Serum exosome-mediated expression of ITGAX in hippocampus as a novel mechanism of blood-brain barrier dysfunction in epilepsy

Abstract

Background Epilepsy is one of the most common chronic neurological diseases, of which up to one third of patients have drug-resistant epilepsy. Recently, there is increasing evidence that exosomes play a crucial role in the pathogenesis of neurological diseases. Based on the previous results of serum exosome proteomics, this study aims to explore the pathogenesis of epilepsy from the perspective of exosomes. Methods The protein ITGAX was identified in previous proteomic studies. Firstly, ITGAX adeno-associated virus was injected through tail vein and exosome inhibitor was intraperitoneally injected to intervene the content of ITGAX in peripheral circulation and serum exosomes respectively, and then the expression of ITGAX in hippocampus was detected after intervention, so as to confirm the relationship between exosomes and the pathogenesis of epilepsy from the perspective of protein. Then, the effects of ITGAX expression changes on seizure latency and blood-brain barrier were observed by ethology and the detection of the blood-brain barrier-related molecules by Western blotting and ELISA. Results The results showed that, for epilepsy model, the expression of ITGAX in serum exosomes and hippocampus were both up-regulated. After reducing the expression of ITGAX in peripheral circulation and exosomes in serum, the level of ITGAX in hippocampus also decreased correspondingly. Behavioral results showed that down-regulation of ITGAX expression in hippocampus could prolong the latency of seizures and ameliorate the damage of blood-brain barrier. Conclusions This study is the first to demonstrate that exosomes are involved in the pathogenesis of epilepsy from the perspective of the transport of exosomes from the peripheral circulation to the central nervous system, and it indicates that ITGAX is highly expressed in the hippocampus from peripheral serum into the central nervous system mediated by exosomes, and its involvement in epileptic seizure mechanism may be related to changes in the permeability of the blood-brain barrier.