Long-Lasting Astroglial Remodeling Following Hyperthermic Seizures During the Latency Period

Temporal Lobe Epilepsy (TLE) is the most common form of epilepsy in adulthood, and a significant proportion of patients report have suffered complex febrile seizures (cFS), during childhood. The period between cFS and TLE, known as the latency period is thought to involve epileptogenesis. Using a model of hyperthermic seizures (HS), we previously showed that at 15 days post-HS (DPHS), both sexes exhibited moderate reactive gliosis, while males showed an atypical astroglial distribution in the piriform cortex (PC), increased Iba1+ cells, and a more pronounced proinflammatory phenotype. Both sexes also showed decreased AQP4 and Kir4.1 mRNA expression, with AQP4 redistribution in the PC of males. Males further exhibited a lower seizure threshold following pilocarpine exposure at 39DPHS. Given these more pronounced alterations in males, we now asked whether they persist over time. For that purpose, male rat pups were exposed to elevated core temperatures (39–42°C) to induce seizures. Brain tissue was collected at 35DPHS for immunohistochemistry. We found mild persistent reactive astrogliosis in the PC, with a normalized astrocyte distribution, together with an increased number of S100B+ cells. A mild alteration in AQP4 expression was also observed, without significative alterations in neuronal survival as shown by the NeuN+ cell area. These findings suggest that HS induces long-lasting astroglial alterations that may contribute to epileptogenesis. Grants: UBACYT, PIP CONICET