Effects of Stress on the Brain’s Glymphatic System

Main Article Content

Mariya Ivanovska
Meral Naimova
Marianna Murdjeva

Abstract

Psychoneuroendocrine immunology is an integrated field that explores the pathways through which psychological experiences influence immune function and how the immune system, in turn, might alter brain function. The glial-lymphatic system regulates fluid balance and waste removal in the central nervous system, which lacks an independent lymphatic system (glymphatic system). We looked for literature on stress, its consequences, and the glymphatic system in PubMed/MEDLINE, Google Scholar, Scopus, and other online databases. Work, examinations, physical, and mental stress brought on by sickness, trauma, and other everyday occurrences are just a few examples of situations that might be categorized as “stressful.” The “fight-flight-freeze response” is the name given to the body’s combination of adaptations in reaction to stress. Sleep problems are associated with higher levels of stress. It is plausible to assume that this is the mechanism through which stress affects glymphatic function given that the brain’s waste disposal system has been shown to be active during sleep. Studying whether stress reduction can enhance brain waste removal and the prognosis of illnesses marked by metabolite accumulation is promising.

Downloads

Download data is not yet available.

Plum Analytics

Article Details

How to Cite
1.
Ivanovska M, Naimova M, Murdjeva M. Effects of Stress on the Brain’s Glymphatic System. SEE J Immunol [Internet]. 2023 Aug. 17 [cited 2024 May 20];6(1):70-9. Available from: https://seejim.eu/index.php/seejim/article/view/6040
Section
Basic Immunology

References

Trevaskis NL, Kaminskas LM, Porter CJ. From sewer to saviour - targeting the lymphatic system to promote drug

exposure and activity. Nat Rev Drug Discov. 2015;14(11):781-803. https://doi.org/10.1038/nrd4608 PMid:26471369

Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The glymphatic system: A Beginner’s guide. Neurochem Res. 2015;40(12):2583-99. https://doi.org/10.1007/s11064-015-1581-6 PMid:25947369

Bacyinski A, Xu M, Wang W, Hu J. The paravascular pathway for brain waste clearance: Current understanding, significance and controversy. Front Neuroanat. 2017;11:101. https://doi.org/10.3389/fnana.2017.00101 PMid:29163074

McEwen BS. Protective and damaging effects of stress mediators: Central role of the brain. Dialogues Clin Neurosci. 2006;8(4):367-81. https://doi.org/10.31887/DCNS.2006.8.4/bmcewen PMid:17290796

Weller RO, Subash M, Preston SD, Mazanti I, Carare RO. Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol. 2008;18(2):253-66. https://doi.org/10.1111/j.1750-3639.2008.00133.x PMid:18363936

Carare RO, Bernardes-Silva M, Newman TA, Page AM, Nicoll JA, Perry VH, et al. Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: Significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol. 2008;34(2):131-44. https://doi.org/10.1111/j.1365-2990.2007.00926.x PMid:18208483

Hawkes CA, Härtig W, Kacza J, Schliebs R, Weller RO, Nicoll JA, et al. Perivascular drainage of solutes is impaired in the aging mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol. 2011;121(4):431-43. https://doi.org/10.1007/s00401-011-0801-7 PMid:21259015

Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, 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. https://doi.org/10.1126/scitranslmed.3003748 PMid:22896675

Murtha LA, Yang Q, Parsons MW, Levi CR, Beard DJ, Spratt NJ, et al. Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats. Fluids Barriers CNS. 2014;11:12. https://doi.org/10.1186/2045-8118-11-12 PMid:24932405

Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, et al. Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol. 2015;11(8):457-70. https://doi.org/10.1038/nrneurol.2015.119 PMid:26195256

Simon MJ, Iliff JJ. Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease. Biochim Biophys Acta. 2016;1862(3):442-51. https://doi.org/10.1016/j.bbadis.2015.10.014 PMid:26499397

Lundgaard I, Lu ML, Yang E, Peng W, Mestre H, Hitomi E, et al. Glymphatic clearance controls state- dependent changes in brain lactate concentration. J Cereb Blood Flow Metab. 2017;37(6):2112-24. https://doi.org/10.1177/0271678X16661202 PMid:27481936

Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, Yang L, et al. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci. 2014;34(49):16180-93. https://doi.org/10.1523/JNEUROSCI.3020-14.2014 PMid:25471560

Matsumae M, Atsumi H, Hirayama A, Hayashi N, Sano F, Taiozawa K, et al. A new look at cerebrospinal fluid motion. No Shinkei Geka. 2016;44:909-24.

