Skip to main content
Log in

Microvascular abnormalities in ethylnitrosourea (ENU)-induced rat brain tumors: Structural basis for altered blood-brain barrier function

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

The fine structure, histometric characteristics, and permeability of microvessels were studied by electron microscopy in normal and in ethylnitrosourea (ENU)-induced glioma tissue from rats, using horseradish peroxidase (HRP) as a tracer. The tumor vessels were classified into (1) capillary buds (Type I); (2) round small to large capillaries (Type II); (3) sinusoidal or venule-like microvessels (Type III), and (4) abnormal arteriole-like microvessels (Type IV). All endothelial cells, basement membranes and periendothelial cells in the tumor tissue demonstrated changes in structure. The most striking alterations occurred in the endothelial cells; there were abnormal endothelial tight junctions, altered pinocytotic activity, and thickening. In the tracer study, the reaction product of HRP was present around some sinusoidal or venule-like microvessels (Type III) and extended to the widened extracellular spaces around the microvessels. The endothelial cells of Type III microvessels showed decreased nuclear and mitochondrial fractions, and increased euchromatin content and a rough endoplasmic reticulum fraction. The pinocytotic vesicles with the HRP reaction product in the endothelial cells were not increased in number. Fenestrations and gaps of the endothelial cells were observed. These alterations of the endothelial cells of sinusoidal or venule-like microvessels (Type III) are considered to be the main cause of breakdown of the blood-brain barrier in this tumor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Abe M (1982)12B compound distribution in rat tissue of transplanted and ethylnitrosourea-induced brain tumors. Eukuoka Acta Med 73:250–271

    Google Scholar 

  2. Bär Th, Wolff JR (1976) Development and adult variations of the wall of brain capillaries in the neocortex of rat and cat. In: Cervós-Navarro J, Betz E, Matakas F, Wüllenwer R (eds) The cerebral vessel wall. Raven Press, New York, pp 1–6

    Google Scholar 

  3. Blank NK, Yung W, Vick NA (1976) Blood vessels and “blood channels” in experimental viral-induced mammalian gliomas. J Neuropathol Exp Neurol 35:102–103

    Google Scholar 

  4. Brightman MW, Klatzo I, Olsson Y, Reese TS (1970) The blood-brain barrier under normal and pathological conditions. J Neurol Sci 10:215–239

    Google Scholar 

  5. Brightman M, Prescott L, Kirschestein R (1972) Cytological features pertaining to the distribution of exogeneous peroxidase in Simian virus 40-induced brain tumors. J Neuropathol Exp Neurol 31:177

    Google Scholar 

  6. Brightman MW, Reese TS, Vick NA, Bigner DD (1971) A mechanism underlying the lack of a blood-brain-barrier to peroxidase in virally induced brain tumors. J Neuropathol Exp Neurol 30:139–140

    Google Scholar 

  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 57:419–430

    Google Scholar 

  8. Dean BR, Lantos PL (1981) The vasculature of experimental brain tumours. Part 1. A sequential light and electron microscope study of angiogenesis. J Neurol Sci 49:55–66

    Google Scholar 

  9. Dean BR, Lantos PL (1981) The vasculature of experimental brain tumours. Part 2. A quantitative assessment of morphological abnormalities. J Neurol Sci 49:67–77

    Google Scholar 

  10. Deurs B (1977) Vesicular transport of horseradish peroxidase from brain to blood in segments of cerebral microvasculature in adult mice. Brain Res 124:1–8

    Google Scholar 

  11. Eriksson E, Zarem HA (1977) Growth and differentiation of blood vessels. In: Kaley G, Altara BM (eds) Microvasculation, vol 1. University Park Press, Baltimore London Tokyo, pp 393–419

    Google Scholar 

  12. Frenster JH, Allfrey VG, Mirsky AE (1963) Repressed and activated chromatin isolated from interphase lymphocytes. Proc Natl Acad Sci USA 50:1026–1032

    Google Scholar 

  13. Grammas P, Giacomelli F, Wiener J (1981) Carotid artery constriction in acute hypertension. Am J Pathol 103:226–233

    Google Scholar 

  14. Hally AD (1964) A counting method for measuring the volumes of tissue components in microscopical sections. Q J Microsc Sci 105:503–517

    Google Scholar 

  15. Hara H, Enzan H, Moriki T, Miyao M, Yamane T (1981) Electron microscopic localization of acridine organe binding DNA within rat brain tumor cells. Igaku no Ayumi 177:366–368

    Google Scholar 

  16. Hirano A, Becker NH, Zimmerman HM (1970) The use of peroxidase as a tracer in studies of alterations in the blood-brain barrier. J Neurol Sci 10:205–213

    Google Scholar 

  17. Hirano A, Matsui T (1975) Vascular structures in brain tumors. Hum Pathol 6:611–621

    Google Scholar 

  18. Hirano A, Tomiyasu U, Zimmerman HM (1972) The fine structure of blood vessels in chromophobe adenoma. Acta Neuropathol (Berl) 22:200–207

    Google Scholar 

  19. Hirano A, Zimmerman HM (1972) Fenestrated blood vessels in a metastatic renal carcinoma in the brain. Lab Invest 26:465–468

