Neurological Surgery 脳神経外科42巻12号

2014年12月発行

総説

髄液の産生と吸収の再考

著者： 宮嶋雅一¹ 新井一¹

所属機関： ¹順天堂大学脳神経外科

ページ範囲：P.1095 - P.1106

Ⅰ．はじめに
　従来，髄液の大部分は脈絡叢から産生され，中脳水道を通り，Luschka孔とMagendie孔より出て，脳底槽に達する．そして頭頂部に向かって循環し，脳表くも膜下腔に至り，いわゆるくも膜顆粒（絨毛）から上矢状洞に吸収され，体循環に戻るとされてきた．また，一部の髄液は脊髄くも膜下腔を循環するとされてきた（Fig.1）．この髄液循環の仮説は，多数の偉大な先人の優れた業績によるものである．しかし100年を経た現在，最近の研究結果および臨床的観察から，過去の研究方法の不備と研究結果の誤った解釈が明らかになり，この髄液循環の仮説を再考する必要性が生じて来た．本稿では髄液生理学について歴史を踏まえて再考する．

参考文献

1) Agre P, Nielsen S, Ottersen OP：Towards a molecular understanding of water homeostasis in the brain. Neuroscience 129：849-850, 2004

2) Arnold W, Ritter R, Wagner WH：Quantitative studies on the drainage of the cerebrospinal fluid into the lymphatic system. Acta Otolaryngol 76：156-161, 1973

3) Bering EA Jr：Water exchange of central nervous system and cerebrospinal fluid. J Neurosurg 9：275-287, 1952

4) Bering EA Jr, Sato O：Hydrocephalus：Changes in formation and absorption of cerebrospinal fluid within the cerebral ventricles. J Neurosurg 20：1050-1063, 1963

5) Bowsher D：Pathways of absorption of from the cerebrospinal fluid：An autoradiographic study in the cat. Anat Rec 128：23-39, 1957

6) Bradbury MW：Proportion of cerebrospinal fluid draining into jugular lymphatic trunks of the cat. Proceedings of the Physiological Society, 1977, pp67-68

7) Bradbury MW, Cole DF：The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humour. J Physiol 299：353-365, 1980

8) Bradbury MW, Cserr HF, Westrop RJ：Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit. Am J Physiol 240：F329-F336, 1981

9) Brightman MW：The distribution within the brain of ferritin injected into cerebrospinal fluid compartment 1. Ependymal distribution. J Cell Biol 26：99-123, 1965

10) Brightman MW：The distribution within the brain of ferritin injected into cerebrospinal fluid compartment 2. Parenchymal distribution. Am J Anat 117：193-219, 1965

11) Brightman MW：The intracerebral movement of proteins injected into blood and cerebrospinal fluid of mice. Prog Brain Res 29：19-40, 1968

12) Brodbelt A, Stoodley M：CSF pathways：a review. Br J Neurosurg 21：510-520, 2007

13) Brown PD, Davies SL, Speake T, Millar ID：Molecular mechanisms of cerebrospinal fluid production. Neuroscience 129：957-970, 2004

14) Bulat M：Dynamics and statics of the cerebrospinal fluid：the classic and new hypothesis. In：Avezaat CJJ（Ed), Intracranial Pressure VIII. Springer-Verlag, Berlin, 1993, pp726-730

15) Bulat M, Lupret V, Oresković D, Klarica M：Transventricular and transpial absorption of cerebrospinal fluid into cerebral microvessels. Coll Antropol 32（Suppl 1）：43-50, 2008

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

17) Chen F, Deng XF, Liu B, Zou LN, Wang DB, Han H：Arachnoid granulations of middle cranial fossa：a population study between cadaveric dissection and in vivo computed tomography examination. Surg Radiol Anat 33：215-221, 2011

18) Crone C：The permeability of capillaries in various organs as determined by use of the indicator diffusion method. Acta Physiol Scand 58：292-305, 1963

