Hydrocephalus Revisited: New Insights into Dynamics of Neurofluids on Macro- and Microscales

Abstract

New experimental and clinical findings question the historic view of hydrocephalus and its 100-year-old classification. In particular, real-time magnetic resonance imaging (MRI) evaluation of cerebrospinal fluid (CSF) flow and detailed insights into brain water regulation on the molecular scale indicate the existence of at least three main mechanisms that determine the dynamics of neurofluids: (1) inspiration is a major driving force; (2) adequate filling of brain ventricles by balanced CSF upsurge is sensed by cilia; and (3) the perivascular glial network connects the ependymal surface to the pericapillary Virchow–Robin spaces. Hitherto, these aspects have not been considered a common physiologic framework, improving knowledge and therapy for severe disorders of normal-pressure and posthemorrhagic hydrocephalus, spontaneous intracranial hypotension, and spaceflight disease.

Keywords

cerebrospinal fluid - real-time MRI - hydrocephalus - space flight disease - aquaporin - spontaneous intracranial hypotension - neural tube defect

Author Contributions

H. C. L., S. D.-K., and J. F. edited the manuscript; H. C. L., S. D.-K., H. C. B., and J. G. defined the scope, objective, and clinical details. H. C. L., S. D.-K., H. C. B., J. F., J.-G., and S. S. reviewed the manuscript.

Competing Interests

The authors declare no competing financial interests.

