Possible Relationship between Vascular Permeability Factors, Endothelial Cells, and Peritumoral Brain Edema

A Neurosurgeon’s Perspective
  • Gregory Richard Criscuolo


Cerebral edema is a significant cause of the neurological morbidity associated with malignant brain tumors. Patients afflicted with intracranial neoplasms typically present with progressively worsening headaches, vomiting, blurred vision, double vision, and depressed level of consciousness. All of these clinical features are clearly related to elevated intracranial pressure (ICP), which may rapidly result in a patient’s demise if not treated promptly and effectively. The brain edema associated with cerebral tumors is an ultrafiltrate of plasma containing water, electrolytes, and plasma proteins, that emanates from the brain tumor microvasculature. Edema fluid typically infiltrates the white matter surrounding an intracerebral tumor in a diffuse manner, while relatively sparing the adjacent cortex. This excessive accumulation of cerebral interstitial tissue fluid contributes to the distortion of normal intracranial structures, and to elevation of the ICE As a result, cerebral edema is frequently as culpable for a brain tumor patient’s symptoms as the primary intracerebral neoplasm. It is now widely accepted that this excessive fluid accumulation results from a flaw in the integrity of the blood-brain barrier. The blood-brain barrier is both an anatomical and a physiological system which normally regulates the entry and egress of substances between the cerebral interstitial and intravascular compartments. The functional components of the blood-brain barrier occur primarily at the level of the vascular endothelial cell and, to a lesser extent, the basement membrane and astrocytic processes which invest the cerebral microvasculature.


Brain Tumor Brain Edema Cerebral Edema Cytosolic Calcium Malignant Brain Tumor 
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  1. 1.
    Ackerman, N. B., and Hechmer, P. A., 1978, Studies on the capillary permeability of experimental liver metastases, Surg. Gynecol. Obstet. 146:884–888.PubMedGoogle Scholar
  2. 2.
    Alessandri, G., Raju, K. S., and Gullino, P. M., 1986, Interaction of gangliosides with fibronectin in the mobilization of capillary endothelium. Possible influence on the growth of metastases, Invasion Metastasis 6:145–165.PubMedGoogle Scholar
  3. 3.
    Ammirati, M., Galicich, J. H., Arbit, E., and Liao, Y., 1987, Reoperation in the treatment of recurrent intracranial malignant gliomas, Neurosurgery 21:607–614.PubMedGoogle Scholar
  4. 4.
    Baethmann, A., 1978, Pathophysiological and pathochemical aspects of cerebral edema, Neurosurg. Rev. 1:85–100.Google Scholar
  5. 5.
    Betz, A. L., and Goldstein, G. W., 1980, Transport of hexoses, potassium and neutral amino acids into capillaries isolated from bovine retina, Exp. Eye Res. 30:593–605.PubMedGoogle Scholar
  6. 6.
    Black, K. L., and Hoff, J. T., 1985, Leukotrienes increase blood-brain barrier permeability following intraparenchymal injections in rats, Ann. Neurol. 18:349–351.PubMedGoogle Scholar
  7. 7.
    Blackwell, G. J., Canniccio, R., Di Rosa, M., Flower, R. J., Parente, L., and Persico, P., 1980, Macrocortin: A polypeptide causing the anti-phospholipase effect of glucocorticoids, Nature 287:147–149.PubMedGoogle Scholar
  8. 8.
    Bleehen, N. M., 1980, Intracranial tumors: Response and resistance to therapeutic endeavors, 1970–1980, Int. J. Radiat. Oncol. Biol. Phys. 8:1083–1133.Google Scholar
  9. 9.
    Bowman, P. D., Betz, A. L., and Goldstein, G. W., 1979, Characteristics of cultured brain capillaries, J. Cell Biol. 83:95a.Google Scholar
  10. 10.
    Bowman, P. D., Betz, A. L., Wolinsky, J. S., Penney, J. B., Shivers, R. R., and Goldstein, G. W., 1981, Primary culture of capillary endothelium from rat brain, In Vitro 17:353–362.PubMedGoogle Scholar
  11. 11.