19) Cserr HF, Ostrach LH：Bulk flow of interstitial fluid after intracranial injection of blue dextran 2000. Exp Neurol 45：50-60, 1974

20) Cserr HF：Bulk flow of cerebral extracellular fluid as a possible mechanism of CSF-Brain exchange. In：Fluid Environment of the Brain, Cserr HF, Fenstermacher JD, Fencl V（eds), Academic Press Inc, New York, 1975, pp215-224

21) Cserr HF, Cooper DN, Milhorat TH：Flow of cerebral interstitial fluid as indicated by the removal of extracellular markers from the rat caudate nucleus. Exp Eye Res 25 Suppl：461-473, 1977

22) Cserr HF：Convection of brain interstitial fluid and its drainage into deep cervical lymph. Abstract 097, The International Symposium on Intracranial Pressure, 1982, p228

23) Cushing H：Studies on the cerebrospinal fluid：I. Introduction. J Med Res 31：1-19, 1914

24) Davson H：Physiology of the Cerebrospinal Fluid. Churchill, London, 1967

25) Davson H, Welch K, Segal MB：Physiology and Pathophysiology of the Cerebrospinal Fluid. Churchill Livingstone, Edinburgh, 1987

26) Dandy WE, Blackfan KD：Internal hydrocephalus：experimental, clinical and pathological study. Am J Dis Child 8：406-482, 1914

27) Di Chiro G：Movement of the cerebrospinal fluid in human beings. Nature 204：290-291, 1964

28) Di Chiro G：Observations on the circulation of the cerebrospinal fluid. Acta Radiol Diagn（Stockh）5：988-1002, 1966

29) Drayer BP, Rosenbaum AE, Higman HB：Cerebrospinal fluid imaging using serial metrizamide CT cisternography. Neuroradiology 13：7-17, 1977

30) Edsbagge M, Tisell M, Jacobsson L, Wikkelso C：Spinal CSF absorption in healthy individuals. Am J Physiol Regul Integr Comp Physiol 287：R1450-R1455, 2004

31) Elman R：Spinal arachnoid granulations with especial reference to the cerebrospinal fluid. Johns Hopkins Hosp Bull 34：99-104, 1923

32) Erlich SS, McComb JG, Hyman S, Weiss MH：Ultrastructure of the orbital pathway for cerebrospinal fluid drainage in rabbits. J Neurosurg 70：926-931, 1989

33) Fenstermacher JD, Patlak CS：The exchange of material between cerebrospinal fluid and brain. In：Fluid Environment of the Brain, Cserr HF, Fenstermacher JD, Fencl V（eds), Academic Press Inc, New York, 1975, pp201-214

34) Fenstermacher JD, Kaye T：Drug “diffusion” within brain. Ann N Y Acad Sci 531：29-39, 1988

35) Field EJ, Brierley JB：The retro-orbital tissue as a site of outflow of cerebrospinal fluid. Proc Roy Soc Med 42：447-450, 1949

36) Flexner LB, Winters H：The rate of formation of cerebrospinal fluid in etherized cats. Am J Physiol 101：697-710, 1932

37) Flexner LB：The water of the cerebrospinal fluid. Variations of its rate of flow with variation of ventricular pressure. Am J Physiol 106：170-174, 1933

38) Foltz E, Blanks J, Morton ME：Experimental transcerebral fistula. Perineural olfactory CSF flow in the normal, hydrocephalic, and postoperative hydrocephalic dog shown by radionuclide ventriculography. J Neurosurg 61：355-364, 1984

39) Galen C：De anatomics administrationibus. Book IX：On the Brain. Reprint：New York, Oxford University Press, p177

40) Gomez DG, Chambers AA, Di Benedetto AT, Potts DG：The spinal cerebrospinal absorptive pathways. Neuroradiology 8：61-66, 1974

41) Gomez DG, Ehrmann JE, Gordon Potts D, Pavese AM, Gilanian A：The arachnoid granulations of the newborn human：an ultrastructural study. Int J Dev Neurosci 1：139-147, 1983

