Targeting brain injury in sepsis: how remimazolam modulates the TLR4/NF-κB pathway in rats

Sepsis-associated brain injury can lead to severe neurobehavioral and cognitive impairments due to inflammation, oxidative stress, and blood-brain barrier (BBB) dysfunction. Remimazolam (RM), a novel benzodiazepine, may have therapeutic potential for managing these complications. This study aimed to explore the therapeutic effects and potential molecular mechanisms of RM on BBB injury and brain injury in septic rats. Septic rat models were constructed using cecal ligation and puncture (CLP), with 75 rats randomly assigned to five groups (15 rats per group). RM (5 mg/kg, 10 mg/kg, and 20 mg/kg) was injected intraperitoneally to treat the rats. Neurobehavioral and cognitive functions were evaluated via neurological scores, water maze, and Y-maze tests. Brain water content was measured using the dry-wet weight method, and BBB permeability was assessed with Evans blue staining. Oxidative stress and inflammatory markers were detected using enzyme-linked immunosorbent assays and biochemical kits. Western blot analysis was performed to evaluate RM's effects on TLR4/NF-κB pathway proteins. RM treatment alleviated neurobehavioral and cognitive dysfunction while reducing inflammation and oxidative stress in septic rat brain tissue, with 10 mg/kg RM showing the greatest efficacy. RM also reduced brain water content and BBB damage, downregulating TLR4/NF-κB pathway proteins. These findings suggest that RM can effectively alleviate blood-brain barrier and brain injury in septic rats by inhibiting the TLR4/NF-κB pathway. The therapeutic effects observed may pave the way for future clinical research into RM's use for managing sepsis-associated brain injury.