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Physiology and Constituents of CSF

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Cerebrospinal Fluid in Clinical Neurology

Abstract

CSF protects the CNS in different ways involving metabolic homeostasis, supply of nutrients, functioning as lymphatic system, and regulation of intracranial pressure.

CSF is produced by the choroid plexus, brain interstitium, and the meninges, and it circulates in craniocaudal direction from ventricles to spinal subarachnoid space from where it is removed via craniocaudal lymphatic routes and venous system. The CSF is renewed 3–5 times daily, and its molecular constituents are mainly blood derived (80 %), while the remainder consists of brain-derived and intrathecally produced molecules (20 %).

The transfer of molecules between the blood–brain and blood–CSF barriers is selectively regulated by diffusion (e.g., passive or facilitated transport for proteins) or active transport (e.g., glucose). Aquaporin-4 channels, abundantly localized at the blood–brain interface, are involved in the regulation of extracellular space volume, potassium buffering, cerebrospinal fluid circulation, and interstitial fluid absorption.

The concentration of CSF constituents is influenced by multiple factors most significantly by blood concentration, protein size, blood–CSF barrier integrity, and intrathecal production.

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References

  • Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ et al (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37(1):13–25

    Google Scholar 

  • Battal B, Kocaoglu M, Bulakbasi N et al (2011) Cerebrospinal fluid flow imaging by using phase-contrast MR technique. Br J Radiol 84(1004):758–765

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Blödorn B, Bruck W, Tumani H et al (1999) Expression of the beta-trace protein in human pachymeninx as revealed by in situ hybridization and immunocytochemistry. J Neurosci Res 57(5):730–734

    Article  PubMed  Google Scholar 

  • Brettschneider J, Claus A, Kassubek J, Tumani H (2005) Isolated blood-cerebrospinal fluid barrier dysfunction: prevalence and associated diseases. J Neurol 252:1067–1073

    Article  CAS  PubMed  Google Scholar 

  • Brinker T, Stopa E, Morrison J, Klinge P (2014) A new look at cerebrospinal fluid circulation fluids and barriers of the CNS. http://www.fluidsbarrierscns.com/content/11/1/10

  • Bulat M, Klarica M (2011) Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev 2011(65):99–112

    Article  Google Scholar 

  • Buvanendran A, Kroin JS, Della Valle CJ, Moric M, Tuman KJ (2012) Cerebrospinal fluid neurotransmitter changes during the perioperative period in patients undergoing total knee replacement: a randomized trial. Anesth Analg 114(2):434–441

    Article  CAS  PubMed  Google Scholar 

  • Carrion E, Hertzog JH, Medlock MD, Hauser GJ, Dalton HJ (2001) Use of acetazolamide to decrease cerebrospinal fluid production in chronically ventilated patients with ventriculopleural shunts. Arch Dis Child 84(1):68–71

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cserr HF, Harling-Berg CJ, Knopf PM (1992) Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol 2(4):269–276

    Article  CAS  PubMed  Google Scholar 

  • Davson H, Hollingsworth G, Segal MB (1970) The mechanism of drainage of the cerebrospinal fluid. Brain 93(4):665–678

    Article  CAS  PubMed  Google Scholar 

  • Deisenhammer F, Egg R, Giovannoni G, Hemmer B, Petzold A, Sellebjerg F, Teunissen C, Tumani H (2009) EFNS guidelines on disease-specific CSF investigations. Eur J Neurol 16(6):760–770

    Article  CAS  PubMed  Google Scholar 

  • Felgenhauer K (1974) Protein size and cerebrospinal fluid composition. Klin Wochenschr 52:1158–1164

    Article  CAS  PubMed  Google Scholar 

  • Felgenhauer K (1995) The filtration concept of the blood-CSF barrier as basis for the differentiation of CSF proteins. In: Greenwood J, Begley DJ, Segal MB (eds) New concepts of a blood-brain barrier. Plenum Press, New York, pp 209–217

    Chapter  Google Scholar 

  • Felgenhauer K, Schliep G, Rapic N (1976) Evaluation of the blood-CSF barrier by protein gradients and the humoral immune response within the central nervous system. J Neurol Sci 30:113–128

