Cerium oxide nanoparticles alleviate sepsis-related cognitive impairments in rats

Abstract

Abstract Background This study aimed to investigate the therapeutic potential of cerium oxide nanoparticles (CeO2NPs) in sepsis-related cognitive impairments. Methods X-ray diffractometer and scanning electron microscopy were used to characterize the nanoparticles. Cecal ligation and puncture (CLP)-induced sepsis rat model was established. The rats were orally administered vehicle or different doses of CeO2NPs (4, 8, or 16 mg/kg) once daily for 7 days. Neurobehavioral assessment and Morris water maze test were carried out to evaluate the cognitive ability of the rats. The hippocampus and blood samples were collected at 7 days after treatment. ELISA was performed to measure the serum levels of proinflammatory cytokines and oxidative stress markers. Western blot analysis was conducted to determine the hippocampal expression of matrix metalloproteinases (MMPs). Results CeO2NPs were crystalline with diameters of approximately 30 nm. Compared with vehicle-treated septic rats, CeO2NPs-treated ones exhibited significantly increased neurobehavioral scores and survival rates, shortened escape latencies, increased numbers of platform crossings, as well as longer swimming paths and more time spent in the target quadrant. ELISA showed that CeO2NPs effectively reversed CLP-induced elevations in the serum levels of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and oxidative stress indicators (SOD and CAT). Furthermore, CeO2NPs strongly abolished CLP-induced upregulation of MMP-2 and MMP-9 protein expression related to blood-brain barrier disruption in the hippocampus of septic rats. Of note, all the effects of CeO2NPs were dose dependent. Conclusion CeO2NPs ameliorate cognitive ability and survival rate of septic rats possibly by alleviating systemic inflammation, oxidative stress, and blood-brain barrier disruption.