injection ameliorates lipopolysaccharide-induced cognitive decline via relieving acute neuroinflammation and BBB damage and upregulating the BDNF-CREB pathway in mice.

CONTEXT

Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. injection is the normally preferred treatment in sepsis in clinical settings.

OBJECTIVE

This study evaluated the benefits and related mechanism of injection on post-sepsis cognitive impairment.

MATERIALS AND METHODS

C57BL/6J mice were divided into three groups: Control, LPS (2.5 mg/kg, i.p.), and LPS injection (5.0 mL/kg). The surviving mice from sepsis were injected with material named injection continuously for 13 days. Behavioural tests were first conducted to evaluate the benefits. Second, inflammatory cytokines secretion, BBB integrity, neurodegeneration, and protein expression was evaluated and .

RESULTS

Compared with the LPS group, mice in injection group exhibited shorter escape latency (34.6 s versus 24.5 s) in the Morris water maze test. Treatment with injection could reverse LPS-induced neuroinflammation in mice and BV2 cells. Continuous injection treatment not only prevented blood-brain barrier dysfunction, but also prevented neurodegeneration. Further molecular docking tests and western blot results reflected that the main constituents of injection could interact with TrkB (the estimated binding energy values were -7.0 to -5.0 kcal/mol) and upregulate the protein expression of BDNF/TrkB/CREB signalling pathway during the chronic stage in mice.

DISCUSSION

injection treatment could reduce neuroinflammation, reverse BBB dysfunction, prevent neurodegeneration, and upregulate BDNF-CREB pathway during LPS-induced sepsis, ultimately preventing the development of cognitive decline.

CONCLUSION

injection could be a potential preventive and therapeutic strategy for sepsis survivors in clinical settings.