georgia Avenue, Silver Spring, MD 20910, USA.
10
Departamento Teoria Señal y Comunicaciones, E.T.S. Ingenieros Telecomunicacion, Universidad Valladolid, 47011 Valladolid, Spain.
11
Mind, Brain, and Behavior Research Center, University of Granada, 18071 Granada, Spain.
12
Departments of Pediatrics, Clinical Neurosciences, Physiology &Pharmacology, Alberta Children's Hospital, Research Institute, Cumming School of Medicine, University of Calgary, Canada.
13
Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, 124 W. Thomas RD, Suite 105, Phoenix, AZ 85013, USA.
14
Department of Neurology, Johns Hopkins University, 600 N Wolfe St., Baltimore, Maryland 21287, USA.

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.

PMID:
28240297
PMCID:
PMC5327474
DOI:
10.1038/srep43276
[Indexed for MEDLINE]
Free PMC Article

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