Neurosurgical Review

, Volume 27, Issue 2, pp 121–127 | Cite as

Effects of ionizing radiation on brain tissue surrounding arteriovenous malformations: an experimental study in a rat caroticojugular fistula model

  • Melike Mut
  • Kamil Öge
  • Faruk Zorlu
  • Ülkü Ündeğer
  • Sevim Erdem
  • Osman Ekin Özcan
Basic Research


Arteriovenous malformation (AVM) may change the cerebral hemodynamics. The purpose of this study was to detect the effects of ionizing radiation (IR) on tissues surrounding AVM in a rat caroticojugular fistula model. Forty rats were divided into four groups. Eight weeks after caroticojugular fistulas and chronic hypoperfusion were created in groups 1 and 2, IR was administered to groups 1 and 3. Group 4 was the control. Brain tissue samples were taken 72 h after irradiation. Comet assay to detect DNA strand breaks (DSB), terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay for apoptosis, and free radical measurement were performed. Although the difference between fistula plus irradiation (group 1) and fistula (group 2) was statistically insignificant in terms of DSB and free radical measurement, apoptotic cell count was significantly higher in group 1. Nonetheless, apoptotic cell count corresponded well with both free radicals and DSB in the irradiated group (group 3). Ionizing radiation resulted in significant apoptosis in both groups with or without fistulas. Chronic hypoperfusion might not prevent cerebral damage after IR. Optimal care should be taken with brain tissue around AVM during radiotherapy, regardless of presence or absence of the “steal” phenomenon.


Apoptosis Arteriovenous malformation Chronic hypoperfusion Comet assay Free radicals Ionizing radiation effect Rat model 



This study was supported by a grant from Hacettepe University School of Medicine. The authors would like to thank Prof. Dr. Kamer Kilinc for free radical measurements, Prof. Dr. Ersin Tan and Nursen Basaran, PhD for providing their laboratories, Ilker Etikan, PhD for statistical analysis, Bulent Cakir, Bulent Yapici, and Salih Gurdalli for their excellent technical assistance, and Lisa Foster for her editing of the manuscript.


