miR-146a and epilepsy: Expression profiles and target genes

Epilepsy ranks among the most prevalent neurological disorders, characterized by recurrent seizures and associated cognitive, psychological, and social consequences. Its complex and not fully understood pathophysiology resulting in diverse treatment strategies. Neuroinflammatory processes play a crucial role in the development of epilepsy and are modulated by microRNA (miRNA), which are the key regulators of genes associated with epileptogenesis. miR-146a stands out as a miRNA that may serve as a predictor of epileptogenesis. This study aimed to review the expression of miR-146a and its target genes in human and animal models with epilepsy across different tissues and experimental conditions. This systematic review was conducted following PRISMA guideline with a comprehensive literature search performed in PubMed, Scopus, and Google Scholar. Studies involving human subjects or animal models were considered, and all articles had to be published in English. Eligible studies must be primary research articles reporting in vivo or ex vivo data. Studies must provide quantitative or qualitative information on miR-146a expression or regulation, specifically focusing on epilepsy or seizure-related conditions. For animal model studies, seizure induction using pilocarpine hydrochloride or kainic acid is required. From a total of 4,142 studies obtained during the search, 20 studies were included in the review, comprising 12 human studies and eight animal studies. miR-146a is consistently upregulated in epilepsy, with elevated levels observed in patient blood, plasma, and brain tissue, and in hippocampal and cortical regions of animal models after status epilepticus. Increased miR-146a correlated with inflammation, seizure severity, and drug resistance. Changes in the expression and genetic variation of miR-146a, such as single-nucleotide polymorphism (SNP) are associated with poor neuronal function, susceptibility to seizure, and drug-resistance. This study highlights miR-146a's role in regulating neuroinflammation and its potential as a promising biomarker to improve diagnostic accuracy and guide innovative treatment strategies for epilepsy, ultimately benefiting patient outcomes. Further research is required to clarify the function of miR-146a across different types of epilepsy.