Dexmedetomidine alleviates cognitive impairment by reducing blood-brain barrier interruption and neuroinflammation via regulating Th1/Th2/Th17 polarization in an experimental sepsis model of mice.

Clinical studies have shown that dexmedetomidine (DEX) reduces mortality and inflammation in patients with sepsis, and ameliorates cognitive decline in both postoperative and critical care patients. This study aims to explain the neuroprotective effects provided by DEX in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Mice were treated with DEX intraperitoneally three times every two hours after CLP. The survival rate, body weight, and clinical scores were recorded each day. Morris water maze (MWM) and fear conditioning tests were used to evaluate cognitive function. Blood brain barrier (BBB) permeability, hippocampal inflammation, hippocampal neural apoptosis, and T helper (Th) cell subgroups were assessed. Furthermore, Atipamezole was used to verify that the potential neuroprotective effects in the sepsis-associated encephalopathy (SAE) were mediated by DEX. Compared with the Sham group, CLP mice showed significant cognitive impairment, BBB interruption, excessive neuroinflammation, and neuronal apoptosis. These detrimental effects of CLP were attenuated by DEX. Furthermore, we found that DEX corrects peripheral Th1/Th2/Th17 shift and reduces proinflammatory cytokines in the hippocampus. Additionally, atipamezole prevented DEX's protective effect. Taken together, DEX alleviates cognitive impairments by reducing blood-brain barrier interruption and neuroinflammation by regulating Th1/Th2/Th17 polarization.