Pathobiology of the Glymphatic System in the Traumatic Brain Injury: A Narrative Review
Juan Jose Beltran-Ruiz, Juan Sebastian Reyes-Bello, Claudia Marcela Restrepo-Lugo
Keywords :
Brain trauma, Craniocerebral trauma, Glymphatic system
Citation Information :
Beltran-Ruiz JJ, Reyes-Bello JS, Restrepo-Lugo CM. Pathobiology of the Glymphatic System in the Traumatic Brain Injury: A Narrative Review. Panam J Trauma Crit Care Emerg Surg 2022; 11 (2):82-87.
The glymphatic system (GS) is responsible in the brain for transporting substances toward the interstitium and then out of it; it is essential for neuronal functioning and even more so after any brain injury.
It is a fragile system, its functioning is altered with age, sleep disorders, and neuronal damage as in head trauma, causing a decrease in the clearance of neurotoxic and inflammatory substances, which triggers neurodegeneration and alterations in neuro repair, despite having different mechanisms that allow the flow of nutrients and clearance of harmful substances for neuronal survival and rehabilitation.
This article describes the relationship between head trauma and dysfunction of the GS, as well as the negative effects on the brain parenchyma and secondary neuroinflammation. This system is not only affected by the change in the “polarization” of the aquaporin (AQP) four channels of the astrocytes but also by the characteristics of the substances in the neuronal environment, that opt for a different transport mechanism from the GS.
Piantino J, Lim MM, Newgard CD, et al. Linking traumatic brain injury, sleep disruption and post-traumatic headache: a potential role for glymphatic pathway dysfunction. Curr Pain Headache Rep 2019;23(9):62. DOI: 10.1007/s11916-019-0799-4
Xiong Y, Mahmood A, Chopp M. Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities. Chin J Traumatol 2018;21(3):137–151. DOI: 10.1016/j.cjtee.2018.02.003
Plog BA, Nedergaard M. The glymphatic system in central nervous system health and disease: past, present, and future. Annu Rev Pathol 2018;13:379–394. DOI: 10.1146/annurev-pathol-051217-111018
Nagelhus EA, Ottersen OP. Physiological roles of aquaporin-4 in brain. Physiol Rev 2013;93(4):1543–1562. DOI: 10.1152/physrev.00011.2013
Meyerhoff J, Chakraborty N, Hammamieh R. Glymphatics: a transformative development in medical neuroscience relevant to injuries in military central nervous system. Mil Med 2021;usab344. DOI: 10.1093/milmed/usab344
May R, Reddy U. Cerebrospinal fluid and its physiology. Anaesth Intensive Care Med 2020;21(1):60–61. DOI: 10.1016/j.mpaic.2019.10.017
Louveau A, Plog BA, Antila S, et al. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. J Clin Invest 2017;127(9):3210–3219. DOI: 10.1172/JCI90603
Martin BA, Heidari Pahlavian S. Chapter 5 - Anatomy and physiology of cerebrospinal fluid dynamics. In: Lonser RR, Sarntinoranont M, Bankiewicz K, editors. Nervous System Drug Delivery: Academic Press; 2019:73–89. DOI: 10.1016/B978-0-12-813997-4.00005-0
Breslin JW, Yang Y, Scallan JP, et al. Lymphatic Vessel network structure and physiology. Compr Physiol 2018;9(1):207–299. DOI: 10.1002/cphy.c180015
Mogensen FL, Delle C, Nedergaard M. The glymphatic system (En)during inflammation. Int J Mol Sci 2021;22(14):7491. DOI: 10.3390/ijms22147491
Iliff JJ, Nedergaard M. Is there a cerebral lymphatic system? Stroke 2013;44(6 Suppl 1):S93–S95. DOI: 10.1161/STROKEAHA.112.678698
Da Mesquita S, Fu Z, Kipnis J. The Meningeal lymphatic system: a new player in neurophysiology. Neuron 2018;100(2):375–388. DOI: 10.1016/j.neuron.2018.09.022
Li L, Chopp M, Ding G, et al. MRI detection of impairment of glymphatic function in rat after mild traumatic brain injury. Brain Res 2020;1747:147062. DOI: 10.1016/j.brainres.2020.147062
Taoka T, Masutani Y, Kawai H, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases. Jpn J Radiol 2017;35(4):172–178. DOI: 10.1007/s11604-017-0617-z
