From genetic risk to functional recovery: emerging genomic biomarkers and neurorestorative strategies in ischemic stroke

Abstract Ischemic stroke remains one of the leading causes of mortality and long-term disability worldwide despite major advances in acute reperfusion therapies. Increasing evidence indicates that stroke is a complex multifactorial disorder resulting from interactions among genetic susceptibility, vascular risk factors, environmental exposures, and biological aging. Recent developments in genome-wide association studies (GWAS), next-generation sequencing (NGS), transcriptomics, and multi-omics technologies have expanded understanding of the molecular mechanisms underlying ischemic stroke. Numerous susceptibility loci involved in vascular integrity, inflammation, lipid metabolism, coagulation, and endothelial function have been identified, creating opportunities for precision-medicine research; however, most genomic risk-prediction approaches remain investigational rather than established components of routine stroke care. Advances in biomarker discovery have likewise identified promising candidates for diagnosis, risk stratification, and outcome prediction, but many remain in the discovery or validation stage. Beyond acute management, post-stroke recovery is influenced by neuroplasticity together with initial stroke severity, infarct location and volume, reperfusion, comorbidities, complications, and rehabilitation intensity. Neuroplasticity should therefore be considered an important mechanism of recovery rather than a single dominant determinant. Among emerging neurorestorative strategies, erythropoietin (EPO) has demonstrated neuroprotective and plasticity-related effects in experimental models and has been studied in humans; nevertheless, clinical evidence remains insufficient to establish EPO as a routine treatment, and recent clinical work remains exploratory. This review therefore distinguishes established clinical evidence from emerging, investigational, and preclinical evidence while examining recent advances in stroke genetics, genomic biomarkers, precision medicine, neuroplasticity, and EPO-mediated recovery.