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Permeability of the arachnoid and pia mater. The role of ion channels in the leptomeningeal physiology

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Abstract

Purpose

The purpose of this paper is to study the ionic permeability of the leptomeninges related to the effect of ouabain (sodium–potassium–ATPase inhibitor) and amiloride (epithelial sodium channel (ENaC) inhibitor) on the tissue, as well as identify the presence of ion channels.

Methods

Cranial leptomeningeal samples from 26 adult sheep were isolated. Electrophysiological measurements were performed with Ussing system and transmembrane resistance values (RTM in Ω*cm2) obtained over time. Experiments were conducted with the application of ouabain 10−3 M or amiloride 10−5 M at the arachnoidal and pial sides. Immunohistochemical studies of leptomeningeal tissue were prepared with alpha-1 sodium–potassium–ATPase (ATP1A1), beta-ENaC, and delta-ENaC subunit antibodies.

Results

The application of ouabain at the arachnoidal side raised the transmembrane resistance statistically significantly and thus decreased its ionic permeability. The addition of ouabain at the pial side led also to a significant but less profound increment in transmembrane resistance. The addition of amiloride at the arachnoidal or pial side did not produce any statistical significant change in the RTM from controls (p > 0.05). Immunohistochemistry confirmed the presence of the ATP1A1 and beta- and delta-ENaC subunits at the leptomeninges.

Conclusions

In summary, leptomeningeal tissue possesses sodium–potassium–ATPase and ENaC ion channels. The application of ouabain alters the ionic permeability of the leptomeninges thus reflecting the role of sodium–potassium–ATPase. Amiloride application did not alter the ionic permeability of leptomeninges possibly due to localization of ENaC channels towards the subarachnoid space, away from the experimental application sites. The above properties of the tissue could potentially be related to cerebrospinal fluid turnover at this interface.

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References

  1. Cserr HF (1971) Physiology of the choroid plexus. Physiol Rev 51:273–311

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Segal MB, Pollay M (1977) The secretion of cerebrospinal fluid. Exp Eye Res 25(Suppl):127–148

    Article  PubMed  CAS  Google Scholar 

  4. Segal MB (1993) Extracellular and cerebrospinal fluids. J Inherit Metab Dis 16:617–638

    Article  PubMed  CAS  Google Scholar 

  5. Damkier HH, Brown PD, Praetorius J (2010) Epithelial pathways in choroid plexus electrolyte transport. Physiol Bethesda 25:239–249

    Article  CAS  Google Scholar 

  6. Filippidis AS, Kalani MY, Rekate HL (2011) Hydrocephalus and aquaporins: lessons learned from the bench. Child Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg 27:27–33

    Article  Google Scholar 

  7. Pollay M, Hisey B, Reynolds E, Tomkins P, Stevens FA, Smith R (1985) Choroid plexus Na+/K+-activated adenosine triphosphatase and cerebrospinal fluid formation. Neurosurgery 17:768–772

    Article  PubMed  CAS  Google Scholar 

  8. Amin MS, Reza E, Wang H, Leenen FH (2009) Sodium transport in the choroid plexus and salt-sensitive hypertension. Hypertension 54:860–867

    Article  PubMed  CAS  Google Scholar 

  9. Johanson CE, Duncan JA 3rd, Klinge PM, Brinker T, Stopa EG, Silverberg GD (2008) Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cereb Fluid Res 5:10

    Article  Google Scholar 

  10. Redzic ZB, Segal MB (2004) The structure of the choroid plexus and the physiology of the choroid plexus epithelium. Adv Drug Deliv Rev 56:1695–1716

    Article  PubMed  CAS  Google Scholar 

  11. Alcolado R, Weller RO, Parrish EP, Garrod D (1988) The cranial arachnoid and pia mater in man: anatomical and ultrastructural observations. Neuropathol Appl Neurobiol 14:1–17

    Article  PubMed  CAS  Google Scholar 

  12. Barshes N, Demopoulos A, Engelhard HH (2005) Anatomy and physiology of the leptomeninges and CSF space. Cancer Treat Res 125:1–16

    Article  PubMed  Google Scholar 

  13. Jayatilaka AD (1965) An electron microscopic study of sheep arachnoid granulations. J Anat 99:635–649

    PubMed  CAS  Google Scholar 

  14. McLone DG (1980) The subarachnoid space: a review. Childs Brain 6:113–130

    PubMed  CAS  Google Scholar 

  15. Weller RO (2005) Microscopic morphology and histology of the human meninges. Morphol 89:22–34

    Article  CAS  Google Scholar 

  16. Hatzoglou CH, Gourgoulianis KI, Molyvdas PA (2001) Effects of SNP, ouabain, and amiloride on electrical potential profile of isolated sheep pleura. J Appl Physiol 90:1565–1569

