INTRODUCTION: Epilepsy is a common disorder of the central nervous system (CNS), which manifests as recurrent episodes of brain dysfunction caused by large-scale synchronous abnormal discharges of neurons. Neuroinflammation is a pathological stimulation which plays a critical role in epileptogenesis. Thus, targeted therapies aimed at neuroinflammation offer promising new approaches on epilepsy. Recent findings indicate that members of the FGF family influence epilepsy regulation. However, the protective effects of exsosomes containing enhanced EGF and FGF on neuroinflammation following seizure during epileptogenesis remain underexplored.

AIM(S): To investigate the protection effect of EGF-FGF enhanced exsosomes on after seizure neuroinflammation.

METHOD(S): In this study, we applied engineering enhanced EGF and FGF expression 293T-exosome (EGF-FGF.Exos) as treatment agent to PTZ induced seizures mice models.

RESULTS: In PTZ seizure mice model, EGF-FGF.Exos exhibited strong inhibitory effect on microglial activation and regulated microglial polarization towards the M2 phenotype while suppressed M1 polarization. RT-qPCR results demonstrated that EGF-FGF.Exos reduced the mRNA expression of central pro-inflammatory factors IL-1β, IL-6, and TNF-α in the animal model. HE staining showed that EGF-FGF.Exos pretreatment prevented neuronal loss in both the CA1 and CA3 regions of the hippocampus. Further experiment demonstrated that the inhibitory effects of EGF-FGF.Exos on pro-inflammatory factor expression, microglial activation, and M1 polarization pre-activation is caused by inhibiting the NF-κB pathway, and this inhibitory effect on after-seizure inflammation was reversed by PMA (NF-κB pathway agonist).

CONCLUSIONS: In conclusion, this current study demonstrated that EGF-FGF enhancing exosomes (EGF-FGF.Exos) inhibit inflammatory responses in PTZ seizure mice model by suppressing NF-κB pathway.

FINANCIAL SUPPORT: This study was supported by an industry collaboratory grant from Suzhou Zhiheng Biotechnology Co.Ltd.