Gut microbiome improves postoperative cognitive function by decreasing permeability of the blood-brain barrier in aged mice.,Brain Research Bulletin

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Gut microbiome improves postoperative cognitive function by decreasing permeability of the blood-brain barrier in aged mice.
Brain Research Bulletin ( IF 3.8 ) Pub Date : 2020-09-05 , DOI: 10.1016/j.brainresbull.2020.08.017
Jian Wen ₁ , Yan Ding ₂ , Le Wang ₃ , Ying Xiao ₁

Affiliation

Background

Increased permeability of blood-brain barrier (BBB) is a major pathophysiological mechanism of postoperative cognitive dysfunction (POCD) in the elderly. The reduced beneficial gut microbiome due to aging results in a decline in the production of sodium butyrate (NaB), which might enhance the BBB permeability. The present study investigated whether gut microbiome or NaB could improve the postoperative cognitive function in aged and gut dysbiosis mouse model.

Methods

A total of 210 male C57BL/6 J mice were randomly and equally divided into 7 groups (young control, young anesthesia/surgery, young anesthesia/surgery + antibiotic, aged control, aged anesthesia/surgery, aged anesthesia/surgery + Lactobacillus, aged anesthesia/surgery + NaB). Lactobacillus mix and antibiotic mix were administered by oral gavage to establish the gut dysbiosis and microbiome restoration model. Splenectomy was performed under sevoflurane anesthesia. Spatial memory learning ability was measured by Y maze. BBB permeability was detected by FITC-dextran imaging and brain tissue dextran spectrum. Tight junction (TJ) protein of hippocampus brain tissue was quantitated by Western blot.

Result

Aging and antibiotic mix decreased the expression of the TJ, increased the BBB permeability and induced POCD, which could be reversed by the application of Lactobacillus and NaB.

Conclusion

Lactobacillus and NaB increased the expression of TJ protein between endothelial cells (ECs), reduced the BBB permeability, and consequently protected the postoperative cognitive functions of the aged and gut dysbiosis mice.

中文翻译：

肠道微生物组通过降低老年小鼠血脑屏障的通透性来改善术后认知功能。

背景

血脑屏障（BBB）通透性增加是老年人术后认知功能障碍（POCD）的主要病理生理机制。由于衰老而减少的有益肠道微生物群导致丁酸钠 (NaB) 的产生减少，这可能会增强 BBB 通透性。本研究调查了肠道微生物组或 NaB 是否可以改善老年和肠道生态失调小鼠模型的术后认知功能。

方法

将 210 只雄性 C57BL/6 J 小鼠随机等分为 7 组（年轻对照、年轻麻醉/手术、年轻麻醉/手术+抗生素、老年对照、老年麻醉/手术、老年麻醉/手术+乳酸杆菌、老年麻醉/手术 + NaB）。通过口服管饲法给予乳酸菌混合物和抗生素混合物，以建立肠道菌群失调和微生物组恢复模型。在七氟醚麻醉下进行脾切除术。Y迷宫测量空间记忆学习能力。通过 FITC-葡聚糖成像和脑组织葡聚糖光谱检测 BBB 通透性。通过蛋白质印迹定量海马脑组织的紧密连接（TJ）蛋白。