Blocking Kv1.3 potassium channels prevents postoperative neuroinflammation and cognitive decline without impairing wound healing in mice
Blocking Kv1.3 potassium channels prevents postoperative neuroinflammation and cognitive decline without impairing wound healing in mice
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DOI：
10.1016/j.bja.2020.05.018
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发表时间：
2020-09-01
影响因子：
9.8
通讯作者：
Maze, Mervyn
中科院分区：
文献类型：
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作者：
Lai, Ieng K.;Valdearcos, Martin;Maze, Mervyn
背景：术后认知功能下降(PCD)需要小胶质细胞的激活。电压门控Kv1.3钾通道参与小胶质细胞的激活。我们确定了Kv1.3在PCD中的作用，以及苯氧基烷氧基补骨脂素-1(PAP-1)抑制Kv1.3在预防PCD中的有效性和安全性。方法：经过机构批准，我们评估了Kv1.3缺陷小鼠(Kv1.3(-/-))是否表现出PCD，表现为胫骨骨折手术导致厌恶冰冻行为的下降，以及PAP-1是否可以预防PCD和易受PCD饮食诱导的肥胖(DIO)小鼠的术后神经炎症。我们还评估了PAP-1是否改变了术后外周炎症或胫骨骨折愈合。结果：术后Kv1.3(-/-)小鼠的冷冻行为没有改变。在DIO小鼠中，PAP-1阻止了术后(I)冰冻行为的减弱(54[17.3]%vs 33.4[12.7]%；P=0.03)，(Ii)根据大小激活海马区小胶质细胞(130[31]像素vs 249[49]；P
Background: Postoperative cognitive decline (PCD) requires microglial activation. Voltage-gated Kv1.3 potassium channels are involved in microglial activation. We determined the role of Kv1.3 in PCD and the efficacy and safety of inhibiting Kv1.3 with phenoxyalkoxypsoralen-1 (PAP-1) in preventing PCD in a mouse model.Methods: After institutional approval, we assessed whether Kv1.3-deficient mice (Kv1.3(-/-)) exhibited PCD, evidenced by tibial-fracture surgery-induced decline in aversive freezing behaviour, and whether PAP-1 could prevent PCD and postoperative neuroinflammation in PCD-vulnerable diet-induced obese (DIO) mice. We also evaluated whether PAP-1 altered either postoperative peripheral inflammation or tibial-fracture healing.Results: Freezing behaviour was unaltered in postoperative Kv1.3(-/-) mice. In DIO mice, PAP-1 prevented postoperative (i) attenuation of freezing behaviour (54 [17.3]% vs 33.4 [12.7]%; P=0.03), (ii) hippocampal microglial activation by size (130 [31] pixels vs 249 [49]; P