Nedergaard M. Neuroscience. Garbage truck of the brain. Science 2013;340(6140):1529–1530. DOI: 10.1126/science.1240514
Ringstad G, Valnes LM, Dale AM, et al. Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. JCI Insight 2018;3(13):e121537. DOI: 10.1172/jci.insight.121537
Eide PK, Vatnehol SAS, Emblem KE, et al. Magnetic resonance imaging provides evidence of glymphatic drainage from human brain to cervical lymph nodes. Sci Rep 2018;8(1):7194. DOI: 10.1038/s41598-018-25666-4
Eide PK, Mariussen E, Uggerud H, et al. Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood. JCI Insight 2021;6(9):e147063. DOI: 10.1172/jci.insight.147063
Eide PK, Ringstad G. MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain. Acta Radiol Open 2015;4(11): 2058460115609635. DOI: 10.1177/2058460115609635
Ringstad G, Vatnehol SAS, Eide PK. Glymphatic MRI in idiopathic normal pressure hydrocephalus. Brain 2017;140(10):2691–2705. DOI: 10.1093/brain/awx191
Eide PK, Pripp AH, Ringstad G. Magnetic resonance imaging biomarkers of cerebrospinal fluid tracer dynamics in idiopathic normal pressure hydrocephalus. Brain Commun 2020;2(2):fcaa187. DOI: 10.1093/braincomms/fcaa187
Edeklev CS, Halvorsen M, Løvland G, et al. Intrathecal use of gadobutrol for glymphatic MR imaging: prospective safety study of 100 patients. AJNR Am J Neuroradiol 2019;40(8):1257–1264. DOI: 10.3174/ajnr.A6136
Roncali L, Virgintino D, Coltey P, et al. Morphological aspects of the vascularization in intraventricular neural transplants from embryo to embryo. Anat Embryol (Berl) 1996;193(3):191–203. DOI: 10.1007/BF00198323
Hauglund NL, Kusk P, Kornum BR, et al. Meningeal lymphangiogenesis and enhanced glymphatic activity in mice with chronically implanted EEG electrodes. J Neurosci 2020;40(11):2371–2380. DOI: 10.1523/JNEUROSCI.2223-19.2020
Jessen NA, Munk AS, Lundgaard I, et al. The glymphatic system: a beginner's guide. Neurochem Res 2015;40(12):2583–2599. DOI: 10.1007/s11064-015-1581-6
Lucke-Wold BP, Smith KE, Nguyen L, et al. Sleep disruption and the sequelae associated with traumatic brain injury. Neurosci Biobehav Rev 2015;55:68–77. DOI: 10.1016/j.neubiorev.2015.04.010
Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science 2013;342(6156):373–377. DOI: 10.1126/science.1241224
Lee H, Xie L, Yu M, et al. The Effect of body posture on brain glymphatic transport. J Neurosci 2015;35(31):11034–11044. DOI: 10.1523/JNEUROSCI.1625-15.2015
Fuxe K, Agnati LF, Marcoli M, et al. Volume transmission in central dopamine and noradrenaline neurons and its astroglial targets. Neurochem Res 2015;40(12):2600–2614. DOI: 10.1007/s11064-015-1574-5
Kiviniemi V, Wang X, Korhonen V, et al. Ultra-fast magnetic resonance encephalography of physiological brain activity - glymphatic pulsation mechanisms? J Cereb Blood Flow Metab 2016;36(6):1033–1045. DOI: 10.1177/0271678X15622047
Rajna Z, Kananen J, Keskinarkaus A, et al. Detection of short-term activity avalanches in human brain default mode network with ultrafast MR encephalography. Front Hum Neurosci 2015;9:448. DOI: 10.3389/fnhum.2015.00448
Sullan MJ, Asken BM, Jaffee MS, et al. Glymphatic system disruption as a mediator of brain trauma and chronic traumatic encephalopathy. Neurosci Biobehav Rev 2018;84:316–324. DOI: 10.1016/j.neubiorev.2017.08.016
Hsieh CL, Niemi EC, Wang SH, et al. CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury. J Neurotrauma 2014;31(20):1677–1688. DOI: 10.1089/neu.2013.3252
Arguello J. TCE - Traumatismo craneoencefálico Foro Iberoamericano de discusiones sobre la Familia de Clasificaciones Internacionales de la OMS (FCI-OMS) 2018 [Available from: https://www3.paho.org/relacsis/index.php/es/foros-relacsis/foro-becker-fci-oms/61-foros/consultas-becker/938-tce-traumatismo-craneoencefalicohttps://www3pahoorg/relacsis/index.php/es/foros-relacsis/foro-becker-fci-oms/61-foros/consultas-becker/938-tce-traumatismo-craneoencefalico.
