Immunomodulatory and neuroprotective effects of HEPPP in mice with status epilepticus 2259375
Epilepsy is a chronic neurological disorder marked by recurrent seizures caused by abnormal electrical discharges and neuronal hyperexcitability. Besides the neuroelectrical component, the active involvement of the immune system in the pathophysiology of this disease has been recognized. In this study, we evaluated whether DL-3-hydroxy-3-ethyl-3-phenylpropionamide (HEPP), an effective drug in refractory epilepsy, presents an immunomodulatory effect on microglia cells in a murine model of pentylenetetrazole (PTZ)-induced status epilepticus. Three groups of five C57BL/6 mice were formed: control, epileptic untreated, and epileptic treated with HEPP. The behavioral assessment was conducted using the Racine scale. Flow cytometry was used to analyze microglial activation, cytokine production, and cell infiltration. We corroborated that animals with status epilepticus showed a sustained progression towards severe convulsive stages. In contrast, those treated with HEPP showed a significant decrease in the mean score, indicating a strong anticonvulsant effect of the compound. At the cellular level, we found a significant increase in the proportion of activated microglial cells in the brains of status epilepticus animals, as well as increased infiltration of peripheral cells; these findings were attenuated in the HEPP-treated group, suggesting a neuroprotective effect. Likewise, we identified an increase in the expression of TNF-α, IL-6, and IL-4 cytokines in activated microglia of the group of mice with status epilepticus, while treatment with HEPP decreased the expression of these cytokines, although it did not favor a transition towards an anti-inflammatory phenotype type M2, given the lack of statistical significance in CD206 cells. Our findings suggest that HEPP not only modulates seizure activity but also provides immunomodulatory and neuroprotective effects, positioning itself as a promising therapeutic alternative for epilepsy associated with chronic inflammation. The National Polytechnic Institute of Mexico provides the SIP20253908, SIP20254383, and SIP20253809 grants for this research. Neuroimmunology (NEUR)