Radiobiological Effects of Photon Radiosurgery on Choroid Plexus Cells in Vitro

Abstract

The standard surgical treatment of hydrocephalus by cerebrospinal fluid (CSF) shunt is accompanied by numerous complications. The search for alternative treatment methods includes resection, coagulation and irradiation of part of the plexus choroideus. The reduction of CSF secretion after choroid plexus (CP) irradiation has been investigated only on the experimental level. The new Photon Radiosurgery System (PRS) now also provides clinically the opportunity to induce selective radionecrosis on the CP with high efficiency and safety. In order to achieve a basic understanding of the reaction of CP cells after PRS irradiation, we investigated the cell death after different irradiation doses using TB dye-exclusion and MTT assay on sheep choroid plexus (SCP) cells. We observed a dose-dependent decrease in cell survival with increasing doses of irradiation (9, 18, 27 and 36 Gy). Lower irradiation doses (9, 18 Gy) induced an initial decrease of cell survival. Cells were able to recover from day 6 on and achieved a similar cell viability compared to non-irradiated cells on day 12. In contrast, higher doses (27 and 36 Gy) of irradiation induced a constant decrease of the cell survival over 12 days. These results clearly demonstrate that PRS irradiation is able to induce radionecrosis of CP cells which are responsible for the secretion of CSF. Interstitial photon radiosurgery can provide the opportunity to deliver the irradiation dose locally to CP with minimal exposure of surrounding tissue. Our basic data support further studies investigating this concept in animal models and clinically.

Key words

Hydrocephalus - choroid plexus - experimental radiosurgery - photon radiosurgery system (PRS) - cell death

References

• 1 Sullivan H G, Allison J D. Physiology of Cerebrospinal Fluid. In: Wilkins RH, Rengachary SS (eds). Neurosurgery New York: McGraw-Hill 1985
• 2 Hirano A. A guide to Neuropathology. IGAKU-SHOIN 1981: 289-291
• 3 Sainte-Rose C. Hydrocephalus in Childhood. In: Youmans JR (ed). Neurological Surgery: A Comprehensive Reference Guide to the Diagnosis and Management of Neurosurgical Problems. Philadelphia: W. B. Saunders 1986
• 4 Dandy W E, Blackfan K D. Hydrocephalus internus. Eine experimentelle, klinische und pathologische Untersuchung.  Beitr Klein Chir. 1914;  93 392-484
• 5 Scarff J E. Nonobstructive hydrocephalus. Treatment by endoscopic cauterisation of the choroid plexus. Long term results.  J Neurosurg. 1952;  9 164-176
• 6 Pople I K, Ettles D. The role of endoscopic choroid plexus coagulation in the management of hydrocephalus.  Neurosurgery. 1995;  36 698-701
• 7 Calvo W, Hopewell J W, Reinhold H S, Yeung T K. Radiation induced damage in the choroid plexus of the rat brain: a histological evaluation.  Neuropathol Appl Neurobiol. 1986;  12 47-61
• 8 Weiss M H, Roessmann U. Radioactive tissue changes induced to control experimental hydrocephalus.  J Neurosurg. 1972;  36 266-269
• 9 Weiss M H, Nulsen F E, Kaufman . Selective radionecrosis of the choroid plexus for control of experimental hydrocephalus.  J Neurosurg. 1972;  36 270-275
• 10 Beatty J, Biggs P J, Gall K, Okunieff P, Pardos F S, Harte K J, Dalterio M J, Sliski A P. A new miniature x-ray device for interstitial radiosurgery: dosimetry.  Med Phys. 1996;  23 53-62
• 11 Dinsmore M, Harte K J, Sliski A P, Smith D O, Nomikos P M, Dalterio M J, Boom A J, Leonard W F, Oettinger P E, Yanch J C. A new miniature x-ray source for interstitial radiosurgery: device description.  Med Phys. 1996;  23 45-52
• 12 Cosgrove G R, Hochberg F H, Zervas N T, Pardos F S, Valenzuela R F, Chapman P. Interstitial irradiation of brain tumors, using a miniature radiosurgery device: initial experience.  Neurosurgery. 1997;  40 518-523
• 13 Price P, McMillan T J. The use of non-clonogenic assays in measuring the response of cells in vitro to ionising radiation.  Eur J Cancer. 1994;  30A 838-841
• 14 Lindl T. Zell- und Gewebekultur: Einführung in die Grundlagen sowie ausgewählte Methoden und Anwendungen. Heidelberg, Berlin: Spektrum Akad. Verlag 2000
• 15 Slavotinek A, McMillan T J, Steel C M. Measurement of radiation survival using the MTT assay.  Eur J Cancer. 1994;  30A 1376-1382
• 16 Gilbert H A, Kagen A R. Experimental Observations: Delayed Necrosis in Normal Monkey Brain. In: Caveness WF (ed). Radiation Damage to the Nervous System: A Delayed Therapeutic Hazard. New York: Raven Press 1980
• 17 Banasiak D, Barnetson A R, Odell R A, Mameghan H, Russel P J. Comparison between the clonogenic, MTT, and SRB assays for determining radiosensitivity in a panel of human bladder cancer cell lines and a ureteral cell line.  Radiat Onco Invest. 1999;  7 77-85
• 18 Oi S, Yamada H, Sato O, Matsumoto S. Experimental models of congenital hydrocephalus and comparable clinical problems in the fetal and neonatal periods.  Childs Nerv Syst. 1996;  12 292-302