Achariyar TM, Li B, Peng W, Verghese PB, Shi Y, McConnell E, et al. Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation. Mol Neurodegener. 2016;11(1):74.

Rangroo Thrane V, Thrane AS, Plog BA, Thiyagarajan M, Iliff JJ, Deane R, et al. Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain. Sci Rep. 2013;3:2582. https://doi.org/10.1038/srep02582 PMid:24002448

Kress BT, Iliff JJ, Xia M, Wang M, Wei HS, Zeppenfeld D, et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76(6):845-61. https://doi.org/10.1002/ana.24271 PMid:25204284

Sullan MJ, Asken BM, Jaffee MS, DeKosky ST, Bauer RM. Glymphatic system disruption as a mediator of brain trauma and chronic traumatic encephalopathy. Neurosci Biobehav Rev. 2018;84:316-24. https://doi.org/10.1016/j.neubiorev.2017.08.016 PMid:28859995

Benveniste H, Liu X, Koundal S, Sanggaard S, Lee H, Wardlaw J. The glymphatic system and waste clearance with brain aging: A review. Gerontology. 2019;65(2):106-19. https://doi.org/10.1159/000490349 PMid:29996134

Wei F, Song J, Zhang C, Lin J, Xue R, Shan LD, et al. Chronic stress impairs the aquaporin-4-mediated glymphatic transport through glucocorticoid signaling. Psychopharmacology (Berl). 2019;236(4):1367-84. https://doi.org/10.1007/s00213-018-5147-6 PMid:30607477

Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev. 2000;21(1):55-89. https://doi.org/10.1210/edrv.21.1.0389 PMid:10696570

Bernstein R. The Mind and Mental Health: How Stress Affects the Brain. California: Touro University Worldwide; 2016.

McEwen BS, Bowles NP, Gray JD, Hill MN, Hunter RG, Karatsoreos IN, et al. Mechanisms of stress in the brain. Nat Neurosci. 2015;18(10):1353-63. https://doi.org/10.1038/nn.4086 PMid:26404710

Horner HC, Packan DR, Sapolsky RM. Glucocorticoids inhibit glucose transport in cultured hippocampal neurons and glia. Neuroendocrinology. 1990;52(1):57-64. https://doi.org/10.1159/000125539 PMid:2118608

Virgin CE Jr., Ha TP, Packan DR, Tombaugh GC, Yang SH, Horner HC, et al. Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: Implications for glucocorticoid neurotoxicity. J Neurochem. 1991;57(4):1422-8. https://doi.org/10.1111/j.1471-4159.1991.tb08309.x PMid:1680166

Doyle P, Guillaume-Gentil C, Rohner-Jeanrenaud F, Jeanrenaud B. Effects of corticosterone administration on local cerebral glucose utilization of rats. Brain Res. 1994; 645(1-2):225-30.https://doi.org/10.1016/0006-8993(94)91655-1 PMid:8062085

Sapolsky RM. Why stress is bad for your brain. Science. 1996;273(5276):749-50. https://doi.org/10.1126/science.273.5276.749 PMid:8701325

Newcomer JW, Craft S, Hershey T, Askins K, Bardgett ME. Glucocorticoid-induced impairment in declarative memory performance in adult humans. J Neurosci. 1994;14(4):2047-53. https://doi.org/10.1523/JNEUROSCI.14-04-02047.1994 PMid:8198631

Brady KT, Sonne SC. The role of stress in alcohol use, alcoholism treatment, and relapse. Alcohol Res Health. 1999;23(4):263-71.