Simon DW, McGeachy MJ, Bayir H, et al. The far-reaching scope of neuroinflammation after traumatic brain injury. Nat Rev Neurol 2017;13(3):171–191. DOI: 10.1038/nrneurol.2017.13
Bolte AC, Lukens JR. Neuroimmune cleanup crews in brain injury. Trends Immunol 2021;42(6):480–494. DOI: 10.1016/j.it.2021.04.003
Christensen J, Wright DK, Yamakawa GR, et al. Repetitive Mild traumatic brain injury alters glymphatic clearance rates in limbic structures of adolescent female rats. Sci Rep 2020;10(1):6254. DOI: 10.1038/s41598-020-63022-7
Killen MJ, Giorgi-Coll S, Helmy A, et al. Metabolism and inflammation: implications for traumatic brain injury therapeutics. Expert Rev Neurother 2019;19(3):227–242. DOI: 10.1080/14737175.2019.1582332
Lv T, Zhao B, Hu Q, et al. The glymphatic system: a novel therapeutic target for stroke treatment. Front Aging Neurosci 2021;13:689098. DOI: 10.3389/fnagi.2021.689098
Iliff JJ, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 2012;4(147):147ra111. DOI: 10.1126/scitranslmed.3003748
Christensen J, Yamakawa GR, Shultz SR, et al. Is the glymphatic system the missing link between sleep impairments and neurological disorders? Examining the implications and uncertainties. Prog Neurobiol 2021;198:101917. DOI: 10.1016/j.pneurobio.2020.101917
Smith AJ, Yao X, Dix JA, et al. Test of the ‘glymphatic’ hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma. Elife 2017;6:e27679. DOI: 10.7554/eLife.27679
Mestre H, Mori Y, Nedergaard M. The brain's glymphatic system: current controversies. Trends Neurosci 2020;43(7):458–466. DOI: 10.1016/j.tins.2020.04.003
Koundal S, Elkin R, Nadeem S, et al. Optimal mass transport with Lagrangian Workflow reveals advective and diffusion driven solute transport in the glymphatic system. Sci Rep 2020;10(1):1990. DOI: 10.1038/s41598-020-59045-9
Ray L, Iliff JJ, Heys JJ. Analysis of convective and diffusive transport in the brain interstitium. Fluids Barriers CNS 2019;16(1):6. DOI: 10.1186/s12987-019-0126-9
Ren Z, Iliff JJ, Yang L, et al. ‘Hit & Run’ model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation. J Cereb Blood Flow Metab 2013;33(6):834–845. DOI: 10.1038/jcbfm.2013.30
Iliff JJ, Chen MJ, Plog BA, et al. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci 2014;34(49):16180–93. DOI: 10.1523/JNEUROSCI.3020-14.2014
Cherian I, Burhan H, Dashevskiy G, et al. Cisternostomy: a timely intervention in moderate to severe traumatic brain injuries: rationale, indications, and prospects. World Neurosurg 2019;131:385–390. DOI: 10.1016/j.wneu.2019.07.082
Cherian I, Bernardo A, Grasso G. Cisternostomy for Traumatic brain injury: pathophysiologic mechanisms and surgical technical notes. World Neurosurg 2016;89:51–57. DOI: 10.1016/j.wneu.2016.01.072
Kanmounye US. The rise of inflow cisternostomy in resource-limited settings: rationale, limitations, and future challenges. Emerg Med Int 2021;2021:6630050. DOI: 10.1155/2021/6630050
Cherian I, Yi G, Munakomi S. Cisternostomy: replacing the age old decompressive hemicraniectomy? Asian J Neurosurg 2013;8(3):132–138. DOI: 10.4103/1793-5482.121684
Henry RJ, Ritzel RM, Barrett JP, et al. Microglial depletion with CSF1R Inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits. J Neurosci 2020;40(14):2960–2974. DOI: 10.1523/JNEUROSCI.2402-19.2020
Kratz SV. Case report: manual therapies promote resolution of persistent post-concussion symptoms in a 24-year-old athlete. SAGE Open Med Case Rep 2021;9:2050313X20952224. DOI: 10.1177/2050313X20952224
Peng W, Achariyar TM, Li B, et al. Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease. Neurobiol Dis 2016;93:215–225. DOI: 10.1016/j.nbd.2016.05.015
Doustar J, Danan IJ. Glymphatic system dysfunction in mild traumatic brain injury. Neurology 2022;98(1 Supplement 1):S24. DOI: 10.1212/01.wnl.0000801968.87371.4e