Clinical significance of lncRNA-miRNA axes in ischemic stroke: Diagnostic value, prognostic relevance, and therapeutic potential.

Ischemic stroke and subsequent reperfusion injury are major causes of mortality and long-term neurological disability, driven by complex mechanisms of excitotoxicity, oxidative stress, neuroinflammation, endothelial dysfunction, and blood-brain barrier disruption. Increasing evidence indicates that long non-coding RNA (lncRNA)-microRNA (miRNA) regulatory axes are central components of this pathobiology. Acting through competing endogenous RNA (ceRNA) mechanisms, lncRNAs sequester miRNAs and thereby modulate downstream messenger RNA expression. In turn, this mechanism affects critical pathways involved in neuronal apoptosis, autophagy, pyroptosis, angiogenesis, vascular remodeling, and post-ischemic repair. Depending on the molecular context, these networks can either amplify ischemic neurotoxicity or activate endogenous neuroprotective responses. From a diagnostic perspective, circulating lncRNA-miRNA signatures represent promising minimally invasive biomarkers because of their relative stability in peripheral blood and their close association with inflammatory, apoptotic, oxidative, and vascular injury pathways. Reported studies in acute ischemic stroke show moderate-to-excellent diagnostic performance, with some biomarker panels also distinguishing ischemic from hemorrhagic stroke. Bioinformatic and transcriptomic analyses further strengthen their clinical relevance by identifying stroke-associated ceRNA networks, prioritizing hub transcripts, and linking these signatures to immune activation, neuronal death, and vascular dysfunction. Therapeutically, these regulatory axes are increasingly viewed as potential molecular targets for RNA-based intervention, neuroprotection, and personalized medicine. Future progress will depend on integrating bioinformatics, spatial transcriptomics, nanodelivery systems, and artificial intelligence to refine mechanism-based diagnostics, prognostics, and targeted therapies in ischemic stroke.