    PubMed  CAS  Google Scholar 

  17. Payne DK, Kinasewitz GT, Gonzalez E (1988) Comparative permeability of canine visceral and parietal pleura. J Appl Physiol 65:2558–2564

    PubMed  CAS  Google Scholar 

  18. Sarkos S, Hatzoglou C, Dahabre J, Gourgoulianis KI, Molyvdas PA (2002) Effect of amiloride in human and sheep parietal pleura. Respir Physiol Neurobiol 132:233–237

    Article  PubMed  CAS  Google Scholar 

  19. Zarogiannis S, Hatzoglou C, Stefanidis I, Ioannou M, Paraskeva E, Gourgoulianis K, Molyvdas PA (2007) Comparison of the electrophysiological properties of the sheep isolated costal and diaphragmatic parietal pleura. Clin Exp Pharmacol Physiol 34:129–131

    Article  PubMed  CAS  Google Scholar 

  20. Zarogiannis S, Hatzoglou C, Stefanidis I, Liakopoulos V, Gourgoulianis K, Molyvdas PA (2007) Adrenergic influence on the permeability of sheep diaphragmatic parietal pleura. Respiration 74:118–120

    PubMed  Google Scholar 

  21. Zarogiannis S, Deligiorgi T, Stefanidis I, Liakopoulos V, Gourgoulianis K, Molyvdas PA, Hatzoglou C (2009) Dexamethasone decreases the transmesothelial electrical resistance of the parietal and visceral pleura. J Physiol Sci 59:335–339

    Article  PubMed  CAS  Google Scholar 

  22. Li FK, To CH, Leung JK, Chan TM, Lai KN (2001) Electrophysiology and glucose transport of human peritoneal mesothelial cells: implications for peritoneal dialysis. Perit Dial Int 21:115–121

    PubMed  CAS  Google Scholar 

  23. Simon M (1996) Peritoneal mesothelium in vitro: an electrophysiologic study. Perit Dial Int 16:393–397

    PubMed  CAS  Google Scholar 

  24. Stefanidis I, Liakopoulos V, Kourti P, Zarogiannis S, Poultsidi A, Mertems PR, Salmas M, Hatzoglou C, Gourgoulianis K, Molyvdas PA (2007) Amiloride-sensitive sodium channels on the parietal human peritoneum: evidence by Ussing-type chamber experiments. ASAIO J 53:335–338

    Article  PubMed  CAS  Google Scholar 

  25. Zarogiannis S, Kourti P, Hatzoglou C, Liakopoulos V, Poultsidi A, Gourgoulianis K, Molyvdas PA, Stefanidis I (2005) Influence of the sodium transport inhibition by amiloride on the transmesothelial resistance of isolated visceral sheep peritoneum. Adv Perit Dial 21:5–8

    PubMed  CAS  Google Scholar 

  26. Zarogiannis S, Liakopoulos V, Hatzoglou C, Kourti P, Vogiatzidis K, Potamianos S, Eleftheriadis T, Gourgoulianis K, Molyvdas PA, Stefanidis I (2007) Effect of sodium-potassium pump inhibition by ouabain on the permeability of isolated visceral sheep peritoneum. Adv Perit Dial 23:43–47

    PubMed  CAS  Google Scholar 

  27. Zarogiannis S, Vogiatzidis K, Hatzoglou C, Liakopoulos V, Potamianos S, Eleftheriadis T, Dovas S, Kourti P, Gourgoulianis K, Molyvdas PA, Stefanidis I (2007) mu-opioid stimulation of isolated parietal sheep peritoneum decreases peritoneal permeability in vitro. Adv Perit Dial 23:34–37

    PubMed  CAS  Google Scholar 

  28. Vogiatzidis K, Hatzoglou C, Zarogiannis S, Matafia G, Gourgoulianis K, Molyvdas PA (2006) mu-opioid influence on transmesothelial resistance of isolated sheep pleura and parietal pericardium. Eur J Pharmacol 530:276–280

    Article  PubMed  CAS  Google Scholar 

  29. Adams EA, Choi HM, Cheung CY, Brace RA (2005) Comparison of amniotic and intramembranous unidirectional permeabilities in late-gestation sheep. Am J Obstet Gynecol 193:247–255

