Acta Neuropathologica

, Volume 67, Issue 1–2, pp 96–102 | Cite as

A quantitative study of blood-brain barrier permeability ultrastructure in a new rat glioma model

  • P. A. Stewart
  • K. Hayakawa
  • E. Hayakawa
  • C. L. Farrell
  • R. F. Del Maestro
Original Works

Summary

Cerebral edema, a major complication of tumors in the brain, is the result of an alteration in the blood-brain barrier (B-BB). The vascular ultrastructural changes that underlie edema formation have been described in a variety of tumors. Interendothelial junction abnormalities, fenestrations, and large numbers of tubulo-vesicular profiles in the tumor vascular endothelium have been presumed to represent permeability routes that permit the escape of serum constituents into the tumor, from where they flow into the surrounding brain. Descriptive studies do not provide information on the relative frequency of these presumptive permeability routes.

In the study reported here we have quantified ultrastructural features associated with the B-BB in the vessels of an experimental glioma in rat. We found that approximately 60% of the tumor vessel profiles have junctional abnormalities and 30% have one or more fenestrations. The density of tubulo-vesicular profiles, however, was not increased. In addition, tumor vessel walls were thicker than normal vessels of the same caliber and the mitochondrial density was in the range of that for non-barrier vessels. Vessels in peritumoral regions were not altered in any of the parameters measured.

