Grape Seed Proanthocyanidin Extract (GSPE) Mitigates Preterm White Matter Injury in Mice Via Improving Mitochondrial...

Grape seed proanthocyanidins extract (GSPE) has demonstrated significant neuroprotective efficacy in various neurodevelopmental disorders, nevertheless its potential beneficial role in preterm white matter injury (PWMI) remains unclear. This study aims to evaluate the therapeutic potential of GSPE against PWMI and the underlying mechanisms. GSPE (20 mg/Kg) was taken orally by the mouse after PWMI modeling. The survival rate, incidence of macroscopic lesions, body weight change were calculated. The myelin damage was evaluated. Mitochondrial homeostasis‌ was detected in PWMI model mice and cultured oligodendrocyte precursor cells (OPCs). Brain tissues from mice groups underwent RNA-seq. A dual-luciferase reporter assay was employed to validate the direct binding interaction between miR-153 and IMMP2L mRNA. The results showed that treatment of GSPE ameliorated cerebral ischemic injury in PWMI mice and improved behaviour ability and cognition deficits. GSPE restored mitochondria homeostasis in both PWMI mice and OPCs. Additionally, IMMP2L was found to be increased, while ROS was diminished by GSPE intervention. KEGG analysis showed that Wnt signaling pathway, the downstream of IMMP2L, changed significantly in PWMI group, while GSPE reversed it. The dual-luciferase reporter assay demonstrated that miR-153-3p directly suppressed IMMP2L expression through these binding sites. In summary, our findings revealed that GSPE treatment alleviated PWMI and restored mitochondrial homeostasis in mice.These beneficial effects are likely be attributed to the improvement of the activity of IMMP2L-related signaling pathways by GSPE.