Summary
With the aim of studying the putative involvement of peritumoral microvessels in the formation of brain edema, small pieces of peritumoral brain tissue were removed from six patients with glioblastoma multiforme submitted to surgery. All patients had cerebral edema, as shown by preoperative C.T. and N.M.R. Control specimens were obtained from four patients undergoing ventriculo-peritoneal shunt. The tissue fragments were fixed in glutaraldehyde-osmium and embedded in Epon. In semi-thin sections observed under light microscopy peritumoral endothelial cells exhibited voluminous cytoplasm and nucleus.
Under the electron microscope, capillary cells from glioblastoma patients differed from controls mainly by showing nuclei rich in euchromatin, cytoplasm rich in pinocytotic vesicles and with occasional fenestrations. All these morphological characteristics are compatible with a process of reversion of phenotype of capillaries around glioblastomas to that of periphery as well as an increase in permeability. Both events may be due to diffusion of a tumoral vascular permeability/endothelial growth factor. This peripheral vessel phenotype of peritumoral microvessels supports their participation in the formation of brain edema and may provide a new clue for therapeutic intervention: for example it fits quite well to the known increase in permeability by leukotrienes and decrease in permeability by corticosteroids in tumoral edema.
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References
Goldman E: Vitalfarbung am Zentralnervensystem. Beitrag zur Physiopathologie des Plexus Choroideus und der Hirnhaute. Abh Preuss Akad Wiss Phys-Math 1: 1–60, 1913
Geig NH: Brain tumors and the blood-brain barrier. In: Neuwelt EA (ed) Implications of the Blood-Brain Barrier and Its Manipulation, Vol 12, Plenum Medical Book Company, New York and London 77–106, 1989
Reese T, Karnovsky M: Fine ultrastructural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34: 207–217, 1967
Wahl M, Unterberg A, Baethmann A, Schilling L: Mediators of blood-brain barrier dysfunction and formation of vasogenic brain edema. J Cereb Blood Flow Metab 8: 621–634, 1988
Klatzo I: Neuropathological aspects of brain edema. J Ncuropathol Exp Neurol 26: 1–14, 1967
Cervós-Navarro J, Kannuki S, Nakagawa Y: Blood-brain barrier. Review from morphological aspect. Histol Histopathol 3: 203–213, 1988
Bruce J, Criscuolo GR, Merrill MJ: Vascular permeability induced by protein product of malignant brain tumors: inhibition by dexamethasone. J Neurosurg 67: 880–884, 1987
Criscuolo GR, Merrill MJ, Oldfield EH: Further characterization of malignant glioma-derived vascular permeability factor. J Neurosurg 69: 254–262, 1988
Quindlen EA, Bucher AP: Correlation of tumor plasminogen activator with peritumoral cerebral edema. J Neurosurg 66: 729–733, 1987
Robert AM, Godeau G, Miskulin M: Mechanism of action of collagenase on the permeability of the blood-brain barrier. Neurochem Res 2: 449–455, 1977
Senger DR, Galli SJ, Dvorak HE: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219: 983–985, 1983
Senger DR, Perruzzi CA, Feder J: A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res 46: 5629–5632, 1986
Ohnishi T, Sher PB, Posner JB, Shapiro WR: Capillary permeability factor secreted by malignant brain tumor. J Neurosurg 72: 245–251, 1990
Levin V, Freeman M, Landahl H: The permeability characteristics of brain adjacent to intracerebral rat tumors. Arch Neurol 32: 785–791, 1975
Long DM: Capillary ultrastructure and the blood-brain barrier in human malignant brain tumors. J Neurosurg 32: 127–144, 1970
Long DM: Capillary ultrastructure in human metastatic brain tumors. J Neurosurg 51: 53–58, 1979
Torack R: Ultrastructure of capillary reaction to brain tumors. Arch Neurol 5: 416–428, 1961
Gaetani P, Baena RR, Marzatico F, Lombardi D, Knerich R, Paoletti P: ‘Ex vivo’ release of eicosanoid from human brain tissue: its relevance in the development of brain edema. Neurosurg 28: 853–858, 1981
Hiesiger EM, Voorhies RM, Basler GA: Opening the bloodbrain and blood-tumor barriers in experimental rat brain tumors: the effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow. Ann Neurol 19: 50–59, 1986
