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.

由于铁积累与活性氧 (ROS) 一起导致的神经元功能障碍可能是致癫痫过程的一个重要但未被充分认识的组成部分。然而，迄今为止，尚未详细讨论致癫痫脑中铁代谢的变化。在颞叶癫痫和海马硬化症 (TLE-HS) 患者的切除脑组织、癫痫持续状态 (SE) 后死亡患者的死后脑组织以及脑组织中研究了铁相关的神经病理学和抗氧化代谢过程。 TLE的电诱导SE大鼠模型。比较了三名局灶性癫痫患者在癫痫发作期间和之后的假定癫痫发作区的磁化率。最后，使用急性小鼠海马切片制剂和培养的人胎儿星形胶质细胞在体外研究了铁过载的细胞效应。虽然铁蓄积神经元具有固缩形态，但星形胶质细胞似乎获得了铁螯合能力，如 SE 或 TLE 患者海马中显着的铁蛋白表达和铁潴留所示。发作间期与发作后的比较显示癫痫患者癫痫发作区的磁化率增加。SE 后大鼠在急性期和慢性期（当自发复发性癫痫发作明显时）的海马铁水平始终较高。在体外，在暴露于铁的急性切片中，神经元很容易吸收铁，而诱发的癫痫样活动加剧了这种情况。用铁和 ROS 挑战的人类星形胶质细胞培养物增加了它们的抗氧化和铁结合能力，但同时在长期暴露后发展出促炎表型。这些数据表明，癫痫介导的慢性神经元铁摄取可能在 TLE-HS 的神经元功能障碍/丧失中起作用。另一方面，星形胶质细胞螯合铁，特别是在慢性癫痫中。该功能可能将星形胶质细胞转化为高度抗性的促炎表型，可能导致促癫痫炎症过程。特别是慢性癫痫。该功能可能将星形胶质细胞转化为高度抗性的促炎表型，可能导致促癫痫炎症过程。特别是慢性癫痫。该功能可能将星形胶质细胞转化为高度抗性的促炎表型，可能导致促癫痫炎症过程。