Identification of Blood-Brain Barrier Injury-Related Biomarkers in Cerebral Infarction Using Transcriptomic Analysis

Background: Cerebral infarction leads to blood-brain barrier (BBB) disruption, exacerbating brain injury through edema, inflammation, and neuronal death. Although BBB damage is a critical event in stroke pathology, the underlying molecular mechanisms and reliable biomarkers remain poorly understood. This study aimed to identify key biomarkers associated with BBB injury following cerebral infarction using an in vitro model and transcriptomic approaches. Human cerebral microvascular endothelial cells (hCMEC/D3) were subjected to oxygen-glucose deprivation (OGD) and OGD/reoxygenation (OGD/R) to simulate ischemic and reperfusion injury. Cell viability, inflammatory cytokines, LDH release, and angiogenesis were assessed. Transcriptomic sequencing, weighted gene co-expression network analysis (WGCNA), and random forest algorithms were employed to identify differentially expressed genes and key biomarkers. OGD treatment significantly increased IL-1β, IL-6, TNF-α, and LDH levels, which were partially reversed by OGD/R. Transcriptomic analysis identified 1229 and 800 differentially expressed genes respectively in OGD and OGD/R comparisons. Enrichment analysis highlighted ribosome, endoplasmic reticulum, and mitochondrial pathways. Six core genes were screened, including RPS7, RPL36A, RPS9, RSL24D1, RPL41, and OSTC, all of which were upregulated under OGD and normalized after reoxygenation. We identified novel ribosome-related genes as potential biomarkers of BBB injury in cerebral infarction. These findings enhance our understanding of BBB pathophysiology and offer new targets for diagnostic and therapeutic strategies in ischemic stroke.