Cellular and Molecular Neurobiology
Author: Milton Paúl Márquez Cadena | Email: mpaulmarquezcadena@fmed.uba.ar
Milton Paúl Márquez Cadena1°, Dante Gomez Cuautle1°, Alicia Rossi1°, Alberto Javier Ramos1°
1° IBCN UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires
The hyperthermic seizure model in perinatal rats reflects the natural history of human temporal lobe epilepsy (TLE), showing significant changes in neuronal, glial, and peripheral immune systems and a decreased epilepsy threshold in adulthood. Despite these findings, the cellular astroglial role in the epileptogenesis remains unclear. Here, we analyzed the astroglial response in two paradigms (in vitro and in vivo). Initially, rat pups (10 days old) were exposed to elevated body temperatures (39-42°C) to induce hyperthermic seizures (HS), and brains were collected at 35 days post-HS. In vitro, primary astrocytes were exposed at 40°C for 6 hours to mimic similar heat-exposure conditions and then were studied by immunocytochemistry and qPCR. Our results showed that 35DPHS animals showed reactive gliosis with increased GFAP expression and a reduced epileptic threshold when treated with subconvulsive doses of pilocarpine (10 mg/kg). This contrasts with the absence of reactive gliosis, non-significative changes in proinflammatory cytokines IL1B, IL6, TNFa, and reduced GFAP expression observed in hyperthermia-exposed in vitro cultured astrocytes. We conclude that reactive gliosis and neuroinflammation observed in the rats subjected to hyperthermic seizures occur due to seizures rather than being a consequence of hyperthermia. This suggests that seizures, rather than hyperthermia, may be the initiating factor for epileptogenesis. Grants PICT 2021-0760, PIP CONICET, UBACYT