    Article  PubMed  CAS  Google Scholar 

  30. Verikouki CH, Hatzoglou CH, Gourgoulianis KI, Molyvdas PA, Kallitsaris A, Messinis IE (2008) Rapid effect of progesterone on transepithelial resistance of human fetal membranes: evidence for non-genomic action. Clin Exp Pharmacol Physiol 35:174–179

    PubMed  CAS  Google Scholar 

  31. Filippidis A, Zarogiannis S, Ioannou M, Gourgoulianis K, Molyvdas PA, Hatzoglou C (2010) Transmembrane resistance and histology of isolated sheep leptomeninges. Neurol Res 32:205–208

    Article  PubMed  Google Scholar 

  32. Key A, Retzius G (1876) Studien in der Anatomie des Nervensystems und des Bindwebes. Samson and Wallin, Stockholm

    Google Scholar 

  33. Snell R (2006) Clinical neuroanatomy. Lippincot Williams & Wilkins, Philadelphia

    Google Scholar 

  34. Li H, Sheppard DN, Hug MJ (2004) Transepithelial electrical measurements with the Ussing chamber. J Cyst Fibros 3(Suppl 2):123–126

    Article  PubMed  CAS  Google Scholar 

  35. Ussing HH, Zerahn K (1951) Active transport of sodium as the source of electric current in the short-circuited isolated frog skin. Acta Physiol Scand 23:110–127

    Article  PubMed  CAS  Google Scholar 

  36. Zarogiannis S, Hatzoglou C, Stefanidis I, Matafia G, Vogiatzidis K, Gourgoulianis K, Molyvdas PA (2006) Effect of adrenaline on transmesothelial resistance of isolated sheep pleura. Respir Physiol Neurobiol 150:165–172

    Article  PubMed  CAS  Google Scholar 

  37. Zarogiannis S, Gourgoulianis K, Molyvdas PA, Hatzoglou C (2008) Existence of Na(+)-K(+) ATPase in sheep visceral and parietal pleura. Respir Physiol Neurobiol 164:289, author reply 290

    Article  PubMed  CAS  Google Scholar 

  38. Halperin J, Schaeffer R, Galvez L, Malave S (1983) Ouabain-like activity in human cerebrospinal fluid. Proc Natl Acad Sci U S A 80:6101–6104

    Article  PubMed  CAS  Google Scholar 

  39. Halperin JA, Martin AM, Malave S (1985) Increased digitalis-like activity in human cerebrospinal fluid after expansion of the extracellular fluid volume. Life Sci 37:561–566

    Article  PubMed  CAS  Google Scholar 

  40. Halperin JA, Riordan JF, Tosteson DC (1988) Characteristics of an inhibitor of the Na+/K+ pump in human cerebrospinal fluid. J Biol Chem 263:646–651

    PubMed  CAS  Google Scholar 

  41. Halperin JA (1989) Digitalis-like properties of an inhibitor of the Na+/K+ pump in human cerebrospinal fluid. J Neurol Sci 90:217–230

    Article  PubMed  CAS  Google Scholar 

  42. Garty H (1994) Molecular properties of epithelial, amiloride-blockable Na+ channels. FASEB J 8:522–528

    PubMed  CAS  Google Scholar 

  43. Mutsaers SE (2004) The mesothelial cell. Int J Biochem Cell Biol 36:9–16

    Article  PubMed  CAS  Google Scholar 

  44. Nie HG, Tucker T, Su XF, Na T, Peng JB, Smith PR, Idell S, Ji HL (2009) Expression and regulation of epithelial Na+ channels by nucleotides in pleural mesothelial cells. Am J Respir Cell Mol Biol 40:543–554

    Article  PubMed  CAS  Google Scholar 

  45. Drumm ML, Konstan MW, Schluchter MD, Handler A, Pace R, Zou F, Zariwala M, Fargo D, Xu A, Dunn JM, Darrah RJ, Dorfman R, Sandford AJ, Corey M, Zielenski J, Durie P, Goddard K, Yankaskas JR, Wright FA, Knowles MR (2005) Genetic modifiers of lung disease in cystic fibrosis. N Engl J Med 353:1443–1453

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Mr. Ioannis Makadasis for technical assistance.

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The authors have nothing to disclose.

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Correspondence to Aristotelis S. Filippidis or Chrissi Hatzoglou.

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Filippidis, A.S., Zarogiannis, S.G., Ioannou, M. et al. Permeability of the arachnoid and pia mater. The role of ion channels in the leptomeningeal physiology. Childs Nerv Syst 28, 533–540 (2012). https://doi.org/10.1007/s00381-012-1688-x

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  • DOI: https://doi.org/10.1007/s00381-012-1688-x

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