Journal Article

DZNE-2021-01505

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Seizure-mediated iron accumulation and dysregulated iron metabolism after status epilepticus and in temporal lobe epilepsy.

Zimmer, T. S. ; David, B. ; Broekaart, D. W. M. ; Schidlowski, M.DZNE* ; Ruffolo, G. ; Korotkov, A. ; van der Wel, N. N. ; van Rijen, P. C. ; Mühlebner, A. ; van Hecke, W. ; Baayen, J. C. ; Idema, S. ; François, L. ; van Eyll, J. ; Dedeurwaerdere, S. ; Kessels, H. W. ; Surges, R. ; Rüber, T. ; Gorter, J. A. ; Mills, J. D. ; van Vliet, E. A. ; Aronica, E.

2021
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00401-021-02348-6

Abstract: Neuronal dysfunction due to iron accumulation in conjunction with reactive oxygen species (ROS) could represent an important, yet underappreciated, component of the epileptogenic process. However, to date, alterations in iron metabolism in the epileptogenic brain have not been addressed in detail. Iron-related neuropathology and antioxidant metabolic processes were investigated in resected brain tissue from patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS), post-mortem brain tissue from patients who died after status epilepticus (SE) as well as brain tissue from the electrically induced SE rat model of TLE. Magnetic susceptibility of the presumed seizure-onset zone from three patients with focal epilepsy was compared during and after seizure activity. Finally, the cellular effects of iron overload were studied in vitro using an acute mouse hippocampal slice preparation and cultured human fetal astrocytes. While iron-accumulating neurons had a pyknotic morphology, astrocytes appeared to acquire iron-sequestrating capacity as indicated by prominent ferritin expression and iron retention in the hippocampus of patients with SE or TLE. Interictal to postictal comparison revealed increased magnetic susceptibility in the seizure-onset zone of epilepsy patients. Post-SE rats had consistently higher hippocampal iron levels during the acute and chronic phase (when spontaneous recurrent seizures are evident). In vitro, in acute slices that were exposed to iron, neurons readily took up iron, which was exacerbated by induced epileptiform activity. Human astrocyte cultures challenged with iron and ROS increased their antioxidant and iron-binding capacity, but simultaneously developed a pro-inflammatory phenotype upon chronic exposure. These data suggest that seizure-mediated, chronic neuronal iron uptake might play a role in neuronal dysfunction/loss in TLE-HS. On the other hand, astrocytes sequester iron, specifically in chronic epilepsy. This function might transform astrocytes into a highly resistant, pro-inflammatory phenotype potentially contributing to pro-epileptogenic inflammatory processes.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; Animals (MeSH) ; Astrocytes: metabolism (MeSH) ; Astrocytes: pathology (MeSH) ; Case-Control Studies (MeSH) ; Cell Culture Techniques (MeSH) ; Disease Models, Animal (MeSH) ; Epilepsy, Temporal Lobe: complications (MeSH) ; Epilepsy, Temporal Lobe: metabolism (MeSH) ; Epilepsy, Temporal Lobe: pathology (MeSH) ; Female (MeSH) ; Hippocampus: metabolism (MeSH) ; Humans (MeSH) ; Iron: metabolism (MeSH) ; Iron Metabolism Disorders: etiology (MeSH) ; Iron Metabolism Disorders: pathology (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Oxidative Stress: physiology (MeSH) ; Rats (MeSH) ; Status Epilepticus: complications (MeSH) ; Status Epilepticus: metabolism (MeSH) ; Status Epilepticus: pathology (MeSH) ; Astrocytes ; Glutathione metabolism ; Iron ; Status epilepticus ; Temporal lobe epilepsy with hippocampal sclerosis

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Contributing Institute(s):

1. MR Physics (AG Stöcker)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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