Lundgaard I, Wang W, Eberhardt A, Vinitsky HS, Reeves C, Peng S, et al. Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function. Sci Rep. 2018;8(1):2246. https://doi.org/10.1038/s41598-018-20424-y PMid:29396480

Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373-7. https://doi.org/10.1126/science.1241224 PMid:24136970

Kalimo R, Tenkanen L, Härmä M, Poppius E, Heinsalmi P. Job stress and sleep disorders: Findings from the Helsinki Heart Study. Stress Med. 2000;16(2):65-75.

Akerstedt T, Kecklund G, Axelsson J. Impaired sleep after bedtime stress and worries. Biol Psychol. 2007;76(3):170-3. https://doi.org/10.1016/j.biopsycho.2007.07.010 PMid:17884278

Bernardy NC, Friedman MJ. A Practical Guide to PTSD Treatment: Pharmacological and Psychotherapeutic Approaches. A Practical Guide to PTSD Treatment: Pharmacological and Psychotherapeutic Approaches. United States: American Psychological Association; 2014.

Jansen AS, Van Nguyen X, Karpitskiy V, Mettenleiter TC, Loewy AD. Central command neurons of the sympathetic nervous system: Basis of the fight-or-flight response. Science. 1995;270(5236):644-6.

McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998;338(3):171-9. https://doi.org/10.1056/NEJM199801153380307 PMid:9428819

Lindquist TL, Beilin LJ, Knuiman MW. Influence of lifestyle, coping, and job stress on blood pressure in men and women. Hypertension. 1997;29(1 Pt 1):1-7. https://doi.org/10.1161/01. hyp.29.1.1 PMid:9039072

Kaplan JR, Manuck SB, Clarkson TB, Lusso FM, Taub DM, Miller EW. Social stress and atherosclerosis in normocholesterolemic monkeys. Science. 1983;220(4598):733-5. https://doi.org/10.1126/science.6836311 PMid:6836311

Dallman MF. Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab. 2010;21(3):159-65. https://doi.org/10.1016/j.tem.2009.10.004 PMid:19926299

Hammen C. Stress and depression. Annu Rev Clin Psychol. 2005;1:293-319. https://doi.org/10.1146/annurev.clinpsy.1.102803.143938 PMid:17716090

Goeders NE. The impact of stress on addiction. Eur Neuropsychopharmacol. 2003;13(6):435-41. https://doi.org/10.1016/j.euroneuro.2003.08.004 PMid:14636959

Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35(1): 169-91. https://doi.org/10.1038/npp.2009.83 PMid:19625997

Berridge CW, Waterhouse BD. The locus coeruleus- noradrenergic system: Modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev. 2003;42(1):33-84. https://doi.org/10.1016/s0165-0173(03)00143-7 PMid:12668290

O’Donnell J, Ding F, Nedergaard M. Distinct functional states of astrocytes during sleep and wakefulness: Is norepinephrine the master regulator? Curr Sleep Med Rep. 2015;1(1):1-8. https://doi.org/10.1007/s40675-014-0004-6 PMid:26618103

Lee H, Xie L, Yu M, Kang H, Feng T, Deane R, et al. The Effect of body posture on brain glymphatic transport. J Neurosci. 2015;35(31):11034-44. https://doi.org/10.1523/JNEUROSCI.1625-15.2015 PMid:26245965

Akerstedt T. Psychosocial stress and impaired sleep. Scand J Work Environ Health 2006;32(6):493-501.

