Direct venous spinal reabsorption of cerebrospinal fluid: a new concept with serial magnetic resonance cisternography in rabbits

Laboratory investigation

View More View Less
  • 1 Departments of Neurosurgery and
  • 2 Neuroradiology, Cerrahpasa Medical Faculty, Istanbul University;
  • 3 Department of Radiology, Haseki Training and Research Hospital; and
  • 4 Department of Radiology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
Restricted access

Purchase Now

USD  $45.00

Spine - 1 year subscription bundle (Individuals Only)

USD  $369.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

Object

For nearly 100 years it has been believed that the main reabsorption of CSF occurs in arachnoid projections into the superior sagittal sinus, but a significant number of experiments and cases conflict with this hypothesis. According to recently published studies, CSF is permanently produced and absorbed in the whole CSF system. Clusters of arachnoidal villi, which are speculated to have a role in the reabsorption of CSF, have recently been revealed in the dorsal root of the spinal nerves. Huge absorptive surface areas of microvessels have been suggested to serve a putative role in reabsorption. The authors' aim was to observe direct venous connections between the subarachnoid space and the perispinal veins.

Methods

Eleven adult (6 months old) New Zealand white male rabbits weighing approximately 3.0 kg each were used in this experiment. After obtaining precontrast MR cisternography images, subarachnoid access was gained percutaneously via a cisternal approach by using a 20-gauge intravenous indwelling cannula. One rabbit died as a result of brainstem trauma during percutaneous cannulation before contrast administration, but contrast agent was still injected to see the possible MR imaging results of spinal CSF reabsorption after death. Magnetic resonance imaging was performed at 15, 60, 120, and 180 minutes after the administration of contrast agent. After intramuscular injections of anesthetic, 2 rabbits died 120 and 150 minutes after contrast injection, but the MR imaging study at 180 minutes after contrast injection was still performed.

Results

Direct connections between the subarachnoid space and the perispinal veins were observed in all rabbits during serial MR cisternography. The enhancement power was not affected by the amount of injected contrast agent or by cervical or lumbar penetration but was increased at higher contrast concentrations or upon seizure (physical activity).

Conclusions

Extracranial reabsorption of CSF has been finally proved with direct radiological confirmation of spinal venous reabsorption of CSF using serial MR cisternography. The authors believe that this study can help to develop a more accurate model of CSF dynamics, which will allow understanding of many CSF-related diseases, as well as the development of new strategies for treatment.

Spine - 1 year subscription bundle (Individuals Only)

USD  $369.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address correspondence to: Huseyin Biceroglu, M.D., Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, 34098 K.M.Pasa Istanbul, Turkey. email: huseyin.biceroglu@gmail.com.

Please include this information when citing this paper: published online January 13, 2012; DOI: 10.3171/2011.12.SPINE11108.

  • 1

    Boulton M, , Armstrong D, , Flessner M, , Hay J, , Szalai JP, & Johnston M: Raised intracranial pressure increases CSF drainage through arachnoid villi and extracranial lymphatics. Am J Physiol 275:R889R896, 1998

    • Search Google Scholar
    • Export Citation
  • 2

    Boulton M, , Flessner M, , Armstrong D, , Hay J, & Johnston M: Lymphatic drainage of the CNS: effects of lymphatic diversion/ligation on CSF protein transport to plasma. Am J Physiol 272:R1613R1619, 1997

    • Search Google Scholar
    • Export Citation
  • 3

    Boulton M, , Flessner M, , Armstrong D, , Mohamed R, , Hay J, & Johnston M: Contribution of extracranial lymphatics and arachnoid villi to the clearance of a CSF tracer in the rat. Am J Physiol 276:R818R823, 1999

    • Search Google Scholar
    • Export Citation
  • 4

    Bozanovic-Sosic R, , Mollanji R, & Johnston MG: Spinal and cranial contributions to total cerebrospinal fluid transport. Am J Physiol Regul Integr Comp Physiol 281:R909R916, 2001

    • Search Google Scholar
    • Export Citation
  • 5

    Bradbury M: Lymphatics and central nervous system. Trends Neurosci 4:100101, 1981

  • 6

    Bradbury MW, & Cole DF: The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humour. J Physiol 299:353365, 1980

    • Search Google Scholar
    • Export Citation
  • 7

    Bradbury MW, & Cserr HF, Drainage of cerebral interstitial fluid and of cerebrospinal fluid into lymphatics. Johnston M: Experimental Biology of the Lymphatic Circulation New York, Elsevier, 1985. 355349

    • Search Google Scholar
    • Export Citation
  • 8

    Bradbury MW, , Cserr HF, & Westrop RJ: Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit. Am J Physiol 240:F329F336, 1981

    • Search Google Scholar
    • Export Citation
  • 9

    Bradbury MW, , Deane R, , Segal MB, & Westrop RJ: Recovery of [125I]albumin in deep cervical lymph of the sheep after intraventricular injection. J Physiol 305:Suppl 52P, 1980

