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摘要: 类淋巴系统(GS)是依赖于水通道蛋白4(AQP4)的液体运输系统，在星形胶质细胞末端极化，分布于全脑，促进脑脊液(CSF)-组织液(ISF)物质交换，具有清除脑内代谢物功能，起到维持CSF-ISF平衡的作用。越来越多的证据显示，GS与脑功能障碍病理改变及转归密切相关。近年来的研究表明，GS功能障碍在脑水肿、血脑屏障(BBB)破坏、免疫细胞浸润、神经炎症、神经元凋亡等病理生理过程中发挥着关键作用，与颅脑外伤(TBI)、脑积水、癫痫、偏头痛、阿尔茨海默病(AD)等多种神经功能障碍有关。脓毒症相关脑病(SAE)由内皮/胶质细胞激活、血脑屏障通透性增加、缺氧、神经递质失衡、胶质细胞激活、轴突和神经元缺失引起的炎症，以局灶性神经症状为特征，临床症状主要以谵妄为主。目前研究发现GS对SAE后脑脊液循环及脑水肿的发生有一定影响。本文就GS与SAE相关性进行综述，通过GS的结构、功能及相关影响因素的变化对SAE的作用，以及在基础研究中有待解决的问题进行综述，旨在为SAE的防治提供参考。Abstract: The lymphoid system is a liquid transport system dependent on aquaporin 4, which is polarized at the end of astrocytes, distributed in the whole brain, promotes the exchange of cerebrospinal fluid(CSF) and tissue fluid. It can function to remove metabolites in the brain, and maintain the balance of CSF and tissue fluid. Increasing evidence shows that the lymphoid system is closely related to the pathological changes and outcome of brain dysfunction. Recent studies have shown that lymphoid system dysfunction is associated with various neurological disorders, including craniocerebral trauma, hydrocephalus, epilepsy, migraine, and Alzheimer's disease. It also plays a key role in the pathophysiological processes such as brain edema, blood-brain barrier destruction, immune cell infiltration, neuroinflammation, and neuronal apoptosis. Sepsis-related encephalopathy is caused by endothelial and glial cell activation, increased BBB permeability, hypoxia, neurotransmitter imbalance, glial cell activation, axonal and neuronal loss, and is characterized by focal neurosis. Its major clinical symptom is delirium. The present study has found that the lymphoid system has some influence on the CSF circulation and cerebral oedema after sepsis-related encephalopathy. This paper reviews the correlation of the lymphatic-like system and sepsis-related encephalopathy, aiming to provide a reference for the prevention and treatment of sepsis-related encephalopathy by summurizing the effect of the changes of GS structure, fuction and related influencing factors on SAE, and the remaining problems in basic research.
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[1] Zhao L, Gao Y, Guo S, et al. Sepsis-Associated Encephalopathy: Insight into Injury and Pathogenesis[J]. CNS Neurol Disord Drug Targets, 2021, 20(2): 112-124.
[2] Manabe T, Heneka MT. Cerebral dysfunctions caused by sepsis during ageing[J]. Nat Rev Immunol, 2022, 22(7): 444-458. doi: 10.1038/s41577-021-00643-7
[3] Benveniste H, Liu X, Koundal S, et al. The Glymphatic System and Waste Clearance with Brain Aging: A Review[J]. Gerontology, 2019, 65(2): 106-119. doi: 10.1159/000490349
[4] Ren X, Liu S, Lian C, et al. Dysfunction of the Glymphatic System as a Potential Mechanism of Perioperative Neurocognitive Disorders[J]. Front Aging Neurosci, 2021, 13: 659457. doi: 10.3389/fnagi.2021.659457
[5] Rasmussen MK, Mestre H, Nedergaard M. Fluid transport in the brain[J]. Physiol Rev, 2022, 102(2): 1025-1151. doi: 10.1152/physrev.00031.2020
[6] 施翔鹏, 方芳, 仓静. 类淋巴系统功能及其影响因素[J]. 临床麻醉学杂志, 2019, 35(4): 401-404. https://www.cnki.com.cn/Article/CJFDTOTAL-LCMZ201904029.htm
[7] Chung HY, Wickel J, Brunkhorst FM, et al. Sepsis-Associated Encephalopathy: From Delirium to Dementia[J]? J Clin Med, 2020, 9(3): 703. doi: 10.3390/jcm9030703
[8] Crippa IA, Subirà C, Vincent JL, et al. Impaired cerebral autoregulation is associated with brain dysfunction in patients with sepsis[J]. Crit Care, 2018, 22(1): 327. doi: 10.1186/s13054-018-2258-8
[9] Mestre H, Du T, Sweeney AM, et al. Cerebrospinal fluid influx drives acute ischemic tissue swelling[J]. Science, 2020, 367(6483): eaax7171. doi: 10.1126/science.aax7171
[10] Salman MM, Kitchen P, Halsey A, et al. Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis[J]. Brain, 2022, 145(1): 64-75. doi: 10.1093/brain/awab311
[11] Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders[J]. Lancet Neurol, 2018, 17(11): 1016-1024. doi: 10.1016/S1474-4422(18)30318-1
[12] Del Puerto A, Pose-Utrilla J, Simón-García A, et al. Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation[J]. Mol Psychiatry, 2021, 26(11): 6411-6426. doi: 10.1038/s41380-021-01127-9
[13] Hasan-Olive MM, Enger R, Hansson HA, et al. Loss of perivascular aquaporin-4 in idiopathic normal pressure hydrocephalus[J]. Glia, 2019, 67(1): 91-100. doi: 10.1002/glia.23528
[14] Trillo-Contreras JL, Toledo-Aral JJ, Villadiego J, et al. Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus[J]. Int J Mol Sci, 2021, 22(18): 9745. doi: 10.3390/ijms22189745
[15] Nwafor DC, Brichacek AL, Mohammad AS, et al. Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment[J]. J Cent Nerv Syst Dis, 2019, 11: 1179573519840652.
