Neurochem Res. 2025 Dec 29;51(1):25. doi: 10.1007/s11064-025-04634-1.
ABSTRACT
This study aims to investigate the regulatory role and molecular mechanism of the LINC00968/miR-194-5p axis in secondary neurological injury after intracerebral hemorrhage (ICH). A rat ICH model was established by injecting collagenase IV. In vitro, PC12 cells were treated with hemin to mimic the ICH environment. RT-qPCR was used to detect the levels of LINC00968 and miR-194-5p. Assessment of cell proliferation and apoptosis was performed with the CCK-8 assay and flow cytometry. The levels of SOD, MDA, ROS, and inflammatory factors (IL-6, TNF-α, IL-10) were measured using commercially available detection kits. To assess neurological deficits, the mNSS, corner turn, and forelimb placement tests were employed. To evaluate brain edema, the dry-wet weight method was utilized. The direct binding between LINC00968 and miR-194-5p was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In both in vivo and in vitro ICH models, LINC00968 expression was significantly upregulated. Knockdown of LINC00968 significantly enhanced cell proliferation, inhibited apoptosis, and reduced oxidative stress and inflammation in vitro. In rats, it significantly improved neurological deficits and reduced brain edema. Mechanistically, LINC00968 acts as a competing endogenous RNA (ceRNA) that sponges miR-194-5p. Suppressing miR-194-5p eliminated the neuroprotection resulting from LINC00968 silencing. LINC00968 aggravates neurological deficits, neuroinflammation, and oxidative stress after ICH by competitively binding to miR-194-5p.
PMID:41460533 | DOI:10.1007/s11064-025-04634-1