Kawano Takashi, Eguchi Satoru, Iwata Hideki, Tamura Takahiko, Kumagai Naoko, Yokoyama Masataka
From the Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Kochi, Japan (T.K., H.I., T.T., M.Y.); Department of Dental Anesthesiology, Tokushima University School of Dentistry, Tokushima, Japan (S.E.); and Department of Advanced Medical Technologies, Clinical Trial Center, Kochi Medical School, Kochi, Japan (N.K.).
Anesthesiology. 2015 Jul;123(1):160-70. doi: 10.1097/ALN.0000000000000697.
Sustained neuroinflammation may contribute to the pathogenesis of postoperative cognitive dysfunction (POCD). Here, the authors evaluated the preventive effect of preoperative environmental enrichment (PEE) on the development of neuroinflammation and concomitant POCD in a rat abdominal surgery model.
Young and aged rats were assigned to one of four groups using a 2 × 2 experimental design: PEE versus sedentary condition for 14 days, by abdominal surgery versus anesthesia alone (n = 8 in each group). After a 7-day postsurgical recovery period, cognitive function was assessed using a novel object recognition test, followed by measurement of hippocampal levels of proinflammatory cytokines. Under identical conditions, microglia were isolated from the hippocampus for assessment of cytokine response to lipopolysaccharide.
In the sedentary group, aged, but not young, rats receiving surgery showed memory deficits (novel object preference during testing phase of 54.6 ± 7.8% vs. 76.9 ± 11.3% in nonsurgery group, P < 0.05) and increased hippocampal levels of cytokines compared with nonsurgical rats. PEE had no effects on novel object preference in nonsurgery animals (78.6 ± 10.7%), whereas it attenuated surgery-induced impairment of novel object preference (70.9 ± 15.0%, P < 0.05 vs. sedentary/surgery group) as well as increase of cytokine levels in hippocampus. Furthermore, upon ex vivo stimulation with lipopolysaccharide, cytokines release from hippocampal microglia isolated from aged rats before intervention was significantly higher in comparison with young rats. PEE resulted in reduction of these age-related microglial phenotypic changes.
PEE could prevent the development of neuroinflammation and related POCD in aged rats by reversion of a proinflammatory phenotype of hippocampal microglia.
持续性神经炎症可能参与术后认知功能障碍（POCD）的发病机制。在此，作者在大鼠腹部手术模型中评估了术前环境富集（PEE）对神经炎症发展及伴随的POCD的预防作用。
采用2×2实验设计将年轻和老年大鼠分为四组：14天的PEE组与久坐组，接受腹部手术组与仅接受麻醉组（每组n = 8）。术后7天恢复期后，使用新颖物体识别测试评估认知功能，随后测量海马中促炎细胞因子水平。在相同条件下，从海马中分离小胶质细胞以评估其对脂多糖的细胞因子反应。
在久坐组中，接受手术的老年大鼠而非年轻大鼠出现记忆缺陷（测试阶段新颖物体偏好率为54.6±7.8%，而非手术组为76.9±11.3%，P < 0.05），且与非手术大鼠相比，海马中细胞因子水平升高。PEE对非手术动物的新颖物体偏好无影响（78.6±10.7%），而它减轻了手术诱导的新颖物体偏好损害（70.9±15.0%，与久坐/手术组相比P < 0.05）以及海马中细胞因子水平的升高。此外，在用脂多糖进行体外刺激时，与年轻大鼠相比，干预前从老年大鼠分离的海马小胶质细胞释放的细胞因子明显更高。PEE导致这些与年龄相关的小胶质细胞表型变化减少。
PEE可通过逆转海马小胶质细胞的促炎表型来预防老年大鼠神经炎症及相关POCD的发展。