[16] Lv T, Zhao B, Hu Q, et al. The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment[J]. Front Aging Neurosci, 2021, 13: 689098. doi: 10.3389/fnagi.2021.689098
[17] Braun M, Iliff JJ. The impact of neurovascular, blood-brain barrier, and glymphatic dysfunction in neurodegenerative and metabolic diseases[J]. Int Rev Neurobiol, 2020, 154: 413-436.
[18] Ueno M, Chiba Y, Murakami R, et al. Disturbance of Intracerebral Fluid Clearance and Blood-Brain Barrier in Vascular Cognitive Impairment[J]. Int J Mol Sci, 2019, 20(10): 2600. doi: 10.3390/ijms20102600
[19] Yu Y, Wang C, Zhang X, et al. Perfluorooctane sulfonate disrupts the blood brain barrier through the crosstalk between endothelial cells and astrocytes in mice[J]. Environ Pollut, 2020, 256: 113429. doi: 10.1016/j.envpol.2019.113429
[20] 欧茹, 唐亚梅, 李飞, 等. 扩大的血管周围间隙与急性缺血性脑卒中患者神经功能恢复及生活质量的相关性研究[J]. 卒中与神经疾病, 2018, 25(3): 256-259. doi: 10.3969/j.issn.1007-0478.2018.03.004
[21] Wu TT, Su FJ, Feng YQ, et al. Mesenchymal stem cells alleviate AQP-4-dependent glymphatic dysfunction and improve brain distribution of antisense oligonucleotides in BACHD mice[J]. Stem Cells, 2020, 38(2): 218-230. doi: 10.1002/stem.3103
[22] Harrison IF, Ismail O, Machhada A, et al. Impaired glymphatic function and clearance of tau in an Alzheimer's disease model[J]. Brain, 2020, 143(8): 2576-2593. doi: 10.1093/brain/awaa179
[23] Lilius TO, Blomqvist K, Hauglund NL, et al. Dexmedetomidine enhances glymphatic brain delivery of intrathecally administered drugs[J]. J Control Release, 2019, 304: 29-38. doi: 10.1016/j.jconrel.2019.05.005
[24] Ji C, Yu X, Xu W, et al. The role of glymphatic system in the cerebral edema formation after ischemic stroke[J]. Exp Neurol, 2021, 340: 113685. doi: 10.1016/j.expneurol.2021.113685
[25] 易婷, 金硕果, 尹海燕, 等. 脑胶质淋巴系统——脑卒中病理机制的新探索[J]. 中国全科医学, 2022, 25(9): 1136-1140, 1154. doi: 10.12114/j.issn.1007-9572.2021.02.107
[26] Yu P, Venkat P, Chopp M, et al. Deficiency of tPA Exacerbates White Matter Damage, Neuroinflammation, Glymphatic Dysfunction and Cognitive Dysfunction in Aging Mice[J]. Aging Dis, 2019, 10(4): 770-783. doi: 10.14336/AD.2018.0816
[27] Cui H, Wang W, Zheng X, et al. Decreased AQP4 Expression Aggravates ɑ-Synuclein Pathology in Parkinson's Disease Mice, Possibly via Impaired Glymphatic Clearance[J]. J Mol Neurosci, 2021, 71(12): 2500-2513. doi: 10.1007/s12031-021-01836-4
[28] Xu XE, Liu L, Wang YC, et al. Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis[J]. Brain Behav Immun, 2019, 80: 859-870. doi: 10.1016/j.bbi.2019.05.038
[29] Howe MD, Atadja LA, Furr JW, et al. Fibronectin induces the perivascular deposition of cerebrospinal fluid-derived amyloid-β in aging and after stroke[J]. Neurobiol Aging, 2018, 72: 1-13. doi: 10.1016/j.neurobiolaging.2018.07.019
[30] Goulay R, Mena Romo L, Hol EM, et al. From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation[J]. Transl Stroke Res, 2020, 11(4): 601-614. doi: 10.1007/s12975-019-00755-2
[31] He XF, Li G, Li LL, et al. Overexpression of Slit2 decreases neuronal excitotoxicity, accelerates glymphatic clearance, and improves cognition in a multiple microinfarcts model[J]. Mol Brain, 2020, 13(1): 135. doi: 10.1186/s13041-020-00659-5
