Ferroptosis: Cause or consequence of epileptogenesis?

FRANCO MOSCOVICZ; TABORDA, CLAUDIA; MARIA VICTORIA CERVO; NATALIA BORDA; ENES AKUYZ; ALBERTO LAZAROWSKI; JERONIMO AUZMENDI

HAMIDIYE

Congreso; HISCON. Hamidiye International Student Congress; 2022

Hamidiye International School of Medicine

Iron is a necessary element involved in cellular metabolism, energy generation, and organism growth. Iron plays a key role in oxidative stress, as well as in neuroinflammation and ferroptosis, a novel mechanism of programmed cell death.Several biomarkers of ferroptosis were described in the hippocampus of the patients with refractory epilepsy and animal models of seizures. But the ferroptosis contribution to the epileptogenesis prosses remains unelucidated.This work aimed to study the iron deposit profile during the silent period between Status Epilepticus (SE) induction and the onset of spontaneous recurrent seizures (SRS).SE was induced on Wistar rats with pilocarpine, a temporal lobe epilepsy protocol. Fifteen days after SE the rats were fixed, the brains were removed and cut into coronal sections. Iron deposits were determined using Perls' Prussian blue reaction.Contrary to expectations, we did not find hemosiderin deposits in the hippocampus, but we were able to discriminate two types of hemosiderin positive staining (punctate and cellular mark) in different regions:In the anteroposterior axis, we found marks in Caudate-Putamen, Anterior Striatum, Medial Thalamus, Hypothalamus, and Posteroventral Thalamus. In the most anterior regions, the iron deposits were found forming a weak punctate mark, while in the middle regions we observed a mix of punctate and cellular marks. On the other hand, in posterior regions the cellular mark was prevalent.Taken together these results suggest a spatiotemporal contribution of ferroptosis to the spread of the induced damage that may conclude in temporal regions recruitment before SRS onset.