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The effects of dexamethasone on experimental brain tumors: I. Transcapillary transport and blood flow in RG-2 rat gliomas

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Summary

Dexamethasone dramatically improves cerebral edema associated with malignant gliomas. Although the pathophysiology of this effect is not clearly understood, many investigators have postulated that tumor capillary permeability is reduced by dexamethasone. We studied blood-to-tissue transport and blood flow in 178 RG-2 transplanted gliomas in a control group and four groups given dexamethasone at doses of 3, 6, 9, and 12 mg/kg for four days.14C-α aminoisobutyric acid (AIB) was used to study blood-to-tissue transport in 31 animals; in an additional 27 animals14C-AIB and131I-iodoantipyrine (IAP) were used in double label experiments to study blood-to-tissue transport and blood flow. Regional measurements of the transfer constant (K) of AIB and blood flow (F) were made with quantitative autoradiography. There were significant differences between the control and dexamethasone-treated groups with regard to weight loss and plasma glucose. However, there wasno significant effect of dexamethasone on values of K or F, regardless of the tumor or brain region examined, and regardless of the dose of dexamethasone administered. Analysis of the profiles of the transfer constant of AIB in the brain around tumor showed that the K of AIB decreased within 0.5 mm of the tumor edge in direct relationship to the dexamethasone dose. These results do not support the hypothesis that dexamethasone reduces brain tumor capillary permeability, and suggest that dexamethasone may decrease tumor-associated cerebral edema by effects on bulk flow away from the tumor margin.

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References

  1. Reuien H-J, Hadjidimos A, Phase A: Steroids in the treatment of brain edema. In: Schurmann K, Brock M, Reuien H-J, Voth D (eds) Cerebello Pontine Angle Tumors: Diagnosis and Surgery. Springer-Verlag, Berlin, 1973, pp. 92–105

    Google Scholar 

  2. Luthert PJ, Greenwood J, Lantos PL, Pratt OE: The effect of dexamethasone on vascular permeability of experimental brain tumors. Acta Neuropathologica (Berl). 69: 288–294, 1986

    Google Scholar 

  3. Nakagawa H, Groothuis DR, Owens ES, Fenstermacher JD, Patlak CS, Blasberg RG: Dexamethasone effects on125I-albumin distribution in experimental RG-2 gliomas and adjacent brain. J Cerebral Blood Flow. Metab. 7: 687–701, 1987

    Google Scholar 

  4. Nakagawa H, Groothuis DR, Owens ES, Patlak CS, Blasberg RG: Dexamethasone effects on vascular volume and tissue hematocrit in experimental RG-2 gliomas and adjacent brain. J Neuro-Oncol 6: 157–168, 1988

    Google Scholar 

  5. Shapiro WR, Hiesiger EM, Cooney GA, Basler GA, Lipschultz LE, Posner JB: Temporal effects of dexamethasone on blood-to-brain and blood-to-tumor transport of14C-alpha-aminoisobutyric acid in rat C6 glioma. J Neuro-Oncol 8: 197–204, 1990

    Google Scholar 

  6. Yamada K, Bremer AM, West CR: Effects of dexamethasone on tumor-induced brain edema and its distribution in the brain of monkeys. J Neurosurg 50: 361–367, 1979

    PubMed  Google Scholar 

  7. Yamada K, Ushio Y, Hayakawa T, Arita N, Yamada N, Mogami H: Effects of methylprednisolone on peritumoral brain edema: a quantitative autoradiographic study. J Neurosurg 59: 612–619, 1983

    PubMed  Google Scholar 

  8. Brooks DJ, Beaney RP, Leenders KL: The effect of dexamethasone therapy on cerebral haemodynamics, oxygen utilization and blood-brain barrier permeability in patients with brain tumors. In: Capildeo R (ed): Steroids in Diseases of the Central Nervous System. John Wiley and Sons, New York, 1989, pp. 59–68

    Google Scholar 

  9. Jarden JO, Dhawan V, Poltorak A, J.B. P, Rottenberg DA: Positron emission tomographic measurement of blood-tobrain and blood-to-tumor transport of82Rb: the effect of dexamethasone and whole-brain radiation therapy. Ann Neurol 18: 636–646, 1985

    PubMed  Google Scholar 

  10. Jarden JO, Dhawan V, Moeller JR, Strother SC, Rottenberg DA: The time course of steroid action on blood-to-brain and blood-to-tumor transport of82Rb: a positron emission tomographic study. Ann Neurol 25: 239–245, 1989

    PubMed  Google Scholar 

  11. Leenders, KL, Beany DJ, Brooks DJ, Lammertsma JD, Heather JD, McKenzie CG: Dexamethasone treatment of brain tumor patients: Effects on regional cerebral blood flow, blood volume, and oxygen utilization. Neurol 35: 1610–1616, 1985

