Glimfatik sistemin ve nörodejeneratif hastalıkların klinik yansımaları

Abstract

Amaç: Beyin, merkezi sinir sisteminin ana unsurlarından biri olup kafatası kemiklerinin oluşturduğu kemik yapısı içerisinde korunmaktadır. Ayrıca özel bir zar sistemi ve seçici geçirgen bir kan bariyeri de bulunmaktadır. Peki her madde beyne rastgele giremiyorsa atık maddeler beyinden nasıl uzaklaştırılıyor? 2012 yılına kadar beyinde lenf sistemi olmadığı düşünülüyordu. İnsan vücudu bir makine gibi düzenli bir sistemle çalışır ve buna vücudun homeostazisi denir. Sinir sistemi ve endokrin sistemi bu dengeyi sağlamada temel bir rol oynar. Sinir sisteminin ana unsurlarından biri olan beyin; bu kadar temel ve önemli görevleri varken, bu biyokimyasal olaylar sonucu oluşan atıklar nasıl uzaklaştırılıyor? Bu literatür incelemesiyle amacımız bu sorulara daha kolay cevap bulmanızı sağlamaktır. Materyal ve Metot: Bu derleme araştırması için mevcut literatür glimfatik sistem açısından sistematik olarak tarandı. Bulgular: Glimfatik sistem beynin atık temizleme mekanizmasıdır. Glimfatik sistemde birçok anatomik yapı yer alır. Astrositler ve aquaporin-4 kanalları bunların en dikkat çekenleriydi. Sonuç: Glimfatik sistem beyinde atık temizleme mekanizması olup birçok önemli fonksiyon mekanizmasına sahiptir. Her ne kadar son yıllarda insan ve hayvan deneyleri ile güncel araştırmalara konu olsa da hala gizemini koruyan bir alandır. Bu sistemin bozulması nörodejeneratif hastalıklarla yakın ilişkilidir. Beyin sağlığı açısından hayati rol oynayan bu sistemin, işleyiş mekanizmasını netleştirmek için daha fazla bilimsel araştırmaya konu olması gerektiği düşüncesindeyiz.

Keywords

• Beyin
• Lenfatik sistem
• Nörodejeneratif hastalıklar
• Nöroanatomi

Clinical reflections of the glymphatic system and neurodegenerative diseases

Abstract

Objective: The brain is one of the main elements of the central nervous system and is protected within the bone structure formed by the skull bones. The nervous system and endocrine system play a fundamental role in maintaining brain homeostasis. The brain; How are the wastes that occur as a result of these biochemical events eliminated when it has such basic and important tasks? Until 2012, it was thought that there was no lymphatic system in the brain. Our aim with this literature review is to make it easier to find answers to these questions. Materials and Methods: For this review research, the existing literature was systematically reviewed in terms of the glymphatic system. Results: The glymphatic system is the brain’s waste clearance mechanism. Many anatomical structures are involved in the glymphatic system. Astrocytes and aquaporin-4 channels were the most notable of these. Conclusions: The glymphatic system is a waste clearing mechanism in the brain that has many important function mechanisms. Although it has been the subject of current research with human and animal experiments in recent years, it is still an area that preserves its mystery. Although it has been the subject of current research with human and animal experiments in recent years, it is still an area that remains mysterious. Disruption of this system is closely associated with neurodegenerative diseases. We believe that this system, which plays a vital role in brain health, should be the subject of more scientific research to clarify its functioning mechanism.

Keywords

• Brain
• Lymphatic System
• Neurodegenerative diseases
• Neuroanatomy

References

1. 1. Çelik M. Lenfatik sistem tarihçesi’ne yolculuk: keşifler ve gelişmeler. Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi. 2023;13(3):529-42.
2. 2. Hablitz LM, Nedergaard M. The glymphatic system. Curr Biol. 2021;31(20):R1371-5.
3. 3. Oliver G, Kipnis J, Randolph GJ, Harvey NL. 21. yüzyılda lenf damar sistemi: Homeostaz ve hastalıkta yeni işlevsel roller. Cell. 2020;182:270-96.
4. 4. Ang PS, Zhang DM, Azizi SA, Norton de Matos SA, Brorson JR. The glymphatic system and cerebral small vessel disease. J Stroke Cerebrovasc Dis. 2024;33(3):107557.
5. 5. Shetty AK, Zanirati G. The interstitial system of the brain in health and disease. Aging Dis. 2020;11(1):200-11.
6. 6. Li Y, Han H, Shi K, Cui D, Yang J, Alberts IL, et al. The mechanism of downregulated interstitial fluid drainage following neuronal excitation. Aging Dis. 2020;11(6):1407-22.
7. 7. Yang T, Sun Y, Li Q, Alraqmany N, Zhang F. Effects of ischemic stroke on interstitial fluid clearance in mouse brain: A bead study. Cell Mol Neurobiol. 2023;43(8):4141-56.
8. 8. Pham C, Komaki Y, Deàs-Just A, Le Gac B, Mouffle C, Franco C, et al. Astrocyte aquaporin mediates a tonic water efflux maintaining brain homeostasis. Elife. 2024;13:RP95873.