    Article  CAS  PubMed  Google Scholar 

  • Gerber J, Tumani H, Kolenda H, Nau R (1998) Lumbar and ventricular CSF protein, leukocytes, and lactate in suspected bacterial CNS infections. Neurology 51:1710–1714

    Article  CAS  PubMed  Google Scholar 

  • Greitz D, Hannerz J (1996) A proposed model of cerebrospinal fluid circulation: observations with radionuclide cisternography. AJNR Am J Neuroradiol 17(3):431–438

    CAS  PubMed  Google Scholar 

  • Hayaishi O (2000) Molecular mechanisms of sleep-wake regulation: a role of prostaglandin D2. Philos Trans R Soc Lond B Biol Sci 355(1394):275–280

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Honkanen RA, McBath H, Kushmerick C, Callender GE, Scarlata SF, Fenstermacher JD, Haspel HC (1995) Barbiturates inhibit hexose transport in cultured mammalian cells and human erythrocytes and interact directly with purified GLUT-1. Biochemistry 34(2):535–544

    Article  CAS  PubMed  Google Scholar 

  • Iliff JJ, Wang M, Liao Y et al (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 4:147

    Article  Google Scholar 

  • Jones CF, Lee JH, Kwon BK, Cripton PA (2012) Development of a large-animal model to measure dynamic cerebrospinal fluid pressure during spinal cord injury: laboratory investigation. J Neurosurg Spine 16(6):624–635

    Article  PubMed  Google Scholar 

  • Jordan W, Tumani H, Cohrs S et al (2004) Prostaglandin D synthase (beta-trace) in healthy human sleep. Sleep 27(5):867–874

    PubMed  Google Scholar 

  • Keep RF, Ulanski LJ 2nd, Xiang J, Ennis SR, Lorris Betz A (1999) Blood-brain barrier mechanisms involved in brain calcium and potassium homeostasis. Brain Res 815(2):200–205

    Article  CAS  PubMed  Google Scholar 

  • Link H, Tibbling G (1977) Principles of albumin and IgG analyses in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis. Scand J Clin Lab Invest 37:397–401

    Article  CAS  PubMed  Google Scholar 

  • McComb JG (1983) Recent research into the nature of cerebrospinal fluid formation and absorption. J Neurosurg 1983(59):369–383

    Article  Google Scholar 

  • Nagelhus EA, Ottersen OP (2013) Physiological roles of aquaporin-4 in brain. Physiol Rev 93:1543–1562

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nakada T (2014) Cerebrospinal fluid physiology and movement. Croat Med J 55:328–336

    Article  PubMed Central  PubMed  Google Scholar 

  • Nau R, Sörgel F, Prange HW (1994) Lipophilicity at pH 7.4 and molecular size govern the entry of the free serum fraction of drugs into the cerebrospinal fluid in humans with uninflamed meninges. J Neurol Sci 122(1):61–65

    Article  CAS  PubMed  Google Scholar 

  • Nilsson C, Stahlberg F, Thomsen C, Henriksen O, Herning M, Owman C (1992) Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging. Am J Physiol 262:20–24

    Google Scholar 

  • Oldendorf WH, Hyman S, Braun L, Oldendorf SZ (1972) Blood-brain barrier: penetration of morphine, codeine, heroin, and methadone after carotid injection. Science 178(4064):984–986

    Article  CAS  PubMed  Google Scholar 

  • Oreskovic D, Klarica M (2010) The formation of cerebrospinal fluid: nearly a hundred years of interpretations and misinterpretations. Brain Res Rev 64:241–262

    Article  CAS  PubMed  Google Scholar 

  • Quincke HI (1891) Die Lumbalpunktion des Hydrocephalus [German]. Berl Klin Wochschr 32:861–862

    Google Scholar 

  • Reiber H (1994) Flow rate of cerebrospinal fluid (CSF)–a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 122:189–203

    Article  CAS  PubMed  Google Scholar 

  • Reiber H (2001) Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta 310(2):173–186

