Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou 510080, China; Department of Medical Imaging, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangdong 510060, China.
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
Exp Neurol. 2024 Dec;382:114970. doi: 10.1016/j.expneurol.2024.114970. Epub 2024 Sep 24.
This study aimed to explore the characteristics of post-stroke sleep dysfunction and verify their association with gut dysbiosis and the related amino acid metabolism disorders. This was achieved by using fecal microbiota transplantation (FMT) in a non-human primate stroke model.
Twenty adult male cynomolgus monkeys were divided into the sham (n = 4), middle cerebral artery occlusion (MCAO, n = 5), MCAO + FMT (n = 3), and donor (n = 8) groups. The MCAO+FMT group received FMT at post-MCAO week 4. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine (Gln) in the cerebrospinal fluid (CSF) were measured at baseline and postoperative weeks 4, 8, and 12.
At postoperative weeks 4, 8, and 12, the MCAO group showed decreased sleep efficiency, measured as the percentage of sleep during the whole night (82.3 ± 3.2 % vs 91.3 ± 2.5 %, 79.0 ± 3.75 % vs 90.8 ± 3.2 %, and 69.5 ± 4.8 % vs 90.5 ± 2.7 %; all P < 0.05), lower relative abundance of Lactobacillus (all P < 0.05), and reduced GABA concentrations in the CSF (317.3 ± 30.6 nmol/L vs 437.7 ± 25.6 nmol/L, 303.1 ± 48.9 nmol/L vs 4 40.9 ± 37.8 nmol/L, and 337.9 ± 49.4 nmol/L vs 457.4 ± 39.2 nmol/L; all P < 0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7 ± 1.1 % vs 79.0 ± 3.75 %, and 84.1 ± 2.0 % vs 69.5 ± 4.8 %; both P < 0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1 ± 25.4 nmol/L vs 303.1 ± 48.9 nmol/L, P < 0.05) was higher in the MCAO+FMT group than in the MCAO group.
Post-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as Lactobacillus, GABA, and Gln in the CSF and can be ameliorated using FMT.
本研究旨在探索脑卒中后睡眠功能障碍的特征，并验证其与肠道菌群失调及相关氨基酸代谢紊乱的关系。我们通过非人类灵长类动物脑卒中模型进行粪便微生物群移植（FMT）来实现这一目标。
20 只成年雄性食蟹猴被分为假手术组（n=4）、大脑中动脉闭塞组（MCAO，n=5）、MCAO+FMT 组（n=3）和供体组（n=8）。MCAO+FMT 组在 MCAO 后第 4 周接受 FMT。在基线和术后第 4、8 和 12 周测量睡眠参数、肠道微生物群、脑脊液（CSF）中的γ-氨基丁酸（GABA）和谷氨酰胺（Gln）。
在术后第 4、8 和 12 周，MCAO 组的睡眠效率降低，表现为整个夜间睡眠的百分比（82.3±3.2%比 91.3±2.5%，79.0±3.75%比 90.8±3.2%和 69.5±4.8%比 90.5±2.7%；均 P<0.05），乳杆菌的相对丰度较低（均 P<0.05），CSF 中 GABA 浓度降低（317.3±30.6nmol/L 比 437.7±25.6nmol/L，303.1±48.9nmol/L 比 440.9±37.8nmol/L 和 337.9±49.4nmol/L 比 457.4±39.2nmol/L；均 P<0.05）。与假手术组相比。MCAO+FMT 组在 FMT 后第 4 和 8 周的睡眠效率（84.7±1.1%比 79.0±3.75%和 84.1±2.0%比 69.5±4.8%；均 P<0.05）和 FMT 后第 4 周 CSF 中的 GABA 浓度（403.1±25.4nmol/L 比 303.1±48.9nmol/L，P<0.05）高于 MCAO 组。
猴脑卒中后睡眠功能障碍的特征是睡眠一致性受损，与 CSF 中益生菌（如乳杆菌）、GABA 和 Gln 水平降低有关，可通过 FMT 改善。
