Non-coding RNA regulatory networks in post-stroke neuropsychiatric complications: Mechanisms, delivery strategies, and translational challenges

Post-stroke neuropsychiatric complications (PSNCs), including depression, anxiety, and cognitive impairment, remain major barriers to functional recovery in stroke survivors. Biologically, these complications arise from converging pathological processes, including inflammatory responses, metabolic disturbances, and neural network remodeling. Non-coding RNAs (ncRNAs) are post-transcriptional regulators increasingly implicated in the transition from stroke-induced injury to neuropsychiatric outcomes. Their regulatory roles are mediated in part through competing endogenous RNA (ceRNA) networks and extracellular vesicle (EV) -based intercellular communication. However, the heterogeneous mechanisms by which ncRNAs contribute to distinct PSNC subtypes, as well as their translational trajectories, have not been systematically delineated. This review integrates current evidence on ncRNA-mediated pathological mechanisms, emerging delivery strategies, and translational advances in PSNCs. Current evidence indicates that ncRNAs dynamically regulate mitochondrial homeostasis, neuroinflammation, synaptic plasticity, and neurogenesis, collectively shaping post-stroke emotional and cognitive trajectories. At the translational level, EV-based and engineered nanocarrier platforms are being explored to address blood-brain barrier delivery challenges, while circulating ncRNAs show potential as molecular readouts for patient stratification and treatment monitoring. Nonetheless, a critical evidence gap persists between preclinical models and clinical application, particularly regarding standardized detection, long-term safety, and scalable manufacturing. By linking intracellular regulatory networks with intercellular communication mechanisms and evaluating their translational readiness, this review provides a structured framework for advancing ncRNA research toward clinically testable strategies in post-stroke neuropsychiatric care.