42) Gomez DG, Manzo RP, Fenstermacher JD, Potts DG：Cerebrospinal fluid absorption in the rabbit. Optic pathways. Graefes Arch Clin Exp Ophthalmo 226：1-7, 1988

43) Greitz D：Paradigm shift in hydrocephalus research in legacy of Dandy's pioneering work：rationale for third ventriculostomy in communicating hydrocephalus. Childs Nerv Syst 23：487-489, 2007

model of cerebrospinal fluid outflow through human arachnoid granulations. Invest Ophthalmol Vis Sci 47：3664-3672, 2006

45) Hammock MK, Milhorat TH：Recent studies on the formation of cerebrospinal fluid. Dev Med Child Neurol Suppl：27-34, 1973

46) 橋本一成：神経系の組織液としての髄液　その循環路（いわゆるマイナーパスウエイー）とその臨床的意義．小児の脳神経29：217-223, 2004

47) Hassin GB：Notes on the nature and origin of the cerebrospinal fluid. J Nerv Dis 59：113-121, 1924

48) Hasuo M, Asano Y, Teraoka M, Ikeyama A, Kageyama N：Cerebrospinal fluid absorption into the lymphatic system in increased intracranial pressure. Abstract 096, The Vth International Symposium on Intracranial Pressure, 1983, p226

49) Heisey SR, Held D, Pappenheimer JR：Bulk flow and diffusion in the cerebrospinal fluid system of the goat. Am J Physiol 203：775-781, 1962

50) Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M：A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 4：147ra111, 2012

51) Jackson RT, Tigges J, Arnold W：Subarachnoid space of the CNS nasal mucosa, and lymphatic system. Arch Otolaryngol 105：180-184, 1979

52) Johanson C, Duncan J, Klinge P, Brinker T, Stopa E, Silverberg G：Multiplici of cerebrospinal fluid functions：new challenges in health and disease. Cerebrospinal Fluid Res 5：10, 2008

53) Johanson CE：Choroid plexus-CSF circulatory dynamics：impact on brain growth, metabolism and repair. In Totowa CP（Ed）Neuroscience in Medicine. The Human Press, New Jersey, 2008, pp173-200

54) Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D：Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates, and other mammalian species. Cerebrospinal Fluid Res 1：2, 2004

55) Kalaria RN, Premkumar DR, Lin CW, Kroon SN, Bae JY, Sayre LM, LaManna JC：Identification and expression of the Na＋/H＋exchanger in mammalian cerebrovascular and choroidal tissues：characterization by amiloride-sensitive［3H］MIA binding and RT-PCR analysis. Brain Res Mol Brain Res 58：178-187, 1998

56) Key A, Retzius G：Studien in der Anatomie des Nervensystems und des Bindegewebes Stockholm：Samsin and Wallen, 1875

57) Kida S, Yamashima T, Kubota T, Ito H, Yamamoto S：A light and electron microscopic and immunohistochemical study of human arachnoid villi. J Neurosurg 69：429-435, 1988

58) Kida S, Pantazis A, Weller RO：CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol 19：480-488, 1993

59) 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 158：1397-1405, 2009

60) Koh L, Zakharov A, Johnston M：Integration of the subarachnoid space and lymphatics：is it time to embrace a new concept of cerebrospinal fluid absorption? Cerebrospinal Fluid Res 2：6, 2005

61) Kozma M, Zoltãn OT, Csillik B：Die anatomischen Grundlagen des pralymphatischen Systems in Gehirn. Acta Anat（Basel）81：409-420, 1972

62) Love JA, Leslie RA：The effects of raised ICP on lymph flow in the cervical lymphatic trunks in cats. J Neurosurg 60：577-581, 1984

63) Maraković J, Oresković D, Rados M, Vukić M, Jurjević I, Chudy D, Klarica M：Effect of osmolarity on CSF volume during ventriculo-aqueductal and ventriculo-cisternal perfusions in cats. Neurosci Lett 484：93-97, 2010

