Abstract
In this article, we suggest that the glymphatic system of the brain can play an important role in the pathogenesis of high-altitude cerebral edema (HACE). Water enters the intercellular space of the brain primarily through aquaporin-4 (AQP-4) water channels, the main component of the glymphatic system, whereas acetazolamide, pharmacological agent used in the prevention of HACE, is the blocker of the AQP-4 molecule. In animal experiments, cerebral edema caused by hypobaric hypoxia was associated with an increased expression of AQP-4 by astrocytes. Also, the glymphatic system is primarily active during sleep, although sleep at high altitude is a well-known risk factor of developing HACE. All these findings support our hypothesis. We suggest that future research on the prevention and treatment of HACE should involve factors that are already known to modify activity of the glymphatic system, such as angiotensin-converting enzyme inhibitors or other pharmaceutical agents affecting noradrenergic system of the brain, body posture during sleep, anatomy of the veins draining the cranial cavity, and the influence of physical activity before and during exposure to high altitude, especially in relation to sleep.
References
Jun 23, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marios C PapadopoulosA S Verkman
Jul 22, 2004·High Altitude Medicine & Biology·Peter H Hackett, Robert C Roach
Dec 9, 2008·Journal of Neurology, Neurosurgery, and Psychiatry·P ZamboniF Salvi
Nov 26, 2010·Phlebology·P Zamboni, R Galeotti
Apr 15, 2011·Neurology·R ZivadinovB Weinstock-Guttman
Jun 26, 2012·High Altitude Medicine & Biology·Bengt KayserMartin R Tramèr
Oct 19, 2013·Science·Lulu XieMaiken Nedergaard
Oct 23, 2013·Sub-cellular Biochemistry·Erik R Swenson
Dec 19, 2013·BMC Medicine·Robert Zivadinov, Chih-Ping Chung
Sep 23, 2014·Trends in Neurosciences·Alexander S ThraneMaiken Nedergaard
May 8, 2015·Neurochemical Research·Nadia Aalling JessenMaiken Nedergaard
Aug 8, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hedok LeeHelene Benveniste
Aug 22, 2015·Journal of Applied Physiology·Mark H Wilson, Christopher H E Imray
Aug 22, 2015·Journal of Applied Physiology·Erik R Swenson
Oct 17, 2015·Journal of Applied Physiology·Kang WangDavid J Dubowitz
Oct 24, 2015·Journal of Applied Physiology·Justin S LawleyRobert C Roach
Jan 10, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ravjit S SagooUNKNOWN Birmingham Medical Research and Expedition Society
Feb 26, 2016·Microscopy·Akiko KamegawaYoshinori Fujiyoshi
Sep 27, 2016·CNS & Neurological Disorders Drug Targets·José V LafuenteSusana Bulnes
Oct 1, 2016·International Journal of Molecular Sciences·Guanghui Tang, Guo-Yuan Yang
Apr 17, 2017·Emergency Medicine Clinics of North America·Christopher Davis, Peter Hackett
Apr 24, 2017·Brain, Behavior, and Immunity·Yanzhao ZhouLingling Zhu
Oct 22, 2017·Life Sciences·Chi WangChengbin Wang
Oct 29, 2017·Neuroscience Letters·Stephanie von Holstein-RathlouMaiken Nedergaard
Dec 2, 2017·Annual Review of Pathology·Benjamin A Plog, Maiken Nedergaard
Feb 13, 2018·Molecular Immunology·Gu GongXiaowu Wang
May 4, 2018·Neural Regeneration Research·Zhong-Lei SunXu-Yi Chen