Silencing Epileptic Storms: Targeting miRNA-lncRNA Crosstalk in Astrocytes and Microglia to Disarm Neuroinflammatory Triggers

Jing Meng¹Wen Luo²Nana Zhang¹Mingxing Yu²Yuxuan He¹Chunyan Chen²Haifeng Shu³Yu Liang^4*

• ¹University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China
• ²Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
• ³Southwest Jiaotong University, Chengdu, Sichuan Province, China
• ⁴Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, China

Epilepsy is a chronic neurological disorder characterized by abnormal synchronous discharges of neurons in the brain. It affects approximately 70 million people worldwide, and approximately 30% of patients are resistant to existing antiepileptic drugs. Repeated seizures can lead to neuronal damage, glial cell activation and neuroinflammation, creating a vicious cycle of seizures, inflammation, and neuronal damage. Recent studies have shown that microRNAs play a key role in the pathological process of epilepsy by regulating the phenotype, inflammatory response and metabolic function of astrocytes and microglia. In addition, long noncoding RNAs, as upstream regulators of miRNAs, influence miRNA function by acting as competitive endogenous RNAs, further regulating glial cell activation and inflammatory responses. This paper is the first to systematically elucidate the synergistic role of miRNAs and lncRNAs in epilepsy through glial cell polarization, metabolic imbalance and exosome-mediated transcellular communication, providing a theoretical framework for the development of multitargeted intervention strategies.