Predictive Value of Abnormal Expression of miR-378a-3p in Elderly Stroke Patients for Cognitive Impairment After Stroke.

Abstract

BackgroundPost-stroke cognitive impairment (PSCI) plays an important role in recovery and quality of life in elderly stroke patients. MicroRNAs play critical roles in the pathophysiology of PSCI.PurposeThe expression of miR-378a-3p in elderly stroke patients and its potential as a predictive biomarker for PSCI was explored.MethodsSerum samples from elderly stroke patients were collected for RT-qPCR analysis to evaluate miR-378a-3p. The Montreal Cognitive Assessment (MoCA) was performed to assess cognitive function. An oxygen-glucose deprivation (OGD) model with HT22 neuronal cells was employed to simulate ischemic injury in vitro. Functional assays, including dual-luciferase reporter assays, evaluated the direct targeting of TLR8 by miR-378a-3p. Cell viability was measured after modulation of miR-378a-3p and TLR8 expression to elucidate their roles.ResultsThe downregulation of miR-378a-3p in stroke (n = 82) compared to controls (n = 50) was observed, as well as in PSCI patients (n = 40) compared with that in post-stroke cognitively normal (n = 42). ROC curve analysis identified the potential of miR-378a-3p as a diagnostic biomarker for stroke and PSCI, yielding an area under the ROC curve (AUC) of 0.9039 (sensitivity: 89.02%; specificity: 72.00%). It was correlated positively with MoCA scores. ROC curve analysis resulted in an AUC of 0.8092 (sensitivity: 52.50%; specificity: 95.24%) for miR-378a-3p in predicting PSCI. miR-378a-3p had potential to predict PSCI occurrence. Luciferase assays confirmed direct binding between miR-378a-3p and TLR8. Overexpressing miR-378a-3p enhanced cell survival under OGD conditions, which was reversed by overexpressing TLR8.ConclusionReduced circulating miR-378a-3p associated with cognitive decline post-stroke, by negatively regulating TLR8.