In Vivo Longitudinal Mapping of Brain Iron Accumulation After Pilocarpine-Induced Status Epilepticus

Iron accumulations have been identified in resected tissue from patients with refractory temporal lobe epilepsy. These deposits are linked to ferroptosis, a form of nonapoptotic cell death in which iron catalyzes the formation of reactive oxygen species, leading to lipid peroxidation. Experimentally, this process has recently been associated with seizures based on the increased levels of specific markers (4-hydroxynonenal and malondialdehyde) in the brain and plasma. Quantitative susceptibility mapping (QSM) offers an opportunity to detect the iron accumulations in vivo. In this study, we investigated how pilocarpine-induced status epilepticus contributes to the generation of iron deposits in diverse cerebral regions and whether QSM can detect these deposits longitudinally. We scanned 14 animals (n = 10 experimental and n = 4 control) at five different time points (pre-status epilepticus induction and 1, 7, 14, 21 days postinduction) using QSM. We identified iron deposits in the caudate putamen, hippocampus, thalamus, and primary somatosensory cortex of experimental animals, which is consistent with histological findings. The initial size of the hippocampal iron deposits significantly increased over the following weeks. None of these effects was observed in the control animals. The presence of cerebral iron depositions in epilepsy-related brain structures suggests that they could be involved in the onset, development, and progression of spontaneous recurrent seizures. Furthermore, noninvasive, longitudinal in vivo mapping of brain iron deposits could be a potential imaging marker in neurological disorders such as epilepsy. Future experiments will be required to determine the origin of the iron and avoid its progressive accumulation.