Vplyv frakcionovaného ožiarenia na hipokampus v experimentálnom modeli

English version

Autoři: S. Bálentová ¹; E. Hajtmanová ²; B. Filova ³; V. Borbelyova ⁴; J. Lehotský ⁵
Působiště autorů: Institute of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovak Republic ¹; Department of Radiotherapy and Oncology, Martin University Hospital, Martin, Slovak Republic ²; Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University in Bratislava, Slovak Republic ³; Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University in Bratislava, Slovak Republic ⁴; Institute of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovak Republic ⁵
Vyšlo v časopise: Klin Onkol 2015; 28(3): 191-199
Kategorie: Původní práce
doi: https://doi.org/10.14735/amko2015191

Souhrn

Východiska:
Ionizujúce žiarenie ovplyvňuje tkanivovú homeostázu a môže viesť k jeho morfologickému a funkčnému poškodeniu. Cieľom štúdie bolo skúmať krátkodobé a dlhodobé účinky ionizujúceho žiarenia na populáciu buniek osidľujúcu hipokampus dospelého potkana.

Materiál a metódy:
Dospelým samcom potkanov kmeňa Wistar sme ožiarili cranium frakcionovanou dávkou gama žiarenia (celková dávka bola 20 Gy) a vyšetrovali 30 a 100 dní po expozícii. Pomocou histochemickej metodiky Fluoro-Jade C na dôkaz degenerujúcich neurónov, imunohistochemického farbenia na detekciu astrocytov a konfokálnej mikroskopie sme kvantitatívne hodnotili neurodegeneratívne zmeny v gyrus dentatus a oblasti CA1 hipokampu.

Výsledky:
V obidvoch vyšetrovaných oblastiach sme zistili signifikantný nárast počtu Fluoro-Jade C značených neurónov, predovšetkým v skupine prežívajúcej 30 dní po ožiarení. Počet GFAP-imunoreaktívnych astrocytov sa počas celého experimentu znížil len nepatrne.

Záver:
Naše súčasné výsledky poukazujú na to, že postradiačná odpoveď populácie buniek, ktorá tvorí hipokampus môže zohrávať úlohu vo vývoji neskorých postradiačných prejavov, ktoré sú z hľadiska prognózy veľmi nepriaznivé.

Kľúčové slová:
ionizujúce žiarenie – dávka žiarenia – potkan – hipokampus – Fluoro-Jade C – GFAP

Práca bola financovaná z projektu Centrum translačnej medicíny/Vytvorenie nového diagnostického algoritmu pri vybraných nádorových ochoreniach, ITMS: 26220220021 spolufinancovanými zo zdrojov EÚ a Európskeho fondu regionálneho rozvoja.

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.

Obdržané:
8. 3. 2015

Prijaté:
5. 4. 2015

Zdroje

1. Kempermann G. Why new neurons? Possible functions for adult hippocampal neurogenesis. J Neurosci 2002; 22(3): 635– 638.

2. Cicciarello R, d‘Avella D, Gagliardi ME et al. Time-related ultrastructural changes in an experimental model of whole brain irradiation. Neurosurgery 1996; 38(4): 772– 779.

3. Gaber MW, Sabek OM, Fukatsu K et al. The differences in ICAM-1 and TNF-α expression between high single fractions and fractionated irradiation in mouse brain. Int J Radiat Biol 2003; 79(5): 359– 366.

4. Yuan H, Gaber MW, Boyd K et al. Effects of fractionated radiation on the brain vasculature in a murine model: blood- brain barrier permeability, astrocyte proliferation, and ultrastructural changes. Int J Radiat Oncol Biol Phys 2006; 66(3): 860– 866.

5. Rosi S, Andres- Mach M, Fishman KM et al. Cranial irradiation alters the behaviorally induced immediate- early gene arc (activity- regulated cytoskeleton-associated protein). Cancer Res 2008; 68(23): 9763– 9770. doi: 10.1158/ 0008- 5472.CAN- 08- 1861.

6. Wilson CM, Gaber MW, Sabek OM et al. Radiation-induced astrogliosis and blood- brain barrier damage can be abrogated using anti-TNF treatment. Int J Radiat Oncol Biol Phys 2009; 74(3): 934– 941. doi: 10.1016/ j.ijrobp.2009.02.035.

7. Machida M, Lonart G, Britten RA. Low (60cGy) doses of (56)Fe HZE- particle radiation lead to a persistent reduction in the glutamatergic readily releasable pool in rat hippocampal synaptosomes. Radiat Res 2010; 174(5): 618– 623. doi: 10.1667/ RR1988.1.

8. Zhou H, Liu Z, Liu J et al. Fractionated radiation-induced acute encephalopathy in a young rat model: cognitive dysfunction and histologic findings. AJNR Am J Neuroradiol 2011; 32(10): 1795– 1800. doi: 10.3174/ ajnr.A2643.

9. Wong CS, Van der Kogel AJ. Mechanisms of radiation injury to the central nervous system: implications for neuroprotection. Mol Interv 2004; 4(5): 273– 284.