    Google Scholar 

  12. Groothuis DR, Fischer JM, Pasternak JF, Blasberg RG, Bigner DD, Vick NA: Regional measurements of blood-to-tissue transport in transplanted RG-2 rat gliomas. Cancer Res 43: 3368–3373, 1983

    PubMed  Google Scholar 

  13. Blasberg RG, Groothuis DR, Molnar P: The application of quantitative autoradiographic measurements in experimental brain tumors. Sem Neurol 1: 203–223, 1981

    Google Scholar 

  14. Molnar P, Blasberg RG, Groothuis DR, Bigner DD, Fenstermacher JD: Regional blood-to-tissue transport in avian sarcoma virus (ASV)-induced brain tumors. Neurol 33: 702–711, 1983

    Google Scholar 

  15. Blasberg RG, Groothuis DR, Molnar P: The application of quantitative autoradiographic measurements in experimental brain tumors. Sem Neurol 1: 203–221, 1981

    Google Scholar 

  16. Vriesendorp FJ, Groothuis DR, Vick NA: Murine sarcoma virus-induced brain tumors: concurrent measurements of blood flow and transcapillary transport. J Neuro-Oncol 2: 301–314, 1984

    Google Scholar 

  17. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin G, Sokoloff L: Measurement of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol 234: H59-H66, 1978

    PubMed  Google Scholar 

  18. Blasberg R, Patlak C, Fenstermacher J: The transport of alpha-aminoisobutyric acid across brain capillary and cellular membranes. J Cerebral Blood Flow Metab 3: 8–32, 1983

    Google Scholar 

  19. Ziylan YZ, Lefauconnier JM, Bernard G, Bourre JM: Regional alterations in blood-to-brain transfer of α-aminoisobutyric acid and sucrose, after chronic administration and withdrawal of dexamethasone. J Neurochem 52: 684–689 1989

    PubMed  Google Scholar 

  20. Ziylan YZ, LeFauconnier JM, Bernard G, Bourre JM: Effect of dexamethasone on transport of α-aminoisobutyric acid and sucrose across the blood brain barrier. J Neurochem 51: 1338–1342, 1988

    PubMed  Google Scholar 

  21. Warnke PC, Molnar PD, Lapin GD, Kuruvilla A, Groothuis R: The effects of dexamethasone on transcapillary transport in experimental brain tumors: II. Canine brain tumors. J Neuro-Oncol 25: 29–38, 1995

    Google Scholar 

  22. Benedek GB, Villars FMH: Physics With Illustrative Examples From Medicine and Biology. In Addison-Wesley Publ. Co. (ed): Addison-Wesley Publ. Co., Reading, MA, 1979

    Google Scholar 

  23. Fenstermacher JD, Blasberg RG, Patlak CS: Methods for quantifying the transport of drugs across brain barrier systems. Pharmacol Ther 14: 217–248, 1981

    PubMed  Google Scholar 

  24. Tajima A, Yen M-H, Nakata Het al.: Effects of dexamethasone on blood flow and volume of perfused microvessels in traumatic brain edema. In: Long DM (ed) Brain Edema: Pathogenesis, Imaging and Therapy. Raven Press, New York, 1990, pp 343–350

    Google Scholar 

  25. Yen M-H, Wright D, Nakagawa Het al: Effects of dexamethasone on the blood-brain distribution of [125I] albumin and [14C]alpha-aminoisobutyric acid in vasogenic cerebral edema. In: Inaba Y, Klatzo I, Spatz M (ed) Brain Edema. Springer Verlag, Berlin, 1985, pp. 638–645

    Google Scholar 

  26. Kristjansen PEG, Boucher Y, Jain RK: Dexamethasone reduces the interstitial pressure in a human colon adenocarcinoma xenograft. Cancer Res 53: 4764–4766, 1993

    PubMed  Google Scholar 

  27. Bothe H-W, Bodsch W, Hossmann K-A: Relationship between specific gravity, water content, and serum protein extravasation in various types of vasogenic brain edema. Acta Neuropathologica 64: 37–42, 1984

    PubMed  Google Scholar 

  28. Hossman K-A, Hurter T, Oschlies U: The effect of dexamethasone on serum protein extravasation and edema development in experimental brain tumors of cat. Acta Neuropathologica 60: 223–231, 1983

    PubMed  Google Scholar 

  29. Hassel B, Iversen EG, Fonnum F: Neurotoxicity of albuminin vivo. Neurosci Lett 167: 29–32, 1994

    PubMed  Google Scholar 

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Molnar, P., Lapin, G.D. & Groothuis, D.R. The effects of dexamethasone on experimental brain tumors: I. Transcapillary transport and blood flow in RG-2 rat gliomas. J Neuro-Oncol 25, 19–28 (1995). https://doi.org/10.1007/BF01054719

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