    Brightman, M. W., and Reese, T. S., 1969, Junctions between intimately apposed cell membranes in the vertebrate brain, J. Cell Biol. 40:648–677.PubMedGoogle Scholar
  12. 12.
    Brightman, M. W., and Reese, T. S., 1970, Types of endothelium in normal and neoplastic brain tissue, 28th Annual Proceedings of the Electron Microscopic Society of America, pp. 98–99.Google Scholar
  13. 13.
    Brightman, M. W., Klatzo, I., Olsson, Y., and Reese, T. S., 1970, The blood-brain barrier to proteins under normal and pathological conditions, J. Neurol. Sci. 10:215–239.PubMedGoogle Scholar
  14. 14.
    Bruce, J. N., discuoio, G. R., Merrill, M. J., Moquin, R. R., Blacklock, J. B., and Oldfield, E. H., 1987, Vascular permeability induced by protein product of malignant brain tumors: Inhibition by dexamethasone, J. Neurosurg. 67:880–884.PubMedGoogle Scholar
  15. 15.
    Casanova, M. F., 1984, Vasogenic edema with intraparenchymal expanding mass lesions: A theory on its pathophysiology and mode of action of hyperventilation and corticosteroids, Med. Hypotheses 13:439–450.PubMedGoogle Scholar
  16. 16.
    Chan, P. H., and Fishman, R. A., 1984, The role of arachidonic acid in vasogenic brain edema, Fed. Proc. 43:210–213.PubMedGoogle Scholar
  17. 17.
    Connolly, D. T., Heuvelman, D. M., Nelson, R., Olander, J. V., Eppley, B. L., Delfino, J. J., Siegel, N. R., Leimgruber, R. M., and Feder, J., 1989, Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis, J. Clin. Invest. 84:1470–1478.PubMedGoogle Scholar
  18. 18.
    Criscuolo, G. R., Merrill, M. J., and Oldfield, E. H., 1988, Further characterization of malignant gliomaderived vascular permeability factor, J. Neurosurg. 69:254–262.PubMedGoogle Scholar
  19. 19.
    Criscuolo, G. R., Lelkes, P. I., Rotrosen, D., and Oldfield, E. H., 1989, Cytosolic calcium changes in endothelial cells induced by a protein product of human gliomas containing vascular permeability factor activity, J. Neurosurg. 71:884–891.PubMedGoogle Scholar
  20. 20.
    Cunha-Vaz, J. G., 1976, The blood-retinal barrier, Doc. Ophthalmol. 41:237–287.Google Scholar
  21. 21.
    Dempsey, R. J., Roy, M. W., Meyer, K., Tai, H. H., and Olson, J. W., 1985, Polyamine and prostaglandin markers in focal cerebral ischemia, Neurosurgery 17:635–640.PubMedGoogle Scholar
  22. 22.
    Drenckhahn, D., 1983, Cell motility and cytoplasmic filaments in vascular endothelium, Prog. Appl. Microcirc. 1:53–70.Google Scholar
  23. 23.
    Faden, A. I., Jacobs, T. P., Patrick, D. H., and Smith, M. T., 1984, Megadose corticosteroid therapy following experimental traumatic spinal injury, J. Neurosurg. 60:712–717.PubMedGoogle Scholar
  24. 24.
    Farrell, C. L., and Shivers, R. R., 1984, Capillary junctions of the rat are not affected by osmotic opening of the blood-brain barrier, Acta Neuropathol. 63:179–189.PubMedGoogle Scholar
  25. 25.
    Fishman, R. A., and Chan, P. H., 1981, Hypothesis: Membrane phospholipid degradation and polyunsaturated fatty acids play a key role in the pathogenesis of brain edema, Ann. Neurol. 10:75.Google Scholar
  26. 26.
    Folkman, J., Langer, R., Linhardt, R. J., Haudenschild, C., and Taylor, S., 1983, Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone, Science 221:719.PubMedGoogle Scholar
  27. 27.
