Compound porcine cerebroside and ganglioside injections improved anxiety and cognitive dysfunction through the NF-κB pathway in cerebral ischemia-reperfusion injury

Abstract

Abstract Background Cerebral ischemia-reperfusion injury (CIRI) can cause hippocampal inflammation and apoptosis, resulting in anxiety and cognitive dysfunction. Compound porcine cerebroside and ganglioside injections (CPCGI) are used to treat encephalopathy, but its therapeutic effects and mechanism require further exploration. Methods We screened key genes associated with the ischemic stroke (IS) and predicted their binding sites with CPCGI. We subsequently injected CPCGI into a middle cerebral artery occlusion (MCAO) rat model. 2,3,5-triphenyl tetrazolium chloride (TTC) staining and behavioral testing were performed. Hippocampal neuronal apoptosis was assessed by immunofluorescence. IL-1β, TNF-α, and NF-κB pathway were detected by Western blotting. Oxygen-glucose deprivation/reoxygenation (OGD/R)-HT-22 cells were treated CPCGI for 72 h. Cell viability and NF-κB were also evaluated. Results H2AC20, RPL3, RPL13A, RPL9, RPS23, and RPLP0 were identified as key IS genes. CPCGI was confirmed to interact with these proteins via molecular docking. Functional enrichment reflected the critical role of the NF-κB pathway in CIRI. Infarct volume and behavioral impairments in MCAO rats, especially anxiety and cognitive dysfunction, were improved by CPCGI in a dose-dependent manner. Immunofluorescence confirmed that hippocampal neuronal apoptosis was rescued by the CPCGI. Western blotting revealed that inflammation and NF-κB phosphorylation were inhibited. In vitro experiments showed that CPCGI increased the survival of OGD/R-HT-22 cells and inhibited phosphorylation of the NF-κB signaling pathway. Conclusion CPCGI can alleviate anxiety and cognitive dysfunction in CIRI and thus improve psychoneurological symptoms in patients with IS. We confirmed that CPCGI alleviate inflammation and apoptosis in the hippocampus by inhibiting the NF-κB signaling pathway.