Pappius HM: Dexamethasone and local cerebral glucose utilization in freeze-traumatized rat brain. Ann Neurol 12: 157–162, 1982
Yamada K, Ushio Y, Hayakawa T, Arita N, Yamada N, Mogami H: Effects of methylprednisolone on peritumoral brain edema. J Neurosurg 59: 612–619, 1983
Azevedo I, Castro-Tavares J, Garrett J: Ultrastructural changes in blood vessels of perinephritic hypertensive dogs. Blood Vessels 18: 110–119, 1981
Sarmento A, Soares-da-Silva P, Albino-Teixeira A, Azevedo I: Effects of denervation induced by 6-hydroxydopamine on cell nucleus activity of arterial and cardiac cells of the dog. J Auton Pharmacol 7: 119–126, 1987
Weibel ER: Stereological techniques for electron microscopic morphometry. In: Hayat MA (ed) Principles and Techniques of Electron Microscopy, Vol III, Van Nostrand Reinhold Company, New York, 1973
Constantinides P: Functional electronic histology. Elsevier Scientific Publishing Company, Amsterdam, 1974
Ghadially FN: Ultrastructural pathology of the cell. Butterworths, London, 1975
Branco D, Albino-Teixeira A, Azevedo I, Osswald W: Structural and functional alterations caused at the extraneuronal level by sympathetic denervation of blood vessels. Naunyn Schmiedeberg's Arch Pharmacol 326: 302–312, 1984
Connoly DT, Olander JV, Heuvelman D, Nelson R: Human vascular permeability factor. Isolation from U937 cells. J Biol Chem 264: 20017–20024, 1989
Whittle IR, Ironside JW, Piper IR, Miller JD: Neuropathological and neurophysiological effects of interstitial white matter autologous and non-autologous protein containing solutions: further evidence for a glioma derived permeability factor. Acta Neurochir (Wien) 120: 164–174, 1993
Keck PJ, Hauser SD, Krivi G, Sanzo K: Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246: 1309–1312, 1988
Kim KJ, Li B, Winder J, Armanini M, Gillett N, Phillips HS, Ferrara N: Inhibition of vascular endothelial growth factor-induced angiogenesis supresses tumor growth in vivo. Nature 362: 841–844, 1993
Brem S, Tsanaclis AMC, Gately S, Gross JL, Herblin WF: Immunolocalization of basic fibroblast growth factor to the microvasculature of human brain tumors. Cancer 70: 2673–2680, 1992
Li VW, Folkerth RD, Watanabe H, Yu C, Rupnick M, Barnes P, Scott RM, Black PMcL, Sallan SE, Folkman J: Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumors. Lancet 344: 82–86, 1994
Plate KH, Breier G, Weich HA, Risau W: Vascular endothelial growth factor is a potential tumor angiogenesis factor in human gliomas in vivo. Nature 359: 845–848, 1992
Baba T, Chio C-C, Black KL: The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in experimental brain tumors. J Neurosurg 77: 403–406, 1992
Black KL, Hoff JT, McGillicuddy JE, Gebarski SS: Increased leukotriene C4 and vasogenic edema surrounding brain tumors in humans. Ann Neurol 19: 592–595, 1986
Unterberg A, Schmidt W, Wahl M, Baethmann A: Role of leukotrienes as mediator compounds in brain edema. Adv Neurol 52: 211–214, 1990
Unterberg A, Schmidt W, Wahl M, Ellis EF, Marmarou A, Baethmann A: Evidence against leukotrienes as mediators of brain edema. J Neurosurg 74: 773–780, 1991
Feurstein G: Leukotrienes and the cardiovascular system. Prostaglandins 27: 781–802, 1984
Piper PJ: Formation and actions of leukotrienes. Physiol Rev 64: 744–761, 1984
Nelson SR, Dick AR: Steroids in the treatment of brain edema. In: Azarnoff DL (ed) Steroid Therapy, W.B. Saunders Co., Philadelphia 313–324, 1975
Haynes RC: Adrenocorticotropic hormone: adrenocortical steroids and their synthesis and actions of adrenocortical hormones. In: Goodman Gilman A, Rall TW, Nies AS, Taylor P (eds) Goodman and Gilman's The Pharmacological Basis of Therapeutics, Pergamon Press, New York 1431–1462, 1990
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Vaz, R., Borges, N., Sarmento, A. et al. Reversion of phenotype of endothelial cells in brain tissue around glioblastomas. J Neuro-Oncol 27, 127–132 (1996). https://doi.org/10.1007/BF00177475
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DOI: https://doi.org/10.1007/BF00177475