Perioperative neurocognitive disorders have been widely recognized as common adverse events after surgical intervention. Aging is one of the most important independent risk factors for worsened cognitive outcome, and this deterioration is linked to exacerbated microglia‐mediated neuroinflammation in the aged brain. Under pathological stimulation, microglia are capable of polarizing toward proinflammatory M1 and anti‐inflammatory M2 phenotypes. In the present study, we examined how aging affects microglial responses and neuroinflammation following peripheral surgery. Adult (2‐3 months) and aged (18 months old) male C57/BL6 mice were subjected to tibial fracture or sham surgery. Aged mice exhibited higher level of tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in the hippocampus. The expression of synaptic protein synaptophysin (SYP) was also markedly reduced in the aged brain after the surgery. Both adult and aged mice showed significant increases in M1 microglial polarization (CD16/32). In contrast, tibial fracture surgery induced a decreased M2 microglial polarization (CD206, Ym1/2, Arg1) in aged brain but enhanced M2 microglial polarization in adult brain. Aged mice have upregulated voltage‐gated proton channel (Hv1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression compared with adult mice. The percentage of CD16/32‐positive M1 microglia colabeling with Hv1 was higher in aged mice after tibial fracture surgery. Thus, Hv1/NADPH oxidase upregulation in the aged brain may shift the dynamic equilibrium of microglial activation toward M1 polarization and exaggerate postoperative neuroinflammatory responses after peripheral surgical intervention.
A novel Cu(TFA)2-catalyzed oxidative tandem cyclization/1,2-alkyl migration of readily available enamino amides for the synthesis of pyrrolin-4-ones has been developed. The reaction tolerates a wide range of functional groups and is a reliable method for the rapid synthesis of substituted pyrrolin-4-ones in high yields under mild conditions.
A novel and efficient copper-catalyzed tandem oxidative cyclization/1,2-amino migration of readily available enamino esters for the synthesis of substituted pyrroles has been developed. In this reaction, one C-N bond was cleaved, and two new C-N bonds and one C(sp)-C(sp) bond were constructed in one pot. This catalytic system has the obvious advantages of mild reaction conditions and the use of oxygen as the oxidant. The reaction tolerates a wide range of functional groups and is a reliable method for the straightforward synthesis of valuable aminomethyl-substituted pyrroles in good yields.
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