[32] Golanov EV, Bovshik EI, Wong KK, et al. Subarachnoid hemorrhage-Induced block of cerebrospinal fluid flow: Role of brain coagulation factor Ⅲ(tissue factor)[J]. J Cereb Blood Flow Metab, 2018, 38(5): 793-808. doi: 10.1177/0271678X17701157
[33] Carlstrom LP, Eltanahy A, Perry A, et al. A clinical primer for the glymphatic system[J]. Brain, 2022, 145(3): 843-857. doi: 10.1093/brain/awab428
[34] Zhao P, Le Z, Liu L, et al. Therapeutic Delivery to the Brain via the Lymphatic Vasculature[J]. Nano Lett, 2020, 20(7): 5415-5420. doi: 10.1021/acs.nanolett.0c01806
[35] Plog BA, Mestre H, Olveda GE, et al. Transcranial optical imaging reveals a pathway for optimizing the delivery of immunotherapeutics to the brain[J]. JCI Insight, 2018, 3(23): e126138. doi: 10.1172/jci.insight.126138
[36] Rosu GC, Catalin B, Balseanu TA, et al. Inhibition of Aquaporin 4 Decreases Amyloid Aβ40 Drainage Around Cerebral Vessels[J]. Mol Neurobiol, 2020, 57(11): 4720-4734. doi: 10.1007/s12035-020-02044-8
[37] Xue X, Zhang W, Zhu J, et al. Aquaporin-4 deficiency reduces TGF-β1 in mouse midbrains and exacerbates pathology in experimental Parkinson's disease[J]. J Cell Mol Med, 2019, 23(4): 2568-2582. doi: 10.1111/jcmm.14147
[38] Dadgostar E, Rahimi S, Nikmanzar S, et al. Aquaporin 4 in Traumatic Brain Injury: From Molecular Pathways to Therapeutic Target[J]. Neurochem Res, 2022, 47(4): 860-871. doi: 10.1007/s11064-021-03512-w
[39] Zhou Z, Zhan J, Cai Q, et al. The Water Transport System in Astrocytes-Aquaporins[J]. Cells, 2022, 11(16): 2564. doi: 10.3390/cells11162564
[40] Walch E, Fiacco TA. Honey, I shrunk the extracellular space: Measurements and mechanisms of astrocyte swelling[J]. Glia, 2022, 70(11): 2013-2031. doi: 10.1002/glia.24224
[41] Tice C, McDevitt J, Langford D. Astrocytes, HIV and the Glymphatic System: A Disease of Disrupted Waste Management[J]? Front Cell Infect Microbiol, 2020, 10: 523379. doi: 10.3389/fcimb.2020.523379
[42] 朱丹丹, 于健, 陆莹莹. 脓毒症相关性脑病的发病机制和潜在脑损伤标志物[J]. 实用休克杂志(中英文), 2019, 3(3): 171-175. https://www.cnki.com.cn/Article/CJFDTOTAL-SYYW201903011.htm
[43] 吴秀霞, 张震. 右美托咪定对脓毒症相关性脑病大鼠脑组织神经细胞凋亡的影响[J]. 中华实验外科杂志, 2021, 38(11): 2175-2178. doi: 10.3760/cma.j.cn421213-20210306-01076
[44] 刘威鹏, 高成金, 潘曙明. 前颗粒蛋白在脓毒症中研究进展[J]. 临床急诊杂志, 2020, 21(7): 595-598. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLC202007018.htm
[45] 郭伟, 李平, 陈翠, 等. 脓毒症诱导T细胞功能紊乱及免疫治疗进展[J]. 临床急诊杂志, 2020, 21(9): 758-762. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLC202009017.htm
[46] 郭娜, 宁海慧, 邢博民, 等. Rho/ROCK信号通路在脓毒症相关脏器损伤中的作用及机制研究进展[J]. 临床急诊杂志, 2021, 22(7): 503-507. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLC202107015.htm
[47] Cho EB, Cho HJ, Seok JM, et al. The IL-10-producing regulatory B cells(B10 cells)and regulatory T cell subsets in neuromyelitis optica spectrum disorder[J]. Neurol Sci, 2018, 39(3): 543-549. doi: 10.1007/s10072-018-3248-y
[48] Gao YL, Liu YC, Zhang X, et al. Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy[J]. Front Neurol, 2022, 13: 830784. doi: 10.3389/fneur.2022.830784
[49] Qiu D, Chu X, Hua L, et al. Gpr174-deficient regulatory T cells decrease cytokine storm in septic mice[J]. Cell Death Dis, 2019, 10(3): 233. doi: 10.1038/s41419-019-1462-z
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