Publikationsverlauf

Eingereicht: 02. September 2020

Angenommen: 07. März 2021

Artikel online veröffentlicht:
30. Juni 2021

• References

• 1 Isaacs AM, Riva-Cambrin J, Yavin D. et al. Age-specific global epidemiology of hydrocephalus: systematic review, metanalysis and global birth surveillance. PLoS One 2018; 13 (10) e0204926
• 2 Dewan MC, Rattani A, Mekary R. et al. Global hydrocephalus epidemiology and incidence: systematic review and meta-analysis. J Neurosurg 2018; 37 (02) 1-15
• 3 Jaraj D, Wikkelsø C, Rabiei K. et al. Mortality and risk of dementia in normal-pressure hydrocephalus: a population study. Alzheimers Dement 2017; 13 (08) 850-857
• 4 Dandy WE. Experimental hydrocephalus. Ann Surg 1919; 70 (02) 129-142
• 5 Greitz D, Wirestam R, Franck A, Nordell B, Thomsen C, Ståhlberg F. Pulsatile brain movement and associated hydrodynamics studied by magnetic resonance phase imaging. The Monro-Kellie doctrine revisited. Neuroradiology 1992; 34 (05) 370-380
• 6 Greitz D. The hydrodynamic hypothesis versus the bulk flow hypothesis. Neurosurg Rev 2004; 27 (04) 299-300
• 7 Klarica M, Oresković D, Bozić B, Vukić M, Butković V, Bulat M. New experimental model of acute aqueductal blockage in cats: effects on cerebrospinal fluid pressure and the size of brain ventricles. Neuroscience 2009; 158 (04) 1397-1405
• 8 Klarica M, Miše B, Vladić A, Radoš M, Orešković D. “Compensated hyperosmolarity” of cerebrospinal fluid and the development of hydrocephalus. Neuroscience 2013; 248: 278-289
• 9 Orešković D, Klarica M. A new look at cerebrospinal fluid movement. Fluids Barriers CNS 2014; 11 (01)
• 10 Brinker T, Stopa E, Morrison J, Klinge P. A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 2014; 11 (01) 10-16
• 11 Buishas J, Gould IG, Linninger AA. A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces. Croat Med J 2014; 55 (05) 481-497
• 12 Jones HC, Keep RF, Drewes LR. CNS fluid and solute movement: physiology, modelling and imaging. Fluids Barriers CNS 2020; 17: 12
• 13 Frahm J, Voit D, Uecker M. Real-time magnetic resonance imaging: radial gradient-echo sequences with nonlinear inverse reconstruction. Invest Radiol 2019; 54 (12) 757-766
• 14 Dreha-Kulaczewski S, Konopka M, Joseph AA. et al. Respiration and the watershed of spinal CSF flow in humans. Sci Rep 2018; 8 (01) 5594-5597
• 15 Papadopoulos MC, Verkman AS. Aquaporin water channels in the nervous system. Nat Rev Neurosci 2013; 14 (04) 265-277
• 16 Bock HC, Dreha-Kulaczewski SF, Alaid A, Gärtner J, Ludwig HC. Upward movement of cerebrospinal fluid in obstructive hydrocephalus-revision of an old concept. Childs Nerv Syst 2019; 35 (05) 833-841
• 17 Matsumae M, Kuroda K, Yatsushiro S. et al. Changing the currently held concept of cerebrospinal fluid dynamics based on shared findings of cerebrospinal fluid motion in the cranial cavity using various types of magnetic resonance imaging techniques. Neurol Med Chir (Tokyo) 2019; 59 (04) 133-146
• 18 Dreha-Kulaczewski S, Joseph AA, Merboldt KD, Ludwig HC, Gärtner J, Frahm J. Identification of the upward movement of human CSF in vivo and its relation to the brain venous system. J Neurosci 2017; 37 (09) 2395-2402
• 19 Yamada S, Miyazaki M, Kanazawa H. et al. Visualization of cerebrospinal fluid movement with spin labeling at MR imaging: preliminary results in normal and pathophysiologic conditions. Radiology 2008; 249 (02) 644-652
• 20 Henriques CQ. The veins of the vertebral column and their role in the spread of cancer. Ann R Coll Surg Engl 1962; 31 (01) 1-22
• 21 Groen RJM, Grobbelaar M, Muller CJF. et al. Morphology of the human internal vertebral venous plexus: a cadaver study after latex injection in the 21-25-week fetus. Clin Anat 2005; 18 (06) 397-403
• 22 Nystrom EU, Blomberg SG, Buffington CW. Transmural pressure of epidural veins in the thoracic and lumbar spine of pigs. Anesthesiology 1998; 89 (02) 449-455