Fu H, Hardy J, Duff KE. Selective vulnerability in neurodegenerative diseases. Nat Neurosci. 2018;21(10): 1350-8. https://doi.org/10.1038/s41593-018-0221-2 PMid:30250262

Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med. 2004;10 Suppl: S10-7. http://doi.org/10.1038/nm1066 PMid:15272267

Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci. 1991;12(10):383-8. https://doi.org/10.1016/0165-6147(91)90609-v PMid:1763432

Peng W, Achariyar TM, Li B, Liao Y, Mestre H, Hitomi E, et al. Suppression of glymphatic fluid transport in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2016;93:215-25. https://doi.org/10.1016/j.nbd.2016.05.015 PMid:27234656

Zuroff L, Daley D, Black KL, Koronyo-Hamaoui M. Clearance of cerebral Aβ in Alzheimer’s disease: Reassessing the role of microglia and monocytes. Cell Mol Life Sci. 2017;74(12):2167-201. https://doi.org/10.1007/s00018-017-2463-7 PMid:28197669

Qi XM, Ma JF. The role of amyloid beta clearance in cerebral amyloid angiopathy: More potential therapeutic targets. Transl Neurodegener. 2017;6:22. https://doi.org/10.1186/s40035-017-0091-7 PMid:28824801

Wang LY, Murphy RR, Hanscom B, Li G, Millard SP, Petrie EC, et al. Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span. Neurobiol Aging. 2013;34(10):2287-92. https://doi.org/10.1016/j.neurobiolaging.2013.04.007 PMid:23639207

Szot P. Elevated cerebrospinal fluid norepinephrine in the elderly can link depression and a reduced glymphatic system as risk factors for Alzheimer’s Disease. J Aging Sci. 2016;4(2):158.

Musiek ES, Xiong DD, Holtzman DM. Sleep, circadian rhythms, and the pathogenesis of Alzheimer’s disease. Exp Mol Med. 2015;47(3):e148. https://doi.org/10.1038/emm.2014.121 PMid:25766617

Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018;17(11):1016-24. https://doi.org/10.1016/S1474-4422(18)30318-1 PMid:30353860

Mendelsohn AR, Larrick JW. Sleep facilitates clearance of metabolites from the brain: Glymphatic function in aging and neurodegenerative diseases. Rejuvenation Res. 2013;16(6):518-23. https://doi.org/10.1089/rej.2013.1530 PMid:24199995

Piantino J, Lim MM, Newgard CD, Iliff J. 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. https://doi.org/10.1007/s11916-019-0799-4 PMid:31359173

Gaberel T, Gakuba C, Goulay R, De Lizarrondo SM, Hanouz JL, Emery E, et al. Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: A new target for fibrinolysis? Stroke. 2014;45(10):3092-6. https://doi.org/10.1161/STROKEAHA.114.006617 PMid:25190438

Back DB, Kwon KJ, Choi DH, Shin CY, Lee J, Han SH, et al. Chronic cerebral hypoperfusion induces post-stroke dementia following acute ischemic stroke in rats. J Neuroinflammation. 2017;14(1):216. https://doi.org/10.1186/s12974-017-0992-5 PMid:29121965

Bobela W, Aebischer P, Schneider BL. Αlpha-synuclein as a mediator in the interplay between aging and Parkinson’s disease. Biomolecules. 2015;5(4):2675-700. https://doi.org/10.3390/biom5042675 PMid:26501339

Zou W, Pu T, Feng W, Lu M, Zheng Y, Du R, et al. Blocking meningeal lymphatic drainage aggravates Parkinson’s disease- like pathology in mice overexpressing mutated α-synuclein. Transl Neurodegener. 2019;8:7. https://doi.org/10.1186/s40035-019-0147-y PMid:30867902

Sundaram S, Hughes RL, Peterson E, Müller-Oehring EM, Brontë-Stewart HM, Poston KL, et al. Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease. Neurosci Biobehav Rev. 2019;103:305-15. https://doi.org/10.1016/j.neubiorev.2019.05.016 PMid:31132378

Jiang Q, Zhang L, Ding G, Davoodi-Bojd E, Li Q, Li L, et al. Impairment of the glymphatic system after diabetes. J Cereb Blood Flow Metab. 2017;37(4):1326-37. https://doi.org/10.1177/0271678X16654702 PMid:27306755

Hirotsu C, Tufik S, Andersen ML. Interactions between sleep, stress, and metabolism: From physiological to pathological conditions. Sleep Sci. 2015;8(3):143-52. https://doi.org/10.1016/j.slsci.2015.09.002 PMid:26779321