    Folkman, J., and Klagsbrun, M., 1987, Angiogenic factors, Science 235:442–447.PubMedGoogle Scholar
  28. 28.
    Frankel, S. A., and Germans, W. J., 1958, Glioblastoma multiforme. Review of 219 cases with regard to natural history, pathology, diagnostic methods, and treatment, J. Neurosurg. 15:489–503.PubMedGoogle Scholar
  29. 29.
    Galicich, J. H., and French, L. A., 1961, Use of dexamethasone in the treatment of cerebral edema resulting from brain tumors and brain surgery, Am. Pract. 12:169–174.Google Scholar
  30. 30.
    Gerritsen, M. E., 1987, Eicosanoid production by the coronary microvascular endothelium, Fed. Proc. 46:47–53.PubMedGoogle Scholar
  31. 31.
    Gerritsen, M. E., Nganele, D. M., and Rodrigues, A. M., 1987, Calcium ionophore (A231887) and arachidonic acid-stimulated prostaglandin release from microvascular endothelial cells: Effects of calcium antagonists and calmodulin inhibitors, J. Pharmacol. Exp. Ther. 240:837–846.PubMedGoogle Scholar
  32. 32.
    Gimbrone, M. A., 1976, Culture of vascular endothelium, Prog. Hemostasis Thromb. 3:1–25.Google Scholar
  33. 33.
    Glick, R. P., Molteni, A., and Fors, E. M., 1983, Hormone binding in brain tumors, Neurosurgery 13: 513–519.PubMedGoogle Scholar
  34. 34.
    Goldsmith, M. A., and Carter, S. K., 1974, Glioblastoma multiforme—A review of therapy, Cancer Treat. Rev. 1:153–165.Google Scholar
  35. 35.
    Greenberg, D. A., 1987, Calcium channels and calcium channel antagonists, Ann. Neurol. 21:317–330.PubMedGoogle Scholar
  36. 36.
    Groothuis, D. R., and Vick, N. A., 1982, Brain tumors and the blood-brain barrier, Trends Neurosci. 5: 232–235.Google Scholar
  37. 37.
    Grynkiewicz, G., Poenie, M., and Tsien, R. Y., 1985, A new generation of Ca2+ indicators with greatly improved fluorescence properties, J. Biol. Chem. 260:3440–3450.PubMedGoogle Scholar
  38. 38.
    Gudeman, S. K., Miller, J. D., and Becker, D. P., 1979, Failure of high-dose steroid therapy to influence intracranial pressure in patients with severe head injury, J. Neurosurg. 51:301–306.PubMedGoogle Scholar
  39. 39.
    Hallam, T. J., and Pearson, J. D., 1986, Exogenous ATP raises cytoplasmic free calcium in fura-2 loaded piglet aortic endothelial cells, FEBS Lett. 207:95–99.PubMedGoogle Scholar
  40. 40.
    Harsh, G. R., Levin, V A., Gutin, P. H., Seager, M., Silver, P., and Wilson, C. B., 1987, Reoperation for glioblastoma and anaplastic astrocytoma, Neurosurgery 21:615–621.PubMedGoogle Scholar
  41. 41.
    Hoshi, H., and McKeehan, W. L., 1984, Brain- and liver cell-derived factors are required for growth of human endothelial cells in serum-free culture, Proc. Natl. Acad. Sci. USA 81:6413–6417.PubMedGoogle Scholar
  42. 42.
    Hossmann, K. A., Hurter, T., and Oschlies, U., 1983, The effect of dexamethasone on serum protein extravasation and edema development in experimental brain tumors of cat, Acta Neuropathol. 60:223–231.PubMedGoogle Scholar
  43. 43.
    Ikeda, Y., Anderson, J. H., and Long, D. M., 1989, Oxygen free radicals in the genesis of traumatic and peritumoral brain edema, Neurosurgery 24:679–685.PubMedGoogle Scholar
  44. 44.