10. Taupin P. The Hippocampus. In: Taupin P (ed.). The Hip-pocampus: neurotransmission and plasticity in the nervous system. New York: Nova Science Publishers Inc 2007: 3– 6.

11. Schmued LC, Albertson C, Slikker W Jr. Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res 1997; 751(1): 37– 46.

12. Schmued LC, Hopkins KJ. Fluoro-Jade: novel fluorochromes for detecting toxicant-induced neuronal degeneration. Toxicol Pathol 2000; 28(1): 91– 99.

13. Ballok DA, Millward JM, Sakic B. Neurodegeneration in autoimmune MRL- lpr mice as revealed by Fluoro Jade B staining. Brain Res 2003; 964(2): 200– 210.

14. Balentova S, Hajtmanova E, Kinclova I et al. Long-term alterations of cell population in the adult rat forebrain following exposure to fractionated doses of ionizing radiation. Gen Physiol Biophys 2013; 32(1): 91– 100. doi: 10.4149/ gpb_2013009.

15. Peissner W, Kocher M, Treuer H et al. Ionizing radiation-induced apoptosis of proliferating stem cells in the dentate gyrus of the adult rat hippocampus. Mol Brain Res 1999; 71(1): 61– 68.

16. Tada E, Yang C, Gobbel GT. Long-term impairment of subependymal repopulation following damage by ionizing radiation. Exp Neurol 1999; 160(1): 66– 77.

17. Mizumatsu S, Monje LM, Morhardt DR et al. Extreme sensitivity of adult neurogenesis to low doses of X- irradiation. Cancer Res 2003; 63(14): 4021– 4027.

18. Raber J, Rola R, Lefevour A et al. Radiation induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Rad Res 2004; 162(1): 39– 47.

19. Rola R, Raber J, Rizk A et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol 2004; 188(2): 316– 330.

20. Fan Y, Liu Z, Weinstein PR et al. Enviromental enrichment enhances neurogenesis and improves functional outcome after irradiation. Eur J Neurosci 2007; 25(1): 38– 46.

21. Wojtowicz JM. Irradiation as an experimental tool in studies of adult neurogenesis. Hippocampus 2006; 16(3): 261– 266.

22. Balentova S, Hajtmanova E, Kinclova I et al. Radiation-induced long-term alterations in hippocampus under experimental conditions. Klin Onkol 2012; 25(2): 110– 116.

23. Kazda T, Jancalek R, Pospisil P et al. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy. Radiat Oncol 2014; 9: 139. doi: 10.1186/ 1748- 717X- 9- 139.

24. Gondi V, Pugh SL, Tome WA et al. Preservation of memory with conformal avoidance of the hippocampal neural stem- cell compartment during whole- brain radiotherapy from brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 2014; 32(34): 3810– 3816. doi: 10.1200/ JCO.2014.57.2909.

25. Adamkov M, Halasova E, Kajo K et al. Survivin: a promising marker in breast carcinoma. Neoplasma 2010; 57(6): 572– 577.

26. Adamkov M, Halasova E, Rajcani J et al. Relation between expression pattern of p53 and survivin in cutaneous basal cell carcinomas. Med Sci Monit 2011; 17(3): BR74– BR80.

27. Halasova E, Adamkov M, Matakova T et al. Lung cancer incidence and survival in chromium exposed individuals with respect to expression of anti-apoptotic protein survivin and tumor supressor p53 protein. Eur J Med Res 2010; 15 (Suppl 2): 55– 59.

28. Balentova S, Hajtmanova E, Plevkova J et al. Fractionated irradiation-induced altered spatio- temporal cell distribution in the rat forebrain. Acta Histochem 2013; 115(4): 308– 314. doi: 10.1016/ j.acthis.2012.09.001.

29. Sundholm- Peters NL, Yang HK, Goings GE et al. Subvetricular zone neuroblasts emigrate toward cortical lesions. J Neuropathol Exp Neurol 2005; 64(12): 1089– 1100.

30. Sano K, Sato M, Tanaka R. Radiation-induced apoptosis and injury of oligodendrocytes on neonatal rat brains. Clin Neurol Neurosur 1997; 99 (Suppl 1): S117.

31. Chow BM, Li YQ, Wong CS. Radiation-induced apoptosis in the central nervous system is p53- dependent. Cell Death Differ 2000; 7(8): 712– 720.

32. Kurita H, Kawahara N, Asai A et al. Radiation-induced apoptosis of oligodendrocytes in the adult rat brain. Neurol Res 2001; 23(8): 869– 874.

33. Mildenberger M, Beach TG, McGeer EG et al. An animal model of prophylactic cranial irradiation: histological effects at acute, early and delayed stages. Int J Radiat Oncol Biol Phys 1990; 18(5): 1051– 1060.

34. Shinohara C, Gobbel GT, Lamborn KR et al. Apoptosis in the subependyma of young adult rats after single and fractionated doses of X-rays. Cancer Res 1997; 57(13): 2694– 2702.

35. Hwang SY, Jung JS, Kim TH et al. Ionizing radiation induces astrocyte gliosis through microglia activation. Neurobiol Dis 2006; 21(3): 457– 467.