• 23 Todorov L, VadeBoncouer T. Etiology and use of the “hanging drop” technique: a review. Pain Res Treat 2014; 2014 (04) 1-10
• 24 Dreha-Kulaczewski S, Joseph AA, Merboldt K-D, Ludwig H-C, Gärtner J, Frahm J. Inspiration is the major regulator of human CSF flow. J Neurosci 2015; 35 (06) 2485-2491
• 25 Takizawa K, Matsumae M, Sunohara S, Yatsushiro S, Kuroda K. Characterization of cardiac- and respiratory-driven cerebrospinal fluid motion based on asynchronous phase-contrast magnetic resonance imaging in volunteers. Fluids Barriers CNS 2017; 14 (01) 25
• 26 Yatsushiro S, Sunohara S, Atsumi H, Matsumae M, Kuroda K. Visualization and characterization of cerebrospinal fluid motion based on magnetic resonance imaging. In: Gürer B. ed. Hydrocephalus - Water on the Brain. InTech; 2018: 1-18
• 27 Yildiz S, Thyagaraj S, Jin N. et al. Quantifying the influence of respiration and cardiac pulsations on cerebrospinal fluid dynamics using real-time phase-contrast MRI. J Magn Reson Imaging 2017; 46 (02) 431-439
• 28 Fultz NE, Bonmassar G, Setsompop K. et al. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science 2019; 366 (6465): 628-631
• 29 von Mecklenburg C, Håkansson CH, Lindgren M. Effects of irradiation on the cilia of the Sylvian aqueduct. A scanning electron microscopic investigation. Acta Radiol Ther Phys Biol 1974; 13 (03) 232-240
• 30 Qi S-T, Fan J, Zhang X-A, Pan J. Reinvestigation of the ambient cistern and its related arachnoid membranes: an anatomical study. J Neurosurg 2011; 115 (01) 171-178
• 31 Park J-H, Park YS, Suk J-S. et al. Cerebrospinal fluid pathways from cisterns to ventricles in N-butyl cyanoacrylate-induced hydrocephalic rats. J Neurosurg Pediatr 2011; 8 (06) 640-646
• 32 Hussein S, Woischneck D, Niemeyer U. Microsurgical anatomy of the cisterna quadrigemina and cisterna velum interpositum. In: Bauer BL, Brock M, Klinger M. eds. Cerebellar Infarct. Midline Tumors. Minimally Invasive Endoscopic Neurosurgery (MIEN). Advances in Neurosurgery. Vol. 22. Berlin, Heidelberg, New York: Springer; 1994: 297-302
• 33 Boulton M, Flessner M, Armstrong D, Hay J, Johnston M. Determination of volumetric cerebrospinal fluid absorption into extracranial lymphatics in sheep. Am J Physiol 1998; 274 (01) R88-R96
• 34 Oi S, Di Rocco C. Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain. Childs Nerv Syst 2006; 22 (07) 662-669
• 35 Castaneyra-Ruiz L, Morales DM, McAllister JP. et al. Blood exposure causes ventricular zone disruption and glial activation in vitro. J Neuropathol Exp Neurol 2018; 77 (09) 803-813
• 36 Ihrie RA, Alvarez-Buylla A. Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. Neuron 2011; 70 (04) 674-686
• 37 Oliver C, González CA, Alvial G, Flores CA, Rodríguez EM, Bátiz LF. Disruption of CDH2/N-cadherin-based adherens junctions leads to apoptosis of ependymal cells and denudation of brain ventricular walls. J Neuropathol Exp Neurol 2013; 72 (09) 846-860
• 38 Kusne Y, Duran-Moreno M, Cabrales E. et al. Bi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories. Nat Commun 2017; 8: 13759
• 39 Faubel R, Westendorf C, Bodenschatz E, Eichele G. Cilia-based flow network in the brain ventricles. Science 2016; 353 (6295): 176-178
• 40 Di Rocco C, Pettorossi VE, Caldarelli M, Mancinelli R, Velardi F. Communicating hydrocephalus induced by mechanically increased amplitude of the intraventricular cerebrospinal fluid pressure: experimental studies. Exp Neurol 1978; 59 (01) 40-52
• 41 Foerster P, Daclin M, Asm S. et al. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Development 2017; 144 (02) 201-210
• 42 Swiderski RE, Agassandian K, Ross JL, Bugge K, Cassell MD, Yeaman C. Structural defects in cilia of the choroid plexus, subfornical organ and ventricular ependyma are associated with ventriculomegaly. Fluids Barriers CNS 2012; 9 (01) 22-35
• 43 Gato A, Desmond ME. Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis. Dev Biol 2009; 327 (02) 263-272
• 44 Korzh V. Development of brain ventricular system. Cell Mol Life Sci 2018; 75 (03) 375-383