    Ikeda, Y., Ikeda, K., and Long, D. M., 1989, Comparative study of different iron-chelating agents in cold-induced brain edema, Neurosurgery 24:820–824.PubMedGoogle Scholar
  45. 45.
    Jaffe, E. A., Nachman, R. L., Becker, C. G., and Minick, C. R., 1973, Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria, J. Clin. Invest. 52:2745–2756.PubMedGoogle Scholar
  46. 46.
    Jaffe, E. A., 1977, Endothelial cells and the biology of factor VIII, N. Engl. J. Med. 296:377–383.PubMedGoogle Scholar
  47. 47.
    Keck, P. J., Hauser, S. D., Krivi, G., Sanzo, K., Warren, T., Feder, J., and Connolly, D. T., 1989, Vascular permeability factor, an endothelial cell mitogen related to PDGF, Science 246:1309–1312.PubMedGoogle Scholar
  48. 48.
    Klatzo, I., 1967, Presidential address. Neuropathological aspects of brain edema, J. Neuropathol. Exp. Neurol. 26:1–14.PubMedGoogle Scholar
  49. 49.
    Kornblum, J. A., Bay, J. W., and Gupta, M. K., 1988, Steroid receptors in human brain and spinal cord tumors, Neurosurgery 23:185–188.PubMedGoogle Scholar
  50. 50.
    Leung, D. W., Cachianes, G., Kuang, W. J., Goeddel, D. V., and Ferrara, N., 1989, Vascular endothelial growth factor is a secreted angiogenic mitogen, Science 246:1306–1309.PubMedGoogle Scholar
  51. 51.
    Levin, V. A., 1981, Chemotherapy of recurrent brain tumors, in: Nitrosoureas (A. W. Prestayko, ed.), Academic Press, New York, pp. 259–268.Google Scholar
  52. 52.
    Liddell, R. H. A., Scott, A. R. W., and Simpson, G. J., 1981, Histamine-induced changes in the endothelium of post-capillary venules: Effects of chelating agents and cytochalasin B, Bibl. Anat. 20:109–112.Google Scholar
  53. 53.
    Lobb, R. R., Key, M. E., Alderman, E. M., and Fett, J. W., 1985, Partial purification and characterization of a vascular permeability factor secreted by a human colon adenocarcinoma line, Int. J. Cancer 36:473–478.PubMedGoogle Scholar
  54. 54.
    Long, D. M., Hartmann, J. F., and French, L. A., 1966, The response of human cerebral edema to glucosteroid administration. An electron microscopic study, Neurology 16:521–528.PubMedGoogle Scholar
  55. 55.
    Long, D. M., 1970, Capillary ultrastructure and the blood-brain barrier in human malignant brain tumors, J. Neurosurg. 32:127–144.PubMedGoogle Scholar
  56. 56.
    Long, D. M., 1973, Vascular ultrastructure in human meningiomas and schwannomas, J. Neurosurg. 38:409–419.PubMedGoogle Scholar
  57. 57.
    Long, D. M., 1979, Capillary ultrastructure in human metastatic brain tumors, J. Neurosurg. 51:53–58.PubMedGoogle Scholar
  58. 58.
    Majno, G., and Palade, G. E., 1961, Studies on inflammation I. Effect of histamine and serotonin on vascular permeability: An electron microscopic study, J. Biophys. Biochem. Cytol. 11:571–605.PubMedGoogle Scholar
  59. 59.
    Majno, G., Gilmore, V., and Leventhal, M., 1967, On the mechanism of vascular leakage caused by histamine-type mediators, Circ. Res. 21:833–847.PubMedGoogle Scholar
  60. 60.
    Malgaroli, A., Milani, D., Meldolesi, J., and Pozzan, T., 1987, Fura-2 measurement of cytosolic free Ca2+ in monolayers and suspensions of various types of animal cells, J. Cell Biol. 105:2145–2155.PubMedGoogle Scholar
  61. 61.