Vasileva LV, Saracheva KE, Ivanovska MV, Petrova AP, Marchev AS, Georgiev MI, et al. Antidepressant-like effect of salidroside and curcumin on the immunoreactivity of rats subjected to a chronic mild stress model. Food Chem Toxicol. 2018;121:604-11. https://doi.org/10.1016/j.fct.2018.09.065 PMid:30268794

Dhabhar FS. Enhancing versus suppressive effects of stress on immune function: Implications for immunoprotection and immunopathology. Neuroimmunomodulation. 2009;16(5):300-17. https://doi.org/10.1159/000216188 PMid:19571591

Williams RB, Marchuk DA, Gadde KM, Barefoot JC, Grichnik K, Helms MJ, et al. Central nervous system serotonin function and cardiovascular responses to stress. Psychosom Med. 2001;63(2):300-5. https://doi.org/10.1097/00006842-200103000-00016 PMid:11292279

Lavi E, Cong L. Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection. Exp Mol Pathol. 2020;115:104474. https://doi.org/10.1016/j.yexmp.2020.104474 PMid:32454103

Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci 2018;21(10):1380-91. https://doi.org/10.1038/s41593-018-0227-9 PMid:30224810

Negi N, Das BK. CNS: Not an immunoprivilaged site anymore but a virtual secondary lymphoid organ. Int Rev Immunol. 2018;37(1):57-68. https://doi.org/10.1080/08830185.2017.1357719 PMid:28961037

Yanev P, Poinsatte K, Hominick D, Khurana N, Zuurbier KR, Berndt M, et al. Impaired meningeal lymphatic vessel development worsens stroke outcome. J Cereb Blood Flow Metab. 2020;40(2):263-75. https://doi.org/10.1177/0271678X18822921 PMid:30621519

Chen J, He J, Ni R, Yang Q, Zhang Y, Luo L. Cerebrovascular injuries induce lymphatic invasion into brain parenchyma to guide vascular regeneration in zebrafish. Dev Cell. 2019;49(5):697-710.e5. https://doi.org/10.1016/j.devcel.2019.03.022 PMid:31006646

Benakis C, Llovera G, Liesz A. The meningeal and choroidal infiltration routes for leukocytes in stroke. Ther Adv Neurol Disord. 2018;11:1756286418783708. https://doi.org/10.1177/1756286418783708 PMid:29977343

Rua R, McGavern DB. Advances in meningeal immunity. Trends Mol Med. 2018;24(6):542-59. https://doi.org/10.1016/j.molmed.2018.04.003 PMid:29731353

Mander BA, Winer JR, Walker MP. Sleep and human aging. Neuron. 2017;94(1):19-36. https://doi.org/10.1016/j.neuron.2017.02.004 PMid:28384471

Hablitz LM, Vinitsky HS, Sun Q, Stæger FF, Sigurdsson B, Mortensen KN, et al. Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. Sci Adv. 2019;5(2):eaav5447. https://doi.org/10.1126/sciadv.aav5447 PMid:30820460

Tay TL, Savage JC, Hui CW, Bisht K, Tremblay M. Microglia across the lifespan: From origin to function in brain development, plasticity and cognition. J Physiol. 2017;595(6):1929-45. https:// doi.org/10.1113/jp272134

Clarke LE, Liddelow SA, Chakraborty C, Münch AE, Heiman M, Barres BA. Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci U S A. 2018;115:E1896-905. https://doi.org/10.1073/pnas.1800165115 PMid:29437957

Cotrina ML, Nedergaard M. Astrocytes in the aging brain. J Neurosci Res. 2002;67(1):1-10. https://doi.org/10.1002/jnr.10121 PMid:11754075

Finch CE. Neurons, glia, and plasticity in normal brain aging. Neurobiol Aging. 2003;24(Suppl 1):S123-7. https://doi.org/10.1016/s0197-4580(03)00051-4 PMid:12829120

Campuzano O, Castillo-Ruiz MM, Acarin L, Castellano B, Gonzalez B. Increased levels of proinflammatory cytokines in the aged rat brain attenuate injury-induced cytokine response after excitotoxic damage. J Neurosci Res. 2009;87(11):2484-97. https://doi.org/10.1002/jnr.22074 PMid:19326443

