BACKGROUND Epilepsy is a prevalent chronic neurological disorder affecting 50 million individuals globally,with temporal lobe epilepsy(TLE)being the most common form.Despite advances in antiepileptic drug development,...BACKGROUND Epilepsy is a prevalent chronic neurological disorder affecting 50 million individuals globally,with temporal lobe epilepsy(TLE)being the most common form.Despite advances in antiepileptic drug development,over 30%of patients suffer from drug-resistant epilepsy,which can lead to severe cognitive impairments and adverse psychosocial outcomes.AIM To explore the role of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-203 in the regulation of neuroinflammation in a mouse model of epilepsy,providing a theoretical basis for the development of targeted microRNA delivery therapies for drug-resistant epilepsy.METHODS Adult male C57BL/6 mice were divided into a control group and a TLE model of 30 mice each,and the TLE model group was established by injecting kainic acid.BMSCs were isolated from the mice,and exosomes were purified using ultracentrifugation.Exosomal miR-203 was identified and characterized using highthroughput sequencing and quantitative reverse-transcription polymerase chain reaction.The uptake of exosomes by hippocampal neurons and the subsequent effects on neuroinflammatory markers were assessed using in vitro cell culture models.RESULTS Exosomal miR-203 exhibited a significant upregulation in BMSCs derived from epileptic mice.In vitro investigations demonstrated the efficient internalization of these exosomes by hippocampal neurons,resulting in downregulation of suppressor of cytokine signaling 3 expression and activation of the nuclear factor kappaB pathway,ultimately leading to enhanced secretion of pro-inflammatory cytokines.CONCLUSION Our study identifies exosomal miR-203 as a key regulator of neuroinflammation in a mouse model of epilepsy.The findings suggest that targeting miR-203 may offer a novel therapeutic strategy for epilepsy by modulating the suppression of cytokine signaling 3/nuclear factor kappaB pathway,thus providing a potential avenue for the development of cell-free therapeutics.展开更多
文摘BACKGROUND Epilepsy is a prevalent chronic neurological disorder affecting 50 million individuals globally,with temporal lobe epilepsy(TLE)being the most common form.Despite advances in antiepileptic drug development,over 30%of patients suffer from drug-resistant epilepsy,which can lead to severe cognitive impairments and adverse psychosocial outcomes.AIM To explore the role of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-203 in the regulation of neuroinflammation in a mouse model of epilepsy,providing a theoretical basis for the development of targeted microRNA delivery therapies for drug-resistant epilepsy.METHODS Adult male C57BL/6 mice were divided into a control group and a TLE model of 30 mice each,and the TLE model group was established by injecting kainic acid.BMSCs were isolated from the mice,and exosomes were purified using ultracentrifugation.Exosomal miR-203 was identified and characterized using highthroughput sequencing and quantitative reverse-transcription polymerase chain reaction.The uptake of exosomes by hippocampal neurons and the subsequent effects on neuroinflammatory markers were assessed using in vitro cell culture models.RESULTS Exosomal miR-203 exhibited a significant upregulation in BMSCs derived from epileptic mice.In vitro investigations demonstrated the efficient internalization of these exosomes by hippocampal neurons,resulting in downregulation of suppressor of cytokine signaling 3 expression and activation of the nuclear factor kappaB pathway,ultimately leading to enhanced secretion of pro-inflammatory cytokines.CONCLUSION Our study identifies exosomal miR-203 as a key regulator of neuroinflammation in a mouse model of epilepsy.The findings suggest that targeting miR-203 may offer a novel therapeutic strategy for epilepsy by modulating the suppression of cytokine signaling 3/nuclear factor kappaB pathway,thus providing a potential avenue for the development of cell-free therapeutics.
