Biofluid Biomarkers of Neuronal and Glial Injury in Epilepsy and Seizures: A Comprehensive Review

Epilepsy is one of the most common chronic neurological disorders worldwide, affecting millions of individuals and imposing a substantial cognitive, psychological, social, and economic burden. Despite significant advances in epilepsy research, key questions remain unresolved regarding the mechanisms underlying drug resistance, cognitive impairment, depression, and sudden unexpected death in epilepsy, as well as the contribution of recurrent seizures in promoting neuronal and glial injury. Addressing these challenges requires reliable biomarkers capable of accurately reflecting disease activity and detecting ongoing brain damage. In this review, we summarize the current evidence on biofluid biomarkers of neuronal and glial damage in epilepsy and seizures and discuss their potential clinical relevance. Particular attention is given to biomarkers associated with major pathways involved in epileptogenesis, including neuroinflammation, oxidative stress, neurodegeneration, blood–brain barrier disruption, altered gene expression, and synaptic remodeling. Emerging evidence suggests that circulating and cerebrospinal fluid biomarkers may provide valuable insights into seizure-related brain injury and the molecular mechanisms underlying epilepsy. Although none of these markers has yet been adopted in routine clinical practice, they represent promising tools for improving diagnosis, prognostic assessment, patient stratification, and the development of more personalized therapeutic strategies.