    Meezan, E., Brendel, K., and Carlson, E. C., 1974, Isolation of a purified preparation of metabolically active retinal blood vessels, Nature 251:65–67.PubMedGoogle Scholar
  62. 62.
    Miles, A. A., and Miles, E. M., 1952, Vascular reactions to histamine, histamine liberator and leukotaxine in the skin of guinea pigs, J. Physiol. (London) 118:228–257.Google Scholar
  63. 63.
    Northover, A. M., and Northover, B. J., 1987, Changes in vascular endothelial shape and of membrane potential in response to the ionophore A23187, Int. J. Microcirc. Clin. Exp. 6:137–148.PubMedGoogle Scholar
  64. 64.
    Oldendorf, W. H., Cornford, M. E., and Brown, W. J., 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. 5:409–417.Google Scholar
  65. 65.
    Owen, D. A. A., Poy, E., Woodward, D. F., and Daniel, D., 1980, Evaluation of the role of histamine H1 and H2 receptors in cutaneous inflammation in the guinea pig produced by histamine and mast cell degranulation, Br. J. Pharmacol. 69:615–623.PubMedGoogle Scholar
  66. 66.
    Phillipon, J., Foncin, J. F., Grob, R., Srour, A., Poisson, M., and Pertuiset, B. F., 1984, Cerebral edema associated with meningiomas: Possible role of a secretory-excretory phenomenon, Neurosurgery 14: 295–301.Google Scholar
  67. 67.
    Poungvarin, N., Bhoopat, W., Viriyavejakul, A., Rodprasert, P., Buranasiri, P., Sukondhabhant, S., Hensley, M. J., and Strom, B. L., 1987, Effects of dexamethasone in primary supratentorial intracerebral hemorrhage, N. Engl. J. Med. 316:1229–1233.PubMedGoogle Scholar
  68. 68.
    Quindlen, E. A., and Bucher, A. P., 1987, Correlation of tumor plasminogen activator with peritumoral cerebral edema: A CT and biochemical study, J. Neurosurg. 66:729–733.PubMedGoogle Scholar
  69. 69.
    Reichman, H. R., Farrell, C. L., and Del Maestro, R. F., 1986, Effects of steroids and nonsteroid antiinflammatory agents on vascular permeability in a rat glioma model, J. Neurosurg. 65:233–237.PubMedGoogle Scholar
  70. 70.
    Reulen, H. J., 1976, Vasogenic brain edema. New aspects in its formation, resolution and therapy, Br. J. Anaesth. 48:741–752.PubMedGoogle Scholar
  71. 71.
    Roblin, R., and Young, P. L., 1980, Dexamethasone regulation of plasminogen activator in embryonic and tumor-derived human cells, Cancer Res. 40:2706–2713.PubMedGoogle Scholar
  72. 72.
    Rotrosen, D., and Gallin, J. I., 1986, Histamine type I receptor occupancy increases endothelial cytosolic calcium, reduces F-actin, and promotes albumin diffusion across cultured endothelial monolayers, J. Cell Biol. 103:2379–2387.PubMedGoogle Scholar
  73. 73.
    Rutherford, R. B., and Ross, R., 1976, Platelet factors stimulate fibroblasts and smooth muscle cells quiescent in plasma serum to proliferate, J. Cell Biol. 69:196–203.PubMedGoogle Scholar
  74. 74.
    Ryan, U. S., Clements, E., Habliston, D., and Ryan, J. W., 1978, Isolation and culture of pulmonary artery endothelial cells, Tissue Cell 10:535–554.PubMedGoogle Scholar
  75. 75.
    Ryan, U. S., Mortara, M., and Whitaker, C., 1980, Method of microcarrier culture of bovine pulmonary artery endothelial cells avoiding the use of enzymes, Tissue Cell 12:619–635.PubMedGoogle Scholar
  76. 76.