    • Search Google Scholar
    • Export Citation
  • 10

    Bradbury MW, & Westrop RJ: Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit. J Physiol 339:519534, 1983

    • Search Google Scholar
    • Export Citation
  • 11

    Bradford FK, & Johnson PCJ Jr: Passage of intact ironlabeled erythrocytes from subarachnoid space to systemic circulation in dogs. J Neurosurg 19:332336, 1962

    • Search Google Scholar
    • Export Citation
  • 12

    Brierley JB: The penetration of particulate matter from the cerebrospinal fluid into the spinal ganglia, peripheral nerves, and perivascular spaces of the central nervous system. J Neurol Neurosurg Psychiatry 13:203215, 1950

    • Search Google Scholar
    • Export Citation
  • 13

    Brierly JB, & Field EJ: The connexions of the spinal sub-arachnoid space with the lymphatic system. J Anat 82:153166, 1948

  • 14

    Brinker T, , Lüdemann W, , Berens von Rautenfeld D, & Samii M: Dynamic properties of lymphatic pathways for the absorption of cerebrospinal fluid. Acta Neuropathol 94:493498, 1997

    • Search Google Scholar
    • Export Citation
  • 15

    Bulat M, & Klarica M: Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev 65:99112, 2011

  • 16

    Dandy WE: Where is cerebrospinal fluid absorbed?. JAMA 92:20122014, 1929

  • 17

    d'Avella D, , Cicciarello R, , Albiero F, & Andrioli G: Scanning electron microscope study of human arachnoid villi. J Neurosurg 59:620626, 1983

    • Search Google Scholar
    • Export Citation
  • 18

    Edsbagge M, , Tisell M, , Jacobsson L, & Wikkelso C: Spinal CSF absorption in healthy individuals. Am J Physiol Regul Integr Comp Physiol 287:R1450R1455, 2004

    • Search Google Scholar
    • Export Citation
  • 19

    Elman R: Spinal arachnoid granulations with special reference to the cerebrospinal fluid. Johns Hopkins Hosp Bull 34:99104, 1923

  • 20

    Erlich SS, , McComb JG, , Hyman S, & Weiss MH: Ultrastructural morphology of the olfactory pathway for cerebrospinal fluid drainage in the rabbit. J Neurosurg 64:466473, 1986

    • Search Google Scholar
    • Export Citation
  • 21

    Field EJ, & Brierley JB: The anatomy of the spinal nerve root lymphatic drainage. J Anat 83:76, 1949

  • 22

    Fishman RA: Factors influencing the exchange of sodium between plasma and cerebrospinal fluid. J Clin Invest 38:16981708, 1959

  • 23

    Gomez DG, , Chambers AA, , Di Benedetto AT, & Potts DG: The spinal cerebrospinal fluid absorptive pathways. Neuroradiology 8:6166, 1974

  • 24

    Gomez DG, , Fenstermacher JD, , Manzo RP, , Johnson D, & Potts DG: Cerebrospinal fluid absorption in the rabbit: olfactory pathways. Acta Otolaryngol 100:429436, 1985

    • Search Google Scholar
    • Export Citation
  • 25

    Greitz D, & Hannerz J: A proposed model of cerebrospinal fluid circulation: observations with radionuclide cisternography. AJNR Am J Neuroradiol 17:431438, 1996

    • Search Google Scholar
    • Export Citation
  • 26

    Holtz E, , Michelet AA, & Jacobsen T: Absorption after subarachnoid and subdural administration of iohexol, 51Cr-EDTA, and 125I-albumin to rabbits. AJNR Am J Neuroradiol 4:338341, 1983

    • Search Google Scholar
    • Export Citation
  • 27

    Jackson RT, , Tigges J, & Arnold W: Subarachnoid space of the CNS, nasal mucosa, and lymphatic system. Arch Otolaryngol 105:180184, 1979

  • 28

    Johnston M, , Armstrong D, & Koh L: Possible role of the cavernous sinus veins in cerebrospinal fluid absorption. Cerebrospinal Fluid Res 16:3, 2007

    • Search Google Scholar
    • Export Citation
  • 29

    Johnston M, & Papaiconomou C: Cerebrospinal fluid transport: a lymphatic perspective. News Physiol Sci 17:227230, 2002

  • 30

    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

    • Search Google Scholar
    • Export Citation
  • 31

    Kelkenberg U, , von Rautenfeld DB, , Brinker T, & Hans VH: Chicken arachnoid granulations: a new model for cerebrospinal fluid absorption in man. Neuroreport 12:553557, 2001

    • Search Google Scholar
    • Export Citation
  • 32

    Kida S, , Yamashima T, , Kubota T, , Ito H, & Yamamoto S: A light and electron microscopic and immunohistochemical study of human arachnoid villi. J Neurosurg 69:429435, 1988