9. 9. Jiang H, Wei H, Zhou Y, Xiao X, Zhou C, Ji X. Overview of the meningeal lymphatic vessels in aging and central nervous system disorders. Cell Biosci. 2022;12(1):202.
10. 10. Chachaj A, Gąsiorowski K, Szuba A, Sieradzki A, Leszek J. The lymphatic system in the brain clearance mechanisms - New therapeutic perspectives for Alzheimer’s disease. Curr Neuropharmacol. 2023;21(2):380-91.
11. 11. Kroesbergen E, Riesselmann LV, Gomolka RS, Plá V, Esmail T, Stenmo VH, et al. Glymphatic clearance is enhanced during sleep. bioRxiv [Preprint]. 2024. https://doi.org/10.1101/2024.08.
12. 12. Taş F, Erdoğan E. Sıçan ependim hücrelerinde aquaporin 4 kanallarının immünohistokimyasal dağılımı ve glimfatik sisteme etkisi. Ahi Evran Med J. 2020;4(2):41-6.
13. 13. Deng S, Hu Y, Chen S, Xue Y, Yao D, Sun Q, et al. Chronic sleep fragmentation impairs brain interstitial clearance in young wildtype mice. J Cereb Blood Flow Metab. 2024;44(9):1515-31.
14. 14. Vasciaveo V, Iadarola A, Casile A, Dante D, Morello G, Minotta L, et al. Sleep fragmentation affects glymphatic system through the different expression of AQP4 in wild type and 5xFAD mouse models. Acta Neuropathol Commun. 2023;11(1):16.
15. 15. Wang J, Tian Y, Qin C, Meng L, Feng R, Xu S, et al. Impaired glymphatic drainage underlying obstructive sleep apnea is associated with cognitive dysfunction. J Neurol. 2023;270(4):2204-16.
16. 16. Akbulut NH, Topal G, Eyigör Ö. İskemik beyin hasarında reaktif astrositlerin fonksiyonları. Uludag Univ Tip Fak Derg. 2023;49(1):133-43.
17. 17. Özen NPA, Bektaş H, Tuncer A. İmmünolojik bakış açısı ile uyku ve astrositler. Turkiye Klin Bilimsel Oturumlar. 2020;2(1):86-92.
18. 18. Wikipedia. Astrocyte. https://en.wikipedia.org/wiki/Astrocyte. Erişim: 12 Şubat 2025.
19. 19. Xiong Y, Yu Q, Zhi H, Peng H, Xie M, Li R, et al. Advances in the study of the glymphatic system and aging. CNS Neurosci Ther. 2024;30(6):e14803.
20. 20. Cullell N, Caruana G, Elias-Mas A, Delgado-Sanchez A, Artero C, Buongiorno MT, et al. Glymphatic system clearance and Alzheimer’s disease risk: A CSF proteome-wide study. Alzheimers Res Ther. 2025;17(1):31.
21. 21. Bonnar O, Eyre B, van Veluw SJ. Perivascular brain clearance as a therapeutic target in cerebral amyloid angiopathy and Alzheimer’s disease. Neurotherapeutics. 2025. e00535.
22. 22. Ren J, Xie D, Wang L, Wu Z, Lin S, Jin Q, et al. Glymphatic system dysfunction as a biomarker of disease progression in Parkinson’s disease: Neuroimaging evidence from longitudinal cohort studies. J Neurol. 2025;272(3):196.
23. 23. Wang X, Huang P, Haacke EM, Wu P, Zhang X, Zhang H, et al. MRI index of glymphatic system mediates the influence of locus coeruleus on cognition in Parkinson’s disease. Parkinsonism Relat Disord. 2024;123:106558.
24. 24. Zhou C, Jiang X, Guan X, Guo T, Wu J, Wu H, et al. Glymphatic system dysfunction and risk of clinical milestones in patients with Parkinson disease. Eur J Neurol. 2024;31(12):e16521.
25. 25. Michalaki E, Pulliam AN, Datta Roy PM, Dixon JB, LaPlaca MC. Near-infrared imaging of glymphatic clearance in a pre-clinical model of repetitive closed head traumatic brain injury. Neurotrauma Rep. 2025;6(1):115-28.