    Schook, L. B., Otz, U., Lazary, S., De Weck, A. L., Minowadr, J., Odavic, R., Kniep, E. M., and Edy, V., 1981, Lymphokine and monokine activities in supernatants from human lymphoid and myeloid cell lines, Lymphokines 2:1–19.Google Scholar
  77. 77.
    Seiler, N., Knodgen, B., and Bartholeyns, J., 1985, Polyamine metabolism and polyamine excretion in normal and tumor bearing rodents, Anticancer Res. 5:371–378.PubMedGoogle Scholar
  78. 78.
    Senger, D. R., Galli, S. I., Dvorak, A. M., Perruzzi, C. A., Harvey, V. S., and Dvorak, H. F., 1983, Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid, Science 219: 983–985.PubMedGoogle Scholar
  79. 79.
    Senger, D. R., Perruzzi, C. A., Feder, J., and Dvorak, H. F., 1986, A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines, Cancer Res. 46:5629–5632.PubMedGoogle Scholar
  80. 80.
    Senger, D. R., Connolly, D. T., Van De Water, L., Feder, J., and Dvorak, H. F., 1990, Tumor-secreted vascular permeability factor: Purification and N-terminal amino acid sequence, Cancer Res. 50:1774–1778.PubMedGoogle Scholar
  81. 81.
    Shapiro, W. R., and Byrne, T.N., 1983, Chemotherapy of brain tumors. Basic concepts in oncology of the nervous system, (M. D. Walker, ed.), Nijhoff, The Hague, pp. 65–100.Google Scholar
  82. 82.
    Shasby, D. M., Shasby, S. S., Sullivan, R., and Peach, M. J., 1982, Role of endothelial cell cytoskeleton in control of endothelial permeability, Circ. Res. 51:657–661.PubMedGoogle Scholar
  83. 83.
    Sheline, G. E., 1977, Radiation therapy of brain tumors, Cancer 39:873–881.PubMedGoogle Scholar
  84. 84.
    Shing, Y., Folkman, J., Sullivan, R., Butterfield, C., Murray, J., and Klagsbrun, M., 1984, Heparin affinity: Purification of a tumor-derived capillary endothelial cell growth factor, Science 223:1296–1299.PubMedGoogle Scholar
  85. 85.
    Simionescu, M., Simionescu, N., and Palade, G. E., 1975, Structural basis of permeability in sequential segments of the microvasculature of the diaphragm. II. Pathways followed by microperoxidase across the endothelium, Microvasc. Res. 15:17–36.Google Scholar
  86. 86.
    Stein-Werblowsky, R., 1980, A permeability-enhancing factor produced by tumor. The genesis of malignant effusions, J. Cancer Res. Clin. Oncol. 97:315–320.PubMedGoogle Scholar
  87. 87.
    Strausbaugh, L. J., 1987, Intracarotid infusions of protamine sulfate disrupt the blood-brain barrier of rabbits, Brain Res. 409:221–226.PubMedGoogle Scholar
  88. 88.
    Taylor, S., and Folkman, J., 1982, Protamine is an inhibitor of angiogenesis. Nature (London) 297:307.Google Scholar
  89. 89.
    Thomas, G., 1982, Mechanism of ionophore A23187 induction of plasma leakage and its inhibition by indomethacin, Eur. J. Pharmacol. 81:35–42.PubMedGoogle Scholar
  90. 90.
    Tosaki, A., Koltai, M., Joo, F., Adam, G., Szerdahelyi, P., Lepran, I., Takats, I., Szekeres, L., 1985, Actinomycin D suppresses the protective effect of dexamethasone in rats affected by global cerebral ischemia, Stroke 16:501–505.PubMedGoogle Scholar
  91. 91.
    Tucker, W. S., Kirsch, W. M., Martinez-Hernandez, A., and Fink, L. M., 1978, In vitro plasminogen activator activity in human brain tumors, Cancer Res. 38:297–302.PubMedGoogle Scholar
  92. 92.
    Tsien, R. Y., Rink, T. J., and Poenie, M., 1985, Measurement of cytosolic free Ca2+ in individual small cells using fluorescence microscopy with dual excitation wavelengths, Cell Calcium 6:145–157.PubMedGoogle Scholar
  93. 93.
