2012年9月17日 讯 /生物谷BIOON/ --一种称为“术后认知能力下降”的综合征（post-operative cognitive decline）在成年人中常表现为认知能力的缺失，尤其是其经过手术后所表现出的认知力下降的症状。实际上，一些具有阿尔兹海默症发病症状的病人经过手术后也会出现认知能力的下降的症状。一年以前，来自宾夕法尼亚大学的研究者报道了通过脑脊髓液反应的阿尔兹海默氏症患者的病理学表现或许在其术后和麻醉后表现的更加严重。然而到底是麻醉药物还是手术操作本身所引发的病理严重目前并不清楚，这项研究中，研究者揭示了手术，而不是麻醉对患者痴呆脆弱的大脑具有较为深远的影响。相关研究刊登在了国际杂志Annals of Surgery上。
这项研究中，研究者使携带有人类阿尔兹海默症疾病（AD）基因的小鼠单独暴露于麻醉中或者同时进行麻醉和手术操作。手术类似于阑尾炎切除或者结肠切除等，类似于人类非常普通的手术。通过研究发现手术可以增加小鼠阿尔兹海默症疾病的发病，而且相比只接受麻醉来讲，同时接受手术的小鼠也表现出了明显的认知能力下降，时间至少持续14周。
研究者通过进一步深入研究法案现，连接外科手术和认知能力效应的机制看起来是由于炎症所致，以为炎症过程是手术中并发存在的，然而炎症过程如何影响大脑发挥作用，以及为何会加速AD的病症表现，研究者依然不清楚。
术后三个月后，大部分人的认知能力都可以恢复，这项研究揭示了，在敏感性大脑中，术后认识的暂时缺失或许是不可逆的。然而研究中也揭示了，炎症表现或许是隐藏在最深处的一个机制，研究者首先需要证实这些研究发现，并且开始展开抗炎疗法来尽可能减少对患者的损伤。相关研究由美国国家老年化研究所提供资助。（生物谷Bioon.com）
编译自：Surgery Has a More Profound Effect Than Anesthesia On Brain Pathology and Cognition in Alzheimer's Animal Model
doi:10.1097/SLA.0b013e318269d623
PMC:
PMID:
Modulation of Murine Alzheimer Pathogenesis and Behavior by Surgery
Tang, Junxia X. PhD; Mardini, Feras BS; Janik, Luke S. MD; Garrity, Sean T. BS; Li, Rosie Q. BS; Bachlani, Gulnaz BS; Eckenhoff, Roderic G. MD; Eckenhoff, Maryellen F. PhD
Objective: Previous research suggests that a link between anesthetic exposure and Alzheimer disease exists. Because anesthetics are rarely given alone, we ask whether addition of surgery further modulates Alzheimer disease. Background: Cognitive dysfunction occurs after surgery in humans. Anesthesia alone produces cognitive decline in both older wild-type (WT) mice and rats, and the addition of surgery produces transient decline in young, adult WT mice. Because neuroinflammation has been implicated and occurs early in Alzheimer disease, we hypothesized that the neuroinflammatory stress associated with surgery would accelerate the progression of Alzheimer disease. Methods: Cecal ligation and excision were performed on presymptomatic 5- to 11-month-old triple-transgenic Alzheimer disease (3xTgAD) and C57BL/6 WT mice under desflurane anesthesia. Surgery animals were compared with aged-matched 3xTgAD and WT mice exposed to air or desflurane alone. Cognitive function was assessed via Morris water maze at 2 and 13 weeks postoperatively. Amyloid and tau pathology and inflammation and synaptic markers were quantified with immunohistochemistry, Luminex assay, enzyme-linked immunosorbent assay, or Western blot assays. Results: A significant cognitive impairment in 3xTgAD mice that underwent surgery compared with air or desflurane controls persisted to at least 14 weeks after surgery. Microglial activation, amyloidopathy, and tauopathy were enhanced by surgery as compared with desflurane alone. No differences between surgery, anesthetic, or air controls were detected in WT mice Conclusions: Surgery causes a durable increment in Alzheimer pathogenesis, primarily through a transient activation of neuroinflammation. (C) 2012 Lippincott Williams & Wilkins, Inc.