• 45 Gato A, Alonso MI, Martín C. et al. Embryonic cerebrospinal fluid in brain development: neural progenitor control. Croat Med J 2014; 55 (04) 299-305
• 46 Guadagno E, Moukhles H. Laminin-induced aggregation of the inwardly rectifying potassium channel, Kir4.1, and the water-permeable channel, AQP4, via a dystroglycan-containing complex in astrocytes. Glia 2004; 47 (02) 138-149
• 47 Tham DKL, Joshi B, Moukhles H. Aquaporin-4 cell-surface expression and turnover are regulated by dystroglycan, dynamin, and the extracellular matrix in astrocytes. PLoS One 2016; 11 (10) e0165439
• 48 Nakada T, Kwee IL. Fluid dynamics inside the brain barrier: current concept of interstitial flow, glymphatic flow, and cerebrospinal fluid circulation in the brain. Neuroscientist 2019; 25 (02) 155-166
• 49 Nakada T, Kwee I, Igarashi H, Suzuki Y. Aquaporin-4 functionality and Virchow-Robin space water dynamics: physiological model for neurovascular coupling and glymphatic flow. Int J Mol Sci 2017; 18 (08) 1798
• 50 Gram M, Sveinsdottir S, Cinthio M. et al. Extracellular hemoglobin - mediator of inflammation and cell death in the choroid plexus following preterm intraventricular hemorrhage. J Neuroinflammation 2014; 11 (01) 200
• 51 McAllister JP, Guerra MM, Ruiz LC. et al. Ventricular zone disruption in human neonates with intraventricular hemorrhage. J Neuropathol Exp Neurol 2017; 76 (05) 358-375
• 52 Hasan-Olive MM, Enger R, Hansson H-A, Nagelhus EA, Eide PK. Pathological mitochondria in neurons and perivascular astrocytic endfeet of idiopathic normal pressure hydrocephalus patients. Fluids Barriers CNS 2019; 16 (01) 39-55
• 53 Verkman AS, Tradtrantip L, Smith AJ, Yao X. Aquaporin water channels and hydrocephalus. Pediatr Neurosurg 2017; 52 (06) 409-416
• 54 Nakada T. Virchow-Robin space and aquaporin-4: new insights on an old friend. Croat Med J 2014; 55: 328-336
• 55 Adzick NS, Thom EA, Spong CY. et al; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011; 364 (11) 993-1004
• 56 McLone DG, Knepper PA. The cause of Chiari II malformation: a unified theory. Pediatr Neurosci 1989; 15 (01) 1-12
• 57 Cosmi EV, Anceschi MM, Cosmi E, Piazze JJ, La Torre R. Ultrasonographic patterns of fetal breathing movements in normal pregnancy. Int J Gynaecol Obstet 2003; 80 (03) 285-290
• 58 Sival DA, Guerra M, den Dunnen WF. et al. Neuroependymal denudation is in progress in full-term human foetal spina bifida aperta. Brain Pathol 2011; 21 (02) 163-179
• 59 de Wit OA, den Dunnen WF, Sollie KM. et al. Pathogenesis of cerebral malformations in human fetuses with meningomyelocele. Cerebrospinal Fluid Res 2008; 5 (01) 4-13
• 60 Beck J, Gralla J, Fung C. et al. Spinal cerebrospinal fluid leak as the cause of chronic subdural hematomas in nongeriatric patients. J Neurosurg 2014; 121 (06) 1380-1387
• 61 Beck J, Raabe A, Schievink WI. et al. Posterior approach and spinal cord release for 360° repair of dural defects in spontaneous intracranial hypotension. Neurosurgery 2019; 84 (06) E345-E351
• 62 Wu C, Guan D, Ren M. et al. Aminophylline for treatment of postdural puncture headache: a randomized clinical trial. Neurology 2018; 90 (17) e1523-e1529
• 63 Van Ombergen A, Jillings S, Jeurissen B. et al. Brain ventricular volume changes induced by long-duration spaceflight. Proc Natl Acad Sci U S A 2019; 116 (21) 10531-10536
• 64 Van Ombergen A, Jillings S, Jeurissen B. et al. Brain tissue-volume changes in cosmonauts. N Engl J Med 2018; 379 (17) 1678-1680
• 65 Ludwig H-C, Frahm J, Gärtner J, Dreha-Kulaczewski S. Breathing drives CSF: Impact on spaceflight disease and hydrocephalus. Proc Natl Acad Sci U S A 2019; 116 (41) 20263-20264
• 66 Eide PK, Hansson H-A. Astrogliosis and impaired aquaporin-4 and dystrophin systems in idiopathic normal pressure hydrocephalus. Neuropathol Appl Neurobiol 2018; 44 (05) 474-490