64) Maraković J, Oresković D, Jurjević I, Rados M, Chudy D, Klarica M：Potential error in ventriculocisternal perfusion method for determination of cerebrospinal fluid formation rate in cats. Coll Antropol 35 Suppl 1：73-77, 2011

65) McComb JG, Hyman S, Weiss MH：Lymphatic drainage of cerebrospinal fluid in the cat. In：Hydrocephalus, Shapiro K, Marmarou A, Portony H（eds), Raven Press, New York, 1984, pp83-98

66) Milhorat TH：Choroid plexus and cerebrospinal fluid production. Science 166：1514-1516, 1969

67) Milhorat TH, Hammock MK, Fenstermacher JD, Levin VA：Cerebrospinal fluid production by the choroid plexus and brain. Science 173：330-332, 1971

68) Milhorat TH：The third circulation revisited. J Neurosurg 42：628-645, 1975

69) Milhorat TH：Structure and function of the choroid plexus and other sites of cerebrospinal fluid formation. Int Rev Cytol 47：225-288, 1976

70) Milhorat TH, Hammock MK, Chien T, Davis DA：Normal rate of cerebrospinal fluid formation five years after bilateral choroid plexectomy. Case report. J Neurosurg 44：735-739, 1976

71) Mortensen OA, Sullivan WE：The cerebrospinal fluid and the cervical lymph nodes. Anat Rec 56：359-363, 1933

72) Naidich TP, Epstein F, Lin JP, Kricheff II, Hochwald GM：Evaluation of pediatric hydrocephalus by computed tomography. Radiology 119：337-345, 1976

73) O'Connell JE：Cerebrospinal fluid mechanics. Proc R Soc Med 63：507-518, 1970

74) Oehmichen M, Gencic M：Experimental studies on kinetics and functions of monuclear phagozytes of the central nervous system. Acta Neuropath（Berlin）suppl VI：285-290, 1975

75) Oi S, Di Rocco C：Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain. Childs Nerv Syst 22：662-669, 2006

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

77) Osaka K, Handa H, Matsumoto S, Yasuda M：Development of the cerebrospinal fluid pathway in the normal and abnormal human embryos. Child's Brain 6：26-38, 1980

78) Pollay M, Curl F：Secretion of cerebrospinal fluid by the ventricular ependyma of the rabbit. Am J Physiol 213：1031-1038, 1967

79) Pollay M, Stevens A, Roberts PA：Alteration in choroid plexus blood flow and cerebrospinal fluid formation by increased ventricular pressure. In：Wood JH（Ed), Neurobiology of Cerebrospinal Fluid, vol.2. Plenum Press, New York, 1983, pp687-695

80) Pollay M：The function and structure of the cerebrospinal fluid outflow system. Cerebrospinal Fluid Res 7：9, 2010

81) Raimondi AJ：A unifying theory for the definition and classification of hydrocephalus. Childs Nerv Syst 10：2-12, 1994

82) Renkin EM, Crone C：Microcirculation and capillary exchange. In：Greger R, Windhorst U（Eds), Comprehensive Human Physiology. Springer, Berlin, 1996, pp1965-1979

83) Sahar A, Hochwald GM, Ransohoff J：Alternate pathway for cerebrospinal fluid absorption in animals with experimental obstructive hydrocephalus. Exp Neurol 25：200-206, 1969

84) Sato O, Asai T, Amano Y, Hara M, Tsugane R, Yagi M；Formation of cerebrospinal fluid in spinal subarchnoid apace. Nature 233：129-130, 1971

85) Sato O, Bering EA Jr, Yagi M, Tsugane R, Hara M, Amano Y, Asai T：Bulk flow in the cerebrospinal fluid system of the dog. Acta Neurol Scand 51：1-11, 1975

86) Schwalbe G：Der arachnoidalraum ein lympharaum und sein zusammenhang mir den perichoroidalraum. Zentralbl Med Wiss 7：465, 1869

