Epileptogenesis After Stroke: Current Insights Into Molecular and Structural Mechanisms

Stroke is among the most common causes of acquired epilepsy in adults, and post-stroke epilepsy (PSE) is a substantial driver of long-term disability. Epileptogenesis after stroke is not a single event but a prolonged, multi-phase process in which structural injury (neuronal loss, gliosis, blood-brain barrier (BBB) dysfunction, and maladaptive synaptic remodeling) interacts with molecular programs, including excitotoxicity, inflammation, oxidative stress, and epigenetic reprogramming, to create a persistently hyperexcitable network. Recent advances in neuroimaging, electrophysiology, and molecular profiling have yielded a growing set of candidate biomarkers (lesion topology and volume, metabolic and microstructural imaging signatures, early electroencephalographic abnormalities, and blood or CSF-derived proteins and microRNAs). Although none has yet been validated for routine clinical use, a multimodal, longitudinal biomarker strategy could enable risk stratification and serve as a surrogate endpoint for anti-epileptogenic trials. Therapeutic development remains focused largely on seizure suppression, but anti-inflammatory, antioxidant, metabolic-epigenetic, mitochondrial, and neuromodulatory approaches demonstrate promise in preclinical and translational studies. A clearer understanding of how structural damage and molecular signaling interlock over time, paired with pragmatic biomarker frameworks, offers a path toward prevention that may reduce the burden of epilepsy after stroke.