Key words

Blood-brain barrier Morphometry Ultrastructure Experimental glioma 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bigner DD, Schold C, Bigner SH, Bullard DE, Wikstrand C (1981) How heterogeneous are gliomas? Cancer Treat Rep [Suppl 2] 65:45–49Google Scholar
  2. 2.
    Brightman MW, Hori M, Rapoport SI, Reese TS, Westergaard E (1973) Osmotic opening of tight junctions in cerebral endothelium. J Comp Neurol 152:317–326Google Scholar
  3. 3.
    Bundgaard M (1983) Vesicular transport in capillary endothelium: Does it occur? Fed Proc 42:2425–2430Google Scholar
  4. 4.
    Bundgaard M, Hagman P, Crone C (1983) The three-dimensional organization of plasmalemmal vesicular profiles in the endothelium of rat heart capillaries. Microvasc Res 25:358–368Google Scholar
  5. 5.
    Coomber BL, Stewart PA (1985) Morphometric analysis of CNS microvascular endothelium. Microvasc Res (in press)Google Scholar
  6. 6.
    Coomber BL, Stewart PA (1984) Evaluation of cerebral endothelial vesciles by serial sectioning. Soc Neurosci Abstr 336.10Google Scholar
  7. 7.
    Cox DJ, Pilkington GJ, Lantos PL (1976) The fine structure of blood vessels in ethylnitrosourea-induced tumours of the rat nervous system. With special reference to the breakdown of the blood-brain barrier. Br J Exp Pathol 57:419–430Google Scholar
  8. 8.
    Deane BR, Lantos PL (1981) The vasculature of experimental brain tumours. Part 1: A sequential light and electron microscope study of angiogenesis. J Neurol Sci 49:55–66Google Scholar
  9. 9.
    Deane BR, Lantos PL (1981) The vasculature of experimental brain tumours. Part 2: A quantitative assessment of morphological abnormalities. J Neurol Sci 49:67–77Google Scholar
  10. 10.
    Dorovini-Zis K, Sato M, Goping G, Rapoport S, Brightman M (1983) Ionic lanthanum passage across cerebral endothelium exposed to hyperosmotic arabinose. Acta Neuropathol (Berl) 60:49–60Google Scholar
  11. 11.
    Elfvin L-G (1965) The ultrastructure of the capillary fenestrae in the adrenal medulla of the rat. J Ultrastruct Res 12:687–704Google Scholar
  12. 12.
    Farrell CL, Shivers R (1984) Capillary junctions of the rat are not affected by osmotic opening of the blood-brain barrier. Acta Neuropathol (Berl) 63:179–189Google Scholar
  13. 13.
    Farrell CL, Stewart PA, Del Maestro RF (1984) Unpublished resultsGoogle Scholar
  14. 14.
    Frokjaer-Jensen J (1980) Three-dimensional analysis of plasmalemmal vesicles in endothelial cells. An analysis by serial sectioning of frog mesenteric capillaries. J Ultrastruct Res 73:9–20Google Scholar
  15. 15.
    Hirano A, Ghatak NR, Becker NH, Zimmerman HM (1974) A comparison of the fine structure of small blood vessels in intracranial and retroperitoneal malignant lymphomas. Acta Neuropathol (Berl) 27:93–104Google Scholar
  16. 16.
    Hirano A, Matsui T (1975) Vascular structures in brain tumors. Human Pathol 6:611–621Google Scholar
  17. 17.
    Hossmann K-A, Wechsler W, Wilmes F (1979) Experimental peritumorous edema: Morphological and pathophysiological observations. Acta Neuropathol (Berl) 54:195–203Google Scholar
  18. 18.
    Hossmann K-A, Hurter T, Oschlies U (1983) The effect of dexamethasone on serum protein extravasation and edema development in experimental brain tumors in cat. Acta Neuropathol (Berl) 60:223–231Google Scholar
  19. 19.
    Jones W, O'Morchoe PJ, O'Morchoe CC (1983) The organization of endocytotic vesicles in lymphatic endothelium. Microvasc Res 25:286–299Google Scholar
  20. 20.
    Klatzo I (1967) Neuropathological aspects of brain edema. J Neuropathol Exp Neurol 24:1–13Google Scholar
  21. 21.
    Long DM (1970) Capillary ultrastructure and the blood-brain barrier in human malignant tumors. J Neurosurg 32:127–144Google Scholar
  22. 22.
    Lossinsky AS, Vorbrodt AW, Wisniewski HM (1983) Ultracytochemical studies of vesicular and canalicular transport structures in the injured mammalial blood-brain barrier. Acta Neuropathol (Berl) 61:239–245Google Scholar
  23. 23.
    Molnar P, Blasberg RG, Groothius D, Bigner D, Fenstermacher JD (1983) Regional blood-to-tissue transport in avian sarcoma virus-induced brain tumors. Neurology 33:702–711Google Scholar
  24. 24.
    Murray M, Jones H, Cserr HF, Rall DP (1975) The blood-brain barrier and the ventricular system of Myxine glutinosa. Brain Res 99:17–33Google Scholar
  25. 25.
    Nag S, Robertson DM, Dinsdale H (1977) Cerebral cortical changes in acute experimental hypertension. Lab Invest 36:150–161Google Scholar
  26. 26.
    Nag S, Robertson DM, Dinsdale H (1981) Cerebrovascular permeability in mechanically induced hypertension. Can J Neurol Sci 8:215–220Google Scholar
  27. 27.
    Nag S (1984) Cerebral changes in chronic hypertension: Combined permeability and immunohistochemical studies. Acta Neuropathol (Berl) 62:178–184Google Scholar
  28. 28.
    Nagy Z, Pappius H, Mathieson G, Huttner I (1979) Opening of tight junctions in cerebral endothelium. I. Effect of hyperosmolar mannitol infused through the internal carotid artery. J Comp Neurol 185:569–578Google Scholar
  29. 29.
    Nagy Z, Mathieson G, Huttner I (1979) Opening of tight junctions in cerebral endothelium. II. Effect of pressurepulse-induced acute arterial hypertension. J Comp Neurol 185:579–586Google Scholar
  30. 30.
    Nagy A, Peters H, Huttner I (1984) Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions. Lab Invest 50:313–322Google Scholar
  31. 31.
    Nakagawa Y, Cervos-Navarro J, Artigas J (1984) A possible paracellular route for the resolution of hydrocephalic edema. Acta Neuropathol (Berl) 64:122–128Google Scholar
  32. 32.
    Nishio S, Ohta M, Abe M, Kitamura K (1983) Microvascular abnormalities in ethylnitrosourea (ENU)-induced rat brain tumors: Structural basis for altered blood-brain barrier function. Acta Neuropathol (Berl) 59:1–10Google Scholar
  33. 33.
    Oldendorf WH, Cornford ME, Brown WJ (1976) The large apparent metabolic work capacitiy of the blood-brain barrier. Trans Am Neurol Assoc 101:157–160Google Scholar
  34. 34.
    Reinhold HS, van den Berg-Blok A (1983) Vascularization of experimental brain tumors. In: Nugent J, O'Connor M (eds) Development of the vascular system. Ciba Foundation Symposium 100. Pitman Books, London, pp 100–119Google Scholar
  35. 35.
    Ryan US, Ryan JW, Smith DS, Winkler H (1975) Fenestrated endothelium of the adrenal gland: Freezefracture studies. Tissue Cell 7:181–190Google Scholar
  36. 36.
    Stewart PA, Wiley MJ (1981) Developing nervous tissue induces formation of blood-brain-barrier characteristics in invading endothelial cells: A study using quail-chick transplantation chimeras. Dev Biol 84:183–192Google Scholar
  37. 37.
    Stewart PA, Wiley MJ (1981) Structural and histochemical characteristics of the avian blood-brain barrier. J Comp Neurol 202:157–167Google Scholar
  38. 38.
    Stewart PA, Farrell CL, Del Maestro RF (1984) Unpublished resultsGoogle Scholar
  39. 39.
    Vadot E (1980) Morphometrie ultrastructurale des capillaires retiniens chez le singe. Application a la barrier hematoretinienne. Bull Soc Ophthalmol Fr 2:185–187Google Scholar
  40. 40.
    Vorbrodt AW, Lossinsky AS, Wisniewski HM (1984) Enzyme cytochemistry of blood-brain barrier disturbances. Acta Neuropathol (Berl) [Suppl] VIII:43–57Google Scholar
  41. 41.
    Waggener JD, Beggs JL (1976) Vasculature of neural neoplasms. Adv Neurol 15:27–49Google Scholar
  42. 42.
    Wagner RC, Casley-Smith JR (1981) Endothelial vesicles. Microvasc Res 21:267–298Google Scholar
  43. 43.
    Wagner RC, Casley-Smith JR (1981) The quantitative morphometry of capillaries isolated from fat. Microcirculation 1:177–197Google Scholar
  44. 44.
    Westergaard E, van Deurs B, Brondsted HE (1977) Increased vesicular transfer of horseradish peroxidase across cerebral endothelium, evoked by acute hypertension. Acta Neuropathol (Berl) 37:141–152Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • P. A. Stewart
    • 1
  • K. Hayakawa
    • 1
  • E. Hayakawa
    • 1
  • C. L. Farrell
    • 2
  • R. F. Del Maestro
    • 2
  1. 1.Dept. of AnatomyUniversity of TorontoTorontoCanada
  2. 2.Brain Research Laboratory. Depts. of Biophysics and Clinical Neurological SciencesVictoria HospitalLondonCanada

Personalised recommendations