87) Shulman K, Yarnell P, Ransohoff J：Dural sinus pressure. Arch Neurol 10：575-580, 1964

88) Szentisványi I, Patlak CS, Ellis RA, Cserr HF：Drainage of interstitial fluid from different regions of rat brain. Am J Physiol 246：F835-F844, 1984

89) Tamburrini G, Caldarelli M, Di Rocco F, Massimi L, D'Angelo L, Fasano T, Di Rocco C：The role of endoscopic choroid plexus coagulation in the surgical management of bilateral choroid plexuses hyperplasia. Childs Nerv Syst 22：605-608, 2006

90) Tripathi BJ, Tripathi RC：Vacuolar trancellular channels as a drainage pathway for cerebrospinal fluid. J Physiol 239：195-206, 1974

91) Tripathi R：Tracing the bulk flow route of cerebrospinal fluid by transmission and scanning electron microscopy. Brain Res 80：503-506, 1974

92) Tripathi RC：The functional morphology of the outflow systems of ocular and cerebrospinal fluids. Exp Eye Res 25 suppl：65-116, 1977

93) Tsutsumi S, Ito M, Yasumoto Y, Tabuchi T, Ogino I：The Virchow-Robin spaces：delineation by magnetic resonance imaging with considerations on anatomofunctional implications. Childs Nerv Syst 27：2057-2066, 2011

94) Tsutsumi S, Ogino I, Miyajima M, Nakamura M, Yasumoto Y, Arai H, Ito M：Cranial arachnoid protrusions and contiguous diploic veins in CSF drainage. AJNR Am J Neuroradiol 35：1735-1739, 2014

95) Tubbs RS, Hansasuta A, Stetler W, Kelly DR, Blevins D, Humphrey R, Chua GD, Shoja MM, Loukas M, Oakes WJ：Human spinal arachnoid villi revisited：immnohistological study and review of the literature. J Neurosurg Spine 7：328-331, 2007

96) Weed LH：Studies on cerebro-spinal fluid. No.III：the pathways of escape from the subarachnoid villi. J Med Res 31：51-91, 1914

97) Weed LH：Studies on the cerebro-spinal fluid. No.IV：the dual source of cerebro-spinal fluid. J Med Res 31：93-118, 1914

98) Welch K, Friedman V：The relation between the structure of arachnoid villi and their functions. Surg Forum 10：767-769, 1960

99) Welch K, Pollay M：The spinal arachnoid villi of the monkeys cercopithecus aethiops sabaeus and macaca irus. Anat Rec 145：43-48, 1963

100)Welch K：The secretion of cerebrospinal fluid by lamina epithelialis. Monogr Surg Sci 4：155-192, 1967

101)Weller RO, Mitchell J：Cerebrospinal fluid edema and its sequelae in hydrocephalus. Adv Neurol 28：111-123, 1980

102)Williams MA, McAllister JP, Walker ML, Kranz DA, Bergsneider M, Del Bigio MR, Fleming L, Frim DM, Gwinn K, Kestle JR, Luciano MG, Madsen JR, Oster-Granite ML, Spinella G：Priorities for hydrocephalus research：report from a National Institutes of Health-sponsored workshop. J Neurosurg（5 Suppl）107：345-357, 2007

103)Willis T：Cerebri Anatome：cui accessit nervorum description et usus. London：Tho. Roycroft, Impensis Jo. Martyn ＆ Ja. Allestry；1664

104)Wislocki GB, Putnam TJ：Absorption from the ventricles in experimentally produced internal hydrocephalus. Am J Anat 29：313-320, 1921

105)Yamada S, Miyazaki M, Kanazawa H, Higashi M, Morohoshi Y, Bluml S, McComb JG：Visualization of cerebrospinal fluid movement with spin labeling at MR imaging：preliminary results in normal and pathophysiologic conditions. Radiology 249：644-652, 2008

106)Yamashima T：Ultrastructural study of the final cerebrospinal fluid pathway in human arachnoid villi. Brain Res 384：68-76, 1986