    • Search Google Scholar
    • Export Citation
  • 33

    Kido DK, , Gomez DG, , Pavese AM Jr, & Potts DG: Human spinal arachnoid villi and granulations. Neuroradiology 11:221228, 1976

  • 34

    Klarica M, , Varda R, , Vukić M, , Oresković D, , Rados M, & Bulat M: Spinal contribution to CSF pressure lowering effect of mannitol in cats. Acta Neurochir Suppl (Wien) 95:407410, 2005

    • Search Google Scholar
    • Export Citation
  • 35

    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

    • Search Google Scholar
    • Export Citation
  • 36

    Koh L, , Zakharov A, , Nagra G, , Armstrong D, , Friendship R, & Johnston M: Development of cerebrospinal fluid absorption sites in the pig and rat: connections between the subarachnoid space and lymphatic vessels in the olfactory turbinates. Anat Embryol (Berl) 211:335344, 2006

    • Search Google Scholar
    • Export Citation
  • 37

    Massicotte EM, & Del Bigio MR: Human arachnoid villi response to subarachnoid hemorrhage: possible relationship to chronic hydrocephalus. J Neurosurg 91:8084, 1999

    • Search Google Scholar
    • Export Citation
  • 38

    Orešković D, & Klarica M: The formation of cerebrospinal fluid: Nearly a hundred years of interpretations and misinterpretations. Brain Res Rev 64:241262, 2010

    • Search Google Scholar
    • Export Citation
  • 39

    Papaiconomou C, , Bozanovic-Sosic R, , Zakharov A, & Johnston M: Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or extracranial lymphatics?. Am J Physiol Regul Integr Comp Physiol 283:R869R876, 2002

    • Search Google Scholar
    • Export Citation
  • 40

    Papaiconomou C, , Zakharov A, , Azizi N, , Djenic J, & Johnston M: Reassessment of the pathways responsible for cerebrospinal fluid absorption in the neonate. Childs Nerv Syst 20:2936, 2004

    • Search Google Scholar
    • Export Citation
  • 41

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

  • 42

    Rexed BA, & Wennstrom KG: Arachnoidal proliferation and cystic formation in the spinal nerve-root pouches of man. J Neurosurg 16:7384, 1959

    • Search Google Scholar
    • Export Citation
  • 43

    Shabo AL, & Maxwell DS: Electron microscopic observations on the fate of particulate matter in the cerebrospinal fluid. J Neurosurg 29:464474, 1968

    • Search Google Scholar
    • Export Citation
  • 44

    Tubbs RS, , Hansasuta A, , Stetler W, , Kelly DR, , Blevins D, & Humphrey R, : Human spinal arachnoid villi revisited: immunohistological study and review of the literature. J Neurosurg Spine 7:328331, 2007

    • Search Google Scholar
    • Export Citation
  • 45

    Walter BA, , Valera VA, , Takahashi S, & Ushiki T: The olfactory route for cerebrospinal fluid drainage into the peripheral lymphatic system. Neuropathol Appl Neurobiol 32:388396, 2006

    • Search Google Scholar
    • Export Citation
  • 46

    Weed LH: Studies on cerebro-spinal fluid. No II: The theories of drainage of cerebro-spinal fluid with an analysis of the methods of investigation. J Med Res 31:2149, 1914

    • Search Google Scholar
    • Export Citation
  • 47

    Weed LH: Studies on cerebro-spinal fluid. No III: The pathways of escape from the subarachnoid spaces with particular reference to the arachnoid villi. J Med Res 31:5191, 1914

    • Search Google Scholar
    • Export Citation
  • 48

    Wegefarth P, & Weed LH: Studies on cerebro-spinal fluid. No VII: The analogous processes of the cerebral and ocular fluids. J Med Res 31:167176, 1914

    • Search Google Scholar
    • Export Citation
  • 49

    Welch K, & Pollay M: The spinal arachnoid villi of the monkeys Cercopithecus aethiops sabaeus and Macaca irus. Anat Rec 145:4348, 1963

  • 50

    Wislocki GB, The cytology of the cerebrospinal fluid pathways. Cowdry EV: Special Cytology ed 3 New York, Hoeber, Vol III:1932. 14851521

    • Search Google Scholar
    • Export Citation
  • 51

    Woollam DH, & Millen JW: An anatomical approach to poliomyelitis. Lancet 1:364367, 1953

  • 52

    Zakharov A, , Papaiconomou C, & Johnston M: Lymphatic vessels gain access to cerebrospinal fluid through unique association with olfactory nerves. Lymphat Res Biol 2:139146, 2004

    • Search Google Scholar
    • Export Citation
  • 53

    Zakharov A, , Papaiconomou C, , Koh L, , Djenic J, , Bozanovic-Sosic R, & Johnston M: Integrating the roles of extracranial lymphatics and intracranial veins in cerebrospinal fluid absorption in sheep. Microvasc Res 67:96104, 2004

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 762 87 6
Full Text Views 82 13 0
PDF Downloads 155 12 0
EPUB Downloads 0 0 0