Seizure-mediated iron accumulation and dysregulated iron metabolism after status epilepticus and in temporal lobe epilepsy

• DOI: 10.1007/s00401-021-02348-6
• Publication Date: 2021-07-22T08:03:07Z
• Authors: Till S. Zimmer; Bastian David; Diede W. M. Broek...; Martin Schidlowski; Gabriele Ruffolo; Anatoly Korotkov; Nicole N. van der...; Peter C. van Rijen; Angelika Mühlebner; Wim van Hecke; Johannes C. Baayen; Sander Idema; Liesbeth François; Jonathan van Eyll; Stefanie Dedeurwa...; Helmut W. Kessels; Rainer Surges; Theodor Rüber; Jan A. Gorter; James D. Mills; Erwin A. van Vliet; Eleonora Aronica
• Keywords: Hippocampal sclerosis

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