Thrane VR, Thrane AS, Plog BA, Thiyagarajan M, Iliff JJ, Deane R, et al. Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain. Sci Rep. 2013;3:2582. https://doi.org/10.1038/srep02582 PMid:24002448

Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiatry. 2010;67(6):505-12. https://doi.org/10.1016/j.biopsych.2009.02.013 PMid:19358976

Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O, et al. Multifactorial intervention and cardiovascular disease in patients with Type 2 diabetes. N Engl J Med. 2003;348(5):383-93. https://doi.org/10.1056/NEJMoa021778

Seravalle G, Grassi G. Obesity and hypertension. Pharmacol Res. 2017;122:1-7. https://doi.org/10.1016/j.phrs.2017.05.013 PMid:28532816

Wysocki M, Luo X, Schmeidler J, Dahlman K, Lesser GT, Grossman H, et al. Hypertension is associated with cognitive decline in elderly people at high risk for dementia. Am J Geriatr Psychiatry. 2012;20(2):179-87. https://doi.org/10.1097/JGP.0b013e31820ee833 PMid:21814158

Kummer BR, Diaz I, Wu X, Aaroe AE, Chen ML, Iadecola C, et al. Associations between cerebrovascular risk factors and Parkinson disease. Ann Neurol. 2019;86(4):572-81. https://doi.org/10.1002/ana.25564 PMid:31464350

de Heus RA, Rikkert MG, Tully PJ, Lawlor BA, Claassen JA, NILVAD Study Group. Blood pressure variability and progression of clinical Alzheimer disease. Hypertension. 2019;74(5):1172-80. https://doi.org/10.1161/HYPERTENSIONAHA.119.13664 PMid:31542965

Mortensen KN, Sanggaard S, Mestre H, Lee H, Kostrikov S, Xavier AL, et al. Impaired glymphatic transport in spontaneously hypertensive rats. J Neurosci. 2019;39(32):6365-77. https://doi.org/10.1523/JNEUROSCI.1974-18.2019 PMid:31209176

Blair GW, Thrippleton MJ, Shi Y, Hamilton I, Stringer M, Chappell F, et al. Intracranial hemodynamic relationships in patients with cerebral small vessel disease. Neurology. 2020;94(21):e2258-69. https://doi.org/10.1212/WNL.0000000000009483 PMid:32366534

Geurts LJ, Zwanenburg JJ, Klijn CJ, Luijten PR, Biessels GJ. Higher pulsatility in cerebral perforating arteries in patients with small vessel disease related stroke, a 7T MRI Study. Stroke. 2019;50:62-8.

Lorente-Cebrián S, Costa AG, Navas-Carretero S, Zabala M, Martínez JA, Moreno-Aliaga MJ. Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: A review of the evidence. J Physiol Biochem. 2013;69(3):633-51. https://doi.org/10.1007/s13105-013-0265-4 PMid:23794360

Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci.

;15(12):771-85. https://doi.org/10.1038/nrn3820 PMid:25387473

Ren H, Luo C, Feng Y, Yao X, Shi Z, Liang F, et al. Omega-3 polyunsaturated fatty acids promote amyloid-b clearance from the brain through mediating the function of the glymphatic system. FASEB J. 2017;31(1):282-93. https://doi.org/10.1096/fj.201600896 PMid:27789520

Zhang E, Wan X, Yang L, Wang D, Chen Z, Chen Y, et al. Omega-3 polyunsaturated fatty acids alleviate traumatic brain injury by regulating the glymphatic pathway in mice. Front Neurol. 2020;11:707. https://doi.org/10.3389/fneur.2020.00707 PMid:32765412

Chan JK, Trinder J, Colrain IM, Nicholas CL. The acute effects of alcohol on sleep electroencephalogram power spectra in late adolescence. Alcohol Clin Exp Res. 2015;39(2):291-9. https://doi.org/10.1111/acer.12621 PMid:25597245