Postoperative cognitive dysfunction (POCD) is commonly observed in perioperative care following major surgery and general anesthesia in elderly individuals. No preventive or interventional agents have been established so far. Although the role of interleukin-1β (IL-1β)-mediated neuroinflammation following surgery and anesthesia is strongly implicated in POCD, the exact mechanism of action remains to be explored. Growing evidence has shown that mitochondria-derived reactive oxygen species (mtROS) are closely linked to IL-1β expression through a redox sensor known as the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Therefore, we hypothesize that the mechanisms underlying POCD involve the mtROS/NLRP3 inflammasome/IL-1β signaling pathway. Furthermore, we speculate that cholinergic anti-inflammatory pathway induced by α7 nicotinic acetylcholine receptor (a7nAChR) may be the potential upstream of mtROS/NLRP3 inflammasome/IL-1β signaling pathway in POCD. For validating the hypotheses, we provide experimental plan involving different paradigms namely; microglial cells and behavioral studies. The link between mtROS, the NLRP3 inflammasome, and IL-1β within and between these different stages in combination with mtROS and NLRP3 inflammasome agonists and inhibitors could be explored using techniques, such as knockout mice, small interference ribonucleic acid, flow cytometry, co-immunoprecipitation, and the Morris Water Maze test. We conclude that the NLRP3 inflammasome is a new preventive and therapeutic target for POCD.
Nicotine has long been considered a potent therapeutic agent for neuroprotection. This study reported the positive effect of nicotine treatment on cognitive dysfunction after partial hepatectomy in aged rats. Furthermore, the underlying mechanism may involve activation of the BDNF/TrkB signaling pathway and inhibition of the NF-κB signaling pathway in the hippocampus.
BackgroundThis study aimed to evaluate the effects of lidocaine treatment on cognitive impairment in aged patients undergoing spine surgery and to explore the underlying mechanism.Material/MethodsPatients were randomly divided into 2 treatment groups: (1) saline (control) and (2) lidocaine. After induction of anesthesia, the lidocaine group received lidocaine as a bolus of 1 mg/kg over 5 minutes, followed by a continuous infusion at 1.5 mg/kg/h until the end of the surgery. We examined the effects of lidocaine treatment on the improvement of cognitive function using the Mini-Mental State Examination (MMSE) at preoperation and 3 days postoperation. Serum samples were collected to assess the levels of IL-6, TNF-α, MDA, S100β, and NSE before inducing anesthesia, at the end of surgery, and 3 days after the end of surgery.ResultsWe found that the MMSE scores in the lidocaine group were markedly higher than those in the control group at 3 days after surgery. Moreover, lidocaine treatment markedly suppressed the release of IL-6, S100β, and NSE into the serum at the end of surgery and 3 days after the end of surgery. In the control group, serum MDA levels increased by 3 days after the end of surgery. The lidocaine group had lower serum MDA levels than those in the control group.ConclusionsLidocaine may be an effective neuroprotective agent in treating early postoperative cognitive dysfunction in elderly patients undergoing spine surgery.
Efficient yet low-cost electrocatalysts for the oxygen reduction reaction (ORR) are highly desirable for energy systems such as metal-air batteries and fuel cells. Herein, we report the synthesis of efficient cobalt-modified nitrogen-doped carbon (NÀ C/Co) electrocatalysts by using a one-pot pyrolysis. The abundant source of N in g-C 3 N 4 contributes to the in situ N doping in the carbon matrix, which favors the formation of Co-related catalytic active sites. The NÀ C/Co-1 (prepared with 1 mmol Co salt) sample exhibits the best performance towards the ORR, with a positive half-wave potential of 0.86 V (vs. the reversible hydrogen electrode, RHE), high stability and excellent methanol tolerance, which outperforms the commercial Pt/C catalyst. We find that the high performance is dependent on the optimal content of Co that can achieve the maximum amount of CoÀ N x catalytic species. In addition, we reveal that the size effect of Co nanoparticles is not the determining factor for the ORR activity in the current system, as the kinetics of the ORR reaction is dominantly determined by the active sites derived from CoÀ N x species. By exploiting the NÀ C/Co-1 sample as an air cathode catalyst, the assembled Zn-air battery presents a maximal power density of 153 mW cm À 2 as well as good durability during continuous cycle tests.
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