较之大剂量异氟醚麻醉,右美托咪定+小剂量异氟醚增加大鼠大脑神经胶质-淋巴通路途径脑脊液转运

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Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane

  摘 要  
1
背景与目的
3
结果
2
方法
4
结论

背景与目的:神经胶质-淋巴通路途径脑脊液转运贯穿全脑,从而有利于代谢废物的排除。这条通路的独特之处在于其功能取决于大脑的意识状态,并与去甲肾上腺素的活性有关。目前的观点认为所有的麻醉药均能通过使意识消失增加神经胶质-淋巴转运。这意味着只要麻醉药物能引起意识消失,就能影响神经胶质-淋巴的转运,而与麻醉药物的作用机制无关。我们通过比较右旋美托咪定(具有降低去甲肾上腺素的辅助作用)和异氟烷(没有这一作用)来验证这一假说。

1

方法:将雌性大鼠随机分为异氟醚麻醉组和右美托咪定+小剂量异氟醚组(n=8)。连续记录各组大鼠生理指标及脑电图。通过增强磁共振成像对神经胶质-淋巴的转运进行定量。在T1相获得脑脊液、灰质和白质体积,通过磁共振血管造影渡越时间获得血管直径。

结果:右美托咪啶+小剂量异氟烷组神经胶质-淋巴转运较异氟醚麻醉提高了32%。在海马,右美托咪啶+小剂量异氟烷组神经胶质-淋巴液的清除率比远超过异氟烷组的6倍。两种麻醉方案中大鼠的呼吸和血气状况相当。右美托咪啶+小剂量异氟烷组可以观察到纺锤波振荡(9至15赫兹),而异氟醚麻醉的大鼠并未观察到此种现象。

结论:我们推测,麻醉药物对神经胶质-淋巴转运途径影响不止是意识消失还应有其他机制,其中之一便是去甲肾上腺素释放的抑制。

    原始文献来源   

Benveniste H, Lee H, Ding F  Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane  Anesthesiology. Dec,2017;127(6):976-988. doi: 10.1097/ALN.0000000000001888.

Background:The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not.

Methods: Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats.

Results: Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane whencompared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-doseisoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats.

 Conclusions:We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release.

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