The Immune Response of the Human Brain to Abdominal Surgery
The Immune Response of the Human Brain to Abdominal Surgery
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DOI：
10.1002/ana.24909
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发表时间：
2017-04-01
影响因子：
11.2
通讯作者：
Eriksson, Lars I.
中科院分区：
文献类型：
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作者：
Forsberg, Anton;Cervenka, Simon;Eriksson, Lars I.
目的：手术引发全身炎症反应，到达大脑，与免疫激活和认知能力下降有关。尽管临床前研究已经部分描述了这种系统到大脑的信号通路，但我们缺乏关于这些变化如何在人类中出现的信息。本研究通过正电子发射断层扫描（PET）研究腹部手术对人脑免疫系统的短期和长期影响，包括血液免疫反应性、血浆炎症生物标志物和认知功能。方法：选取全麻下行前列腺切除术的男性8例。术前（基线）、术后3 - 4天和3个月后，使用[C-11]PBR28脑PET成像检查患者，以评估脑免疫细胞激活情况。同时，评估全身炎症生物标志物，体外血液测试对脂多糖（LPS）刺激的免疫反应性和认知功能。结果：患者术后3 ~ 4天灰质[C-11]PBR28结合整体较基线下调26 +/- 26%（平均+/-标准差）（p=0.023）， 3个月后恢复甚至回升。lps诱导的促炎标志物肿瘤坏死因子-a在术后第3 - 4天血液中释放减少（41 +/- 39%），与[C-11]PBR28分布体积的变化相对应。术后3 ~ 4天及3个月Stroop Color-Word Test表现变化与[C-11]PBR28结合变化相关（p=0.027）。解释：这项研究将手术后大脑免疫系统变化的临床前数据转化为人类，并提示人类大脑与外周先天免疫系统的炎症反应之间存在相互作用。这些发现可能与术后认知功能损伤有关。
Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function.Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [C-11]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed.Results: Patients showed a global downregulation of gray matter [C-11]PBR28 binding of 26 +/- 26% (mean +/- standard deviation) at 3 to 4 days postoperatively compared to baseline (p=0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 +/- 39%) on the 3rd to 4th postoperative day, corresponding to changes in [C-11]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [C-11]PBR28 binding (p=0.027).Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function.