    Ueki, H., Tsunemi, S., and Kubota, Y., 1975, Vascular permeability-increasing action of hypoalbuminemic substance from Ehrlich ascites carcinoma cells, Gann 66:237–243.PubMedGoogle Scholar
  94. 94.
    Underwood, J. C. E., and Carr, I., 1972, The ultrastructure and permeability characteristics of the blood vessels of a transplantable rat sarcoma, J. Pathol. 107:157–166.PubMedGoogle Scholar
  95. 95.
    Unterberg, A., and Baethmann, A. J., 1984, The kallikrein-kinin system as a mediator of vasogenic brain edema. Part 1: Cerebral exposure to bradykinin and plasma, J. Neurosurg. 61:87–96.PubMedGoogle Scholar
  96. 96.
    Vassalli, J. D., Hamilton, J., and Reich, E., 1976, Macrophage plasminogen activator: Modulation of enzyme production by anti-inflammatory steroids, mitotic inhibitors and cyclic nucleotides, Cell 8:271–281.PubMedGoogle Scholar
  97. 97.
    Vehaskari, V. M., Root, E. R., Germuth, F. G., and Robson, A. M., 1982, Glomerular charge and urinary protein excretion: Effects of systemic and intrarenal polycation infusion in the rat, Kidney Int. 22:127–135.PubMedGoogle Scholar
  98. 98.
    Vehaskari, V. M., Chang, C. T. C., Stevens, J. K., and Robson, A. M., 1984, The effects of polycations on vascular permeability in the rat, J. Clin. Invest. 73:1053–1061.PubMedGoogle Scholar
  99. 99.
    Voyta, J. C., Via, D. P., Butterfield, C. E., and Zetter, B. R., 1984, Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein, J. Cell Biol. 99:2034–2040.PubMedGoogle Scholar
  100. 100.
    Walker, M., Alexander, E., Hunt, W., MacCarty, C., Mahaley, M. S., Mealy, J., Norrell, H., Owens, G., Ransohoff, J., Wilson, C. B., Gehan, E., and Strike, T., 1978, Evaluation of BCNU and or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial, J. Neurosurg. 49:333–343.PubMedGoogle Scholar
  101. 101.
    Wall, R. T., Harker, L. A., Quadracci, L. J., and Striker, G. E., 1978, Factors influencing endothelial cell proliferation, J. Cell. Physiol. 96:203–214.PubMedGoogle Scholar
  102. 102.
    Ward, J. D., Hadfield, M. G., Becker, D. P., and Lovings, E. T., 1974, Endothelial fenestrations and other vascular alterations in primary melanoma of the central nervous system, Cancer 34:1982–1991.PubMedGoogle Scholar
  103. 103.
    Weibel, E. R., and Palade, G. E., 1964, New cytoplasmic components in arterial endothelia, J. Cell Biol. 23:101–112.PubMedGoogle Scholar
  104. 104.
    Yamada, K., Bremer, A. M., and West, C. R., 1979, Effects of dexamethasone on tumor-induced brain edema and its distribution in the brain of monkeys, J. Neurosurg. 50:361–367.PubMedGoogle Scholar
  105. 105.
    Yamada, K., Ushio, Y., Hayakawa, T., Kato, A., Yamada, N., and Mogami, H., 1982, Quantitative autoradiographic measurements of blood-brain barrier permeability in the rat glioma model, J. Neurosurg. 57:394–398.PubMedGoogle Scholar
  106. 106.
    Yu, Z. Y., Wrange, O., Boethius, J., Hatam, A., Granholm, L., and Gustafsson, J. A., 1981, A study of glucocorticoid receptors in intracranial tumors, J. Neurosurg. 55:575–760.Google Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Gregory Richard Criscuolo
    • 1
  1. 1.Division of of NeurosurgeryYale University School of MedicineNew HavenUSA

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