Prophylactic lithium alleviates splenectomy-induced cognitive dysfunction possibly by inhibiting hippocampal TLR4 activation in aged rats.

摘要: Though the pathogenesis of postoperative cognitive dysfunction (POCD) remains unclear, evidence is accumulating for a pivotal role neuroinflammation in disease process. Advanced age and severe surgical trauma are two main risk factors POCD. Lithium, neuroprotective agent, can alleviate peripheral surgery-induced memory impairment aged rats. The results vivo vitro experiments also showed that toll like receptor 4 (TLR4) was associated with occurrence development So we hypothesized inhibition TLR4 signaling hippocampus maybe involved protective effects prophylactic lithium on inflammation In present study, incubated BV-2 microglia 1μg/ml lipopolysaccharide (LPS) to mimic vitro. We found pretreatment 10mM or 100nM siRNA could inhibit tumor necrosis factor (TNF)-α mRNA expression induced by LPS microglia. Furthermore, combination even decreased their baseline levels, which may be vital neuroinflammation. further undergone experiment. Then, firstly demonstrated 2mM/kg alleviated splenectomy-induced impairments, splenectomy-associated systemic, central, hippocampal TNF-α interleukin (IL)-1β reduced increase CD11b(+) area CA1 region caused surgery. splenectomy merely increased TLR2 levels At last, confirmed TLR4/NF-κB splenectomy. Taken together, these demonstrate inactivation contribute POCD inhibiting systemic especially