    Google Scholar 

  20. Jacobs JM, Macfarlane RM, Cavanagh JB (1976) Vascular leakage in the dorsal root ganglia of the rat, studied with horseradish peroxidase. J Neurol Sci 29:95–107

    Google Scholar 

  21. Long DM (1970) Capillary ultrastructure and the blood-brain barrier in human malignant brain tumors. J Neurosurg 32:127–144

    Google Scholar 

  22. Luse SA (1960) Electron microscopic study of brain tumors. Neurology 10:881–905

    Google Scholar 

  23. Mitchell J, Weller RO, Evans H (1979) Re-establishment of the blood-brain barrier to peroxidase following cold injury to mouse cortex. Acta Neuropathol (Berl) 46:45–49

    Google Scholar 

  24. Moriyasu N, Nakamura S, Miyagami M, Morisawa S, Igusa N (1971) The fine structure of capillary in the brain tumors. J Clin Elec Microsc 4:771–784

    Google Scholar 

  25. Movat HZ, Fernando NVP (1964) The fine structure of the terminal vascular bed. IV. The venules and their perivascular cells (pericytes, adventitial cells). Exp Mol Pathol 3:98–114

    Google Scholar 

  26. O'Connor JS, Laws ER Jr (1969) Changes in histochemical stainings of brain tumor blood vessels associated with increasing malignancy. Acta Neuropathol (Berl) 14:161–173

    Google Scholar 

  27. Oldendorf WH, Cornford ME, Brown WJ (1977) The large apparent work capability of the blood-brain barrier: A study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol 1:409–417

    Google Scholar 

  28. Palade GE, Simionescu M, Simionescu N (1979) Structural aspects of the permeability of the microvascular endothelium. Acta Physiol Scand (Suppl) 463:11–32

    Google Scholar 

  29. Pappas GD (1970) Some morphological considerations of the blood-brain barrier. J Neurol Sci 10:241–246

    Google Scholar 

  30. Povlishock JT, Becker DP, Miller JD, Jenkins LW, Dietrich WD (1979) The morphopathologic substrates of concussion? Acta Neuropathol (Berl) 47:1–11

    Google Scholar 

  31. Raimondi AJ (1964) Localization of radio-iodinated serum albumin in human glioma. Arch Neurol 11:173–184

    Google Scholar 

  32. Raimondi AJ, Mullan S, Evans JP (1962) Human brain tumors: An electron-microscopic study. J Neurosurg 19:731–751

    Google Scholar 

  33. Rhodin JAG (1968) Ultrastructure of mammalian veneous capillaries, venules, and small collecting veins. J Ultrastruct Res 25:452–500

    Google Scholar 

  34. Russell DS, Rubinstein LJ (1977) Pathology of tumours of the nervous system, 4th edn. E Arnold, London

    Google Scholar 

  35. Schiffer D, Giordana MT, Mauro A, Racagni G, Bruno F, Pezzotaa S, Paoletti P (1980) Experimental brain tumors by transplacental ENU. Multifactorial study of the latency period. Acta Neuropathol (Berl) 49:117–122

    Google Scholar 

  36. Simionescu N, Simionescu M, Palade GE (1978) Open junctions in the endothelium of the postcapillary venules of the diaphragm. J Cell Biol 79:27–44

    Google Scholar 

  37. Taomoto K, Fujiwara K, Tamaki N, Matsumoto S (1978) Experimental brain tumors produced transplacentally by ethylnitrosourea (IV): Ultrastructure studied by using transmission and scanning electron microscope. Brain Nerve (Tokyo) 30: 911–921

    Google Scholar 

  38. Tsuchida T (1974) A study of capillary ultrastructure of brain tumors in association with blood-brain barrier. Part I. Adv Neurol Sci (Tokyo) 18:362–377

    Google Scholar 

  39. Tsuchida T (1974) A study of capillary ultrastructure of brain tumors in association with blood-brain barrier. Part II. Experimental mouse brain tumor. Adv Neurol Sci (Tokyo) 18: 595–602

    Google Scholar 

  40. Vick NA, Bigner DD (1972) Microvascular abnormalities in virally-induced brain tumors. Structural basis for altered blood-brain barrier function. J Neurol Sci 17:29–39

    Google Scholar 

  41. Vick NA, Bigner DD (1977) Chemotherapy of brain tumors. Arch Neurol 34:523–526

    Google Scholar 

  42. Waggener D, Beggs JL (1976) Vasculature of neural neoplasms. Adv Neurol 15:27–49

    Google Scholar 

  43. Warberg O (1956) The metabolism of tumors. Science 123:309–314

    Google Scholar 

  44. Weller RO, Foy M, Cox S (1977) The development and ultrastructure of the microvasculature in malignant gliomas. Neuropathol Appl Neurobiol 3:307–322

    Google Scholar 

  45. Westergaard E (1977) The blood-brain barrier to horseradish peroxidase under normal and experimental conditions. Acta Neuropathol (Berl) 39:181–187

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported in part by a grant for scientific research from the Japanese Ministry of Education (no. 56370026)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nishio, S., Ohta, M., Abe, M. et al. Microvascular abnormalities in ethylnitrosourea (ENU)-induced rat brain tumors: Structural basis for altered blood-brain barrier function. Acta Neuropathol 59, 1–10 (1983). https://doi.org/10.1007/BF00690311

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00690311

Key words

Navigation