Astragalus injection ameliorate Lipopolysaccaride-induced mice cognitive decline via relieving acute neuroinflammation and BBB damage as well as up-regulating BDNF-CREB pathway in chronic stage

Abstract Background: Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. Although there are major concerns in the prevention, diagnosis and clinical management of sepsis, strategies for the prevention and treatment of related sequelae are still missing. Researches found that neuroinflammation, oxidative damage and vascular permeability are the main causes of brain damage during the systemic inflammation. Astragalus injection, with the function of regulating vascular endothelial function and immunity, is normally applied in viral myocarditis, viral enteritis, diabetic nephropathy and sepsis in clinical in China. However, it is unknown that whether it could ameliorate the post-sepsis cognitive impairment. Methods: In a LPS-induced mice model of sepsis, the protective effects of Astragalus injection on post-sepsis cognitive impairment was first evaluated. Then the influence of Astragalus injection on inflammatory cytokines secretion, BBB integrality and the expression of tight junction proteins in the acute sepsis stage were studied later. Followed by the neurodegeneration analysis and BDNF-CREB pathway evaluation in the chronic sepsis stage. What’s more, in vitro experiment was further conducted to assess the effects of Astragalus injection on inflammatory cytokines secretion in microglia (BV2 cells). Results: Novel object recognition and Morris water maze tests show that Lipopolysaccharide (LPS)-induced sepsis in mice cause a long-term consequence of cognitive behavioral deficits, while Astragalus injection (5ml/kg) could prevent the development of the above long-term cognitive decline. Mechanism studies show that Astragalus injection (5ml/kg) not only could reverse LPS induced-neuroinflammation in mice and Bv2 cells, but also could protect the blood brain barrier dysfunction in acute stage. In addition, golgi staining and western blotting assays show that Astragalus injection could further prevent the neurodegeneration and up-regulate the BDNF-CREB pathway during the chronic stage. Conclusions: Taken together, our data suggest that Astragalus injection could be a valuable therapy strategy for sepsis survivors in clinical, as it can produce protect effects on the post-sepsis cognitive impairment from many target spots and stages.