    Article  CAS  PubMed  Google Scholar 

  • Reiber H, Felgenhauer K (1987) Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta 163:319–328

    Article  CAS  PubMed  Google Scholar 

  • Steensberg A, Dalsgaard MK, Secher NH, Pedersen BK (2006) Cerebrospinal fluid IL-6, HSP72, and TNF-alpha in exercising humans. Brain Behav Immun 20(6):585–589

    Article  CAS  PubMed  Google Scholar 

  • Stewart RM (1922) Critical review: the cerebrospinal fluid: its source, distribution, and circulation. J Neurol Psychopathol 3(10):144–166

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sussmuth SD, Reiber H, Tumani H (2001) Tau protein in cerebrospinal fluid (CSF): a blood-CSF barrier related evaluation in patients with various neurological diseases. Neurosci Lett 300(2):95–98

    Article  CAS  PubMed  Google Scholar 

  • Thompson EJ, Zeman A (1992) Fluids of the brain and the pathogenesis of MS. Neurochem Res 17(9):901–905

    Article  CAS  PubMed  Google Scholar 

  • Torbey MT, Geocadin RG, Razumovsky AY, Rigamonti D, Williams MA (2004) Utility of CSF pressure monitoring to identify idiopathic intracranial hypertension without papilledema in patients with chronic daily headache. Cephalalgia 24(6):495–502

    Article  CAS  PubMed  Google Scholar 

  • Tourtellotte WW, Potvin AR, Baumhefner RW et al (1980) Multiple sclerosis de novo CNS IgG synthesis. Effect of CNS irradiation. Arch Neurol 37:620–624

    Article  CAS  PubMed  Google Scholar 

  • Tumani H, Brettschneider J (2005) Brain specific proteins in CSF: factors influencing their concentration in CSF and clinical relevance. J Lab Med 29:421–428

    CAS  Google Scholar 

  • Tumani H, Nau R, Felgenhauer K (1998) Beta-trace protein in cerebrospinal fluid: a blood-CSF barrier-related evaluation in neurological diseases. Ann Neurol 44(6):882–889

    Article  CAS  PubMed  Google Scholar 

  • Tumani H, Shen G, Peter JB, Bruck W (1999) Glutamine synthetase in cerebrospinal fluid, serum, and brain: a diagnostic marker for Alzheimer disease? Arch Neurol 56(10):1241–1246

    Article  CAS  PubMed  Google Scholar 

  • Urayama K (1994) Origin of lumbar cerebrospinal fluid pulse wave. Spine 19(4):441–445

    Article  CAS  PubMed  Google Scholar 

  • Weisner B, Bernhardt W (1978) Protein fractions of lumbar, cisternal, and ventricular cerebrospinal fluid. Separate areas of reference. J Neurol Sci 37(3):205–214

    Article  CAS  PubMed  Google Scholar 

  • Widl K, Brettschneider J, Schattauer D, Süssmuth S, Huber R, Ludolph AC, Tumani H (2007) Erythropoietin in cerebrospinal fluid: age-related reference values and relevance in neurological disease. Neurochem Res 32(7):1163–1168

    Article  CAS  PubMed  Google Scholar 

  • Wynter WE (1891) Four cases of tubercular meningitis in which paracentesis was performed for the relief of fluid pressure. Lancet 137:981–982

    Article  Google Scholar 

  • Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M (2013) Sleep drives metabolite clearance from the adult brain. Science 342(6156):373–377

    Article  CAS  PubMed  Google Scholar 

  • Yadav YR, Parihar V, Sinha M (2010) Lumbar peritoneal shunt. Neurol India 58(2):179–184

    Article  PubMed  Google Scholar 

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Correspondence to Hayrettin Tumani .

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Tumani, H. (2015). Physiology and Constituents of CSF. In: Deisenhammer, F., Sellebjerg, F., Teunissen, C., Tumani, H. (eds) Cerebrospinal Fluid in Clinical Neurology. Springer, Cham. https://doi.org/10.1007/978-3-319-01225-4_3

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  • DOI: https://doi.org/10.1007/978-3-319-01225-4_3

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