Abstract
Dexmedetomidine (DEX) is known to provide neuroprotective effect in the central nervous system. However, the detailed mechanism remains far more elusive. This study was designed to investigate the relevant mechanisms of DEX's neuroprotective effect. Sprague–Dawley (SD) rats were injected with dexmedetomidine and/or Lipopolysaccharide (LPS) intraperitoneally, and inflammatory cytokines in serum and in the hippocampus were measured by enzyme linked immunosorbent assay (ELISA). NF-κB in the brain tissue extracts was analyzed with western-blot. Then, we investigated whether NF-κB inhibitor prevents the elevation of inflammatory cytokines in rats injected with LPS. Our results indicated that compared with the control group, the rats exposed to LPS showed significant cognitive dysfunction. When compared to controls, the levels of TNF-α and IL-6 in the serum and hippocampus homogenate were increased in rats treated with LPS. DEX pretreatment inhibited the rats' TNF-α, IL-6 and NF-κB levels induced by LPS. In response to LPS, PDTC pretreatment restrains the production of proinflammatory cytokines (TNF-α and IL-6). Rats treated with PDTC and DEX alongside LPS exhibited less TNF-α and IL-6 than the LPS treated group. In combination, PDTC and DEX showed addictive effects. Our data suggest that DEX exerts a neuroprotective effect through NF-κB in part after LPS-induced cognitive dysfunction.
Highlights
Neuroinflammation plays a pivotal role in the pathophysiology of neurocognitive disorders such as Alzheimer’s disease and postoperative cognitive dysfunction(POCD) [1]
To estimate the effect of DEX on inflammatory factors, the levels of TNF-α and IL-6 in the serum and hippocampus homogenate were detected by enzyme linked immunosorbent assay (ELISA)
Our results indicated that DEX at concentration of 50 μg/kg significantly inhibited rats’ TNF-α and IL-6 level induced by LPS, while 5 μg/kg show no anti-inflammatory effect in rats (Fig 2) (Table C, D, E and F in S1 File)
Summary
Neuroinflammation plays a pivotal role in the pathophysiology of neurocognitive disorders such as Alzheimer’s disease and postoperative cognitive dysfunction(POCD) [1]. Lipopolysaccharide (LPS) is one of the most potent activators for stimulating pro-inflammatory cytokines release in experimental animals and humans [2]. Studies have shown that systemic LPS causes memory impairment [3], chronic neuroinflammation, and progressive neurodegeneration [4]. Dexmedetomidine inhibits hippocampus inflammatory reaction by NF-κB pathway
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