26. 26. Alghanimy A, Work LM, Holmes WM. The glymphatic system and multiple sclerosis: An evolving connection. Mult Scler Relat Disord. 2024;83:105456.
27. 27. Tomizawa Y, Hagiwara A, Hoshino Y, Nakaya M, Kamagata K, Cossu D, et al. The glymphatic system as a potential biomarker and therapeutic target in secondary progressive multiple sclerosis. Mult Scler Relat Disord. 2024;83:105437.
28. 28. Valdes-Hernandez PA, Montesino-Goicolea S, Nodarse CL, Johnson AJ, Fillingim RB, Cruz-Almeida Y. Widespread and prolonged pain may reduce brain clearance capacity only via sleep impairment: Evidence from participants with knee pain. J Pain. 2025;30:105356.
29. 29. Finkelstein AJ, Sipple MT, Akkipeddi SM, White R, Kohli GS, Susa S, et al. Glymphatic flow after thrombectomy is associated with futile recanalization in large vessel occlusion stroke. medRxiv [Preprint]. 2025. https://doi.org/10.1101/2025.XX.XX
30. 30. Zhu J, Mo J, Liu K, Chen Q, Li Z, He Y, et al. Glymphatic system impairment contributes to the formation of brain edema after ischemic stroke. Stroke. 2024;55(5):1393-404.
31. 31. Wang L, Hu J, Li JX, Tan Z, Wang FY, Wu JC. Association between glymphatic system function and cognitive impairment in elderly patients with late-onset epilepsy. Epilepsy Behav. 2025;164:110258.
32. 32. Jin B, Xu J, Hu J, Li H, Wang S, Chen C, et al. Glymphatic system dysfunction in epilepsy related to focal cortical dysplasia and its relationship with antiseizure medication response. Seizure. 2025;125:31-6.
33. 33. Villacis G, Schmidt A, Rudolf JC, Schwenke H, Küchler J, Schramm P, et al. Evaluating the glymphatic system via magnetic resonance diffusion tensor imaging along the perivascular spaces in brain tumor patients. Jpn J Radiol. 2024;42(10):1146-56.
34. 34. Bao W, Jiang P, Xu P, Lin H, Xu J, Lai M, et al. Lower DTI-ALPS index in patients with major depressive disorder: Correlation with fatigue. Behav Brain Res. 2025;478:115323.
35. 35. Lee HJ, Lee DA, Park KM. Choroid plexus enlargement in patients with chronic migraine: Implications for glymphatic system dysfunction. Can J Neurol Sci. 2025;1-18.
36. 36. Duan S, Hu J. Pathogenesis and management of low-pressure hydrocephalus: A narrative review. J Neurol Sci. 2024;122988.
37. 37. Zang X, Chen S, Zhu J, Ma J, Zhai Y. The emerging role of central and peripheral immune systems in neurodegenerative diseases. Front Aging Neurosci. 2022;14:872134.
38. 38. Olegário RL, Nóbrega OT, Camargos EF. The newly discovered glymphatic system: The missing link between physical exercise and brain health? Front Integr Neurosci. 2024;18:1349563.
39. 39. Duan S, Hu J. Pathogenesis and management of low-pressure hydrocephalus: A narrative review. J Neurol Sci. 2024;122988.
40. 40. Zang X, Chen S, Zhu J, Ma J, Zhai Y. The emerging role of central and peripheral immune systems in neurodegenerative diseases. Front Aging Neurosci. 2022;14:872134.
41. 41. Olegário RL, Nóbrega OT, Camargos EF. The newly discovered glymphatic system: The missing link between physical exercise and brain health? Front Integr Neurosci. 2024;18:1349563.
42. 42. Liang S, Liu H, Wang X, Lin H, Zheng L, Zhang Y, et al. Aerobic exercise improves clearance of amyloid-β via the glymphatic system in a mouse model of Alzheimer’s disease. Brain Res Bull. 2025;222:111263.