• 67 Hasan-Olive MM, Hansson H-A, Enger R, Nagelhus EA, Eide PK. Blood-brain barrier dysfunction in idiopathic intracranial hypertension. J Neuropathol Exp Neurol 2019; 78 (09) 808-818
• 68 Castañeyra-Ruiz L, Hernández-Abad LG, Carmona-Calero EM, Castañeyra-Perdomo A, González-Marrero I. AQP1 overexpression in the CSF of obstructive hydrocephalus and inversion of its polarity in the choroid plexus of a Chiari malformation type ii case. J Neuropathol Exp Neurol 2019; 78 (07) 641-647
• 69 Gabrion J, Maurel D, Clavel B. et al. Changes in apical organization of choroidal cells in rats adapted to spaceflight or head-down tilt. Brain Res 1996; 734 (1–2): 301-315
• 70 Masseguin C, Corcoran M, Carcenac C. et al. Altered gravity downregulates aquaporin-1 protein expression in choroid plexus. J Appl Physiol (1985) 2000; 88 (03) 843-850
• 71 Trillo-Contreras JL, Ramírez-Lorca R, Hiraldo-González L. et al. Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus. Biochim Biophys Acta Mol Basis Dis 2018; 1864 (10) 3515-3526
• 72 Wang Y, Tajkhorshid E. Nitric oxide conduction by the brain aquaporin AQP4. Proteins 2010; 78 (03) 661-670
• 73 Chachlaki K, Prevot V. Nitric oxide signalling in the brain and its control of bodily functions. Br J Pharmacol 2020; 177 (24) 5437-5458
• 74 Barbaresi P, Fabri M, Mensà E. Characterization of NO-producing neurons in the rat corpus callosum. Brain Behav 2014; 4 (03) 317-336
• 75 Li D, Shirakami G, Zhan X, Johns RA. Regulation of ciliary beat frequency by the nitric oxide-cyclic guanosine monophosphate signaling pathway in rat airway epithelial cells. Am J Respir Cell Mol Biol 2000; 23 (02) 175-181
• 76 Eisenhut M, Choudhury S. In premature newborns intraventricular hemorrhage causes cerebral vasospasm and associated neurodisability via heme-induced inflammasome-mediated interleukin-1 production and nitric oxide depletion. Front Neur 2017; 8: 423
• 77 Campos-Ordoñez T, Herranz-Pérez V, Chaichana KL. et al. Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone. Exp Neurol 2014; 261: 236-244
• 78 Vaziri ND, Ding Y, Sangha DS, Purdy RE. Upregulation of NOS by simulated microgravity, potential cause of orthostatic intolerance. J Appl Physiol (1985) 2000; 89 (01) 338-344
• 79 Kawada T. Obstructive sleep apnea in patients with idiopathic normal-pressure hydrocephalus. J Neurol Sci 2019; 397: 155
• 80 Román GC, Jackson RE, Fung SH, Zhang YJ, Verma AK. Sleep-disordered breathing and idiopathic normal-pressure hydrocephalus: recent pathophysiological advances. Curr Neurol Neurosci Rep 2019; 19 (07) 39-48
• 81 Hasan-Olive MM, Enger R, Hansson H-A, Nagelhus EA, Eide PK. Loss of perivascular aquaporin-4 in idiopathic normal pressure hydrocephalus. Glia 2019; 67 (01) 91-100
• 82 Long X, Foussier J, Fonseca P, Haakma R, Aarts RM. Respiration amplitude analysis for REM and NREM sleep classification. Annu Int Conf IEEE Eng Med Biol Soc 2013; 2013: 5017-5020
• 83 Rainey-Smith SR, Mazzucchelli GN, Villemagne VL. et al; AIBL Research Group. Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden. Transl Psychiatry 2018; 8 (01) 47
• 84 Benveniste H, Lee H, Volkow ND. The glymphatic pathway: waste removal from the CNS via cerebrospinal fluid transport. Neuroscientist 2017; 23 (05) 454-465
• 85 Marshall-Goebel K, Mulder E, Bershad E. et al. Intracranial and intraocular pressure during various degrees of head-down tilt. Aerosp Med Hum Perform 2017; 88 (01) 10-16
• 86 Kramer LA, Hasan KM, Sargsyan AE. et al; SPACECOT Investigators Group. Quantitative MRI volumetry, diffusivity, cerebrovascular flow, and cranial hydrodynamics during head-down tilt and hypercapnia: the SPACECOT study. J Appl Physiol (1985) 2017; 122 (05) 1155-1166
• 87 Cromwell RL, Scott JM, Downs M, Yarbough PO, Zanello SB, Ploutz-Snyder L. Overview of the NASA 70-day Bed Rest Study. Med Sci Sports Exerc 2018; 50 (09) 1909-1919
• 88 Gabrion J, Herbuté S, Oliver J. et al. Choroidal responses in microgravity. (SLS-1, SLS-2 and hindlimb-suspension experiments). Acta Astronaut 1995; 36 (8–12): 439-448