  1. 1.
    Frankenberg-Schwager M (1990) Induction, repair and biological relevance of radiation-induced DNA lesions in eukaryotic cells. Radiat Environ Biophys 29:273–292PubMedGoogle Scholar
  2. 2.
    Lunec J (1990) Free radicals: their involvement in disease processes. Ann Clin Biochem 27:173–182PubMedGoogle Scholar
  3. 3.
    O’Neill P, Fielden EM (1993) Primary free radical processes in DNA. Adv Radiat Biol 17:53–120Google Scholar
  4. 4.
    Morgan MK, Anderson RE, Sundt TM Jr (1989) A model of the pathophysiology of cerebral arteriovenous malformations by a carotid-jugular fistula in the rat. Brain Res 496:241–250CrossRefPubMedGoogle Scholar
  5. 5.
    Morgan MK, Anderson RE, Sundt TM Jr (1989) The effects of hyperventilation on cerebral blood flow in the rat with an open and closed carotid-jugular fistula. Neurosurgery 25:606–612PubMedGoogle Scholar
  6. 6.
    Irikura K, Morii S, Miyasaka Y, Yamada M, Tokiwa K, Yada K (1996) Impaired autoregulation in an experimental model of chronic cerebral hypoperfusion in rats. Stroke 27:1399–1404PubMedGoogle Scholar
  7. 7.
    Sekhon LHS, Morgan MK, Spence I, Weber NC (1997) Chronic cerebral hypoperfusion: pathological and behavioral consequences experimental study. Neurosurgery 40:548–556PubMedGoogle Scholar
  8. 8.
    Flickinger JC, Pollock BE, Kondziolka D, Lunsford LD (1996) A dose-response analysis of arteriovenous malformation obliteration after radiosurgery. Int J Radiat Oncol Biol Phys 36:873–879CrossRefPubMedGoogle Scholar
  9. 9.
    Singh NP, McCoy MT, Tice RR, Schneider AA (1988) Simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191PubMedGoogle Scholar
  10. 10.
    Anderson D, Yu TW, Phillips BJ, Schmezer P (1994) The effects of various antioxidants and other modifying agents on oxygen-radical generated DNA damage in human lymphocytes in the COMET assay. Mutat Res 307:261–271PubMedGoogle Scholar
  11. 11.
    Sgonc R, Boeck G, Dietrich H, Gruber J, Recheis H, Wick G (1994) Simultaneous determination of cell surface antigens and apoptosis. Trends Genet 10:41–42PubMedGoogle Scholar
  12. 12.
    Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431PubMedGoogle Scholar
  13. 13.
    Batjer HH, Devous GB Sr, Seibert B, Purdy PD, Ajmani AK, Delarosa M, Bonte FJ (1988) Intracranial arteriovenous malformation: relationships between clinical and radiographic factors and ipsilateral steal severity. Neurosurgery 23:322–328PubMedGoogle Scholar
  14. 14.
    Bennett SA, Tenniswood M, Chen JH, Davidson CM, Keyes MT, Fortin T, Pappas BA (1998) Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment. Neuroreport 9:161–166PubMedGoogle Scholar
  15. 15.
    Jin K, Chen J, Nagayama T, Chen M, Sinclair J, Graham SH, Simon RP (1999) In situ detection of neuronal DNA strand breaks using the Klenow fragment of DNA polymerase I reveals different mechanisms of neuron death after global cerebral ischemia. J Neurochem 72:1204–1214CrossRefPubMedGoogle Scholar
  16. 16.
    Fairbairn DW, Olive PL, O’Neill KL (1995) The comet assay: a comprehensive review. Mutat Res 339:37–59PubMedGoogle Scholar
  17. 17.
    Olive PL (1998) The role of DNA single- and double-strand breaks in cell killing by ionizing radiation. Radiat Res 150 [Suppl]:S42–S51Google Scholar
  18. 18.
    Chapman JD, Reuvers AP, Borsa J, Greenstock CL (1973) Chemical radioprotection and radiosensitization of mammalian cells growing in vitro. Radiat Res 56:291–306PubMedGoogle Scholar
  19. 19.
    Greenstock CL (1984) Free-radical processes in radiation and chemical carcinogenesis. Adv Radiobiol 11:269–293Google Scholar
  20. 20.
    Skov KA (1984) The contribution of hydroxyl radical to radiosensitization: a study of DNA damage. Radiat Res 99:502–510PubMedGoogle Scholar
  21. 21.
    Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81–128PubMedGoogle Scholar
  22. 22.
    Harms-Ringdahl M, Nicotera P, Radford IR (1996) Radiation induced apoptosis. Mutat Res 366:171–179PubMedGoogle Scholar
  23. 23.
    Nornes H, Grip A (1980) Hemodynamic aspects of cerebral arteriovenous malformations. J Neurosurg 53:456–464PubMedGoogle Scholar
  24. 24.
    Feindel W, Perot P (1965) Red cerebral veins. A report on arteriovenous shunts in tumors and cerebral scars. J Neurosurg 22:315–325PubMedGoogle Scholar
  25. 25.
    Feindel W, Yamamoto L, Hodge CP (1971) Red cerebral veins and the cerebral steal syndrome. J Neurosurg 35:167–176PubMedGoogle Scholar
  26. 26.
    Altschuler E, Lunsford D, Kondziolka D, Wu A, Maitz AH, Sclabassi R, Martinez AJ, Flickinger JC (1992) Radiobiologic models for radiosurgery. Neurosurg Clin North Am 3:61–77Google Scholar
  27. 27.
    Szumiel I (1994) Ionizing radiation-induced cell death. Int J Radiat Biol 66:329–341PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Melike Mut
    • 1
    • 2
  • Kamil Öge
    • 3
  • Faruk Zorlu
    • 4
  • Ülkü Ündeğer
    • 5
  • Sevim Erdem
    • 6
  • Osman Ekin Özcan
    • 1
  1. 1.Department of NeurosurgeryHacettepe University School of MedicineAnkara Turkey
  2. 2.Department of NeurosurgeryUniversity of VirginiaCharlottesvilleUSA
  3. 3.Division of NeurosurgeryFatih UniversityAnkaraTurkey
  4. 4.Department of Radiation OncologyHacettepe University School of MedicineAnkaraTurkey
  5. 5.Department of Pharmaceutical Toxicology, Faculty of PharmacyHacettepe UniversityAnkaraTurkey
  6. 6.Department of NeurologyHacettepe University School of MedicineAnkaraTurkey

Personalised recommendations