Sublethal total body irradiation leads to early cerebellar damage and oxidative stress

Curr Neurovasc Res. 2010 May;7(2):125-35. doi: 10.2174/156720210791184880.

Abstract

The present study aimed at identifying early damage index in the cerebellum following total body irradiation (TBI). Adult male CD2F1 mice (n=18) with or without TBI challenge (8.5 Gy irradiation) were assessed for histology and expression of selected immunohistochemical markers including malondiadehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), protein 53 (p53), vascular endothelial growth factor receptor 2 (VEGF-R2), CD45, calbindin D-28k (CB- 28) and vesicular glutamate transport-2 (VGLUT2) in cerebellar folia II to IV. Compared to sham-controls, TBI significantly increased vacuolization of the molecular layer. At high magnification, deformed fiber-like structures were found along with the empty matrix space. Necrotic Purkinje cells were identified on 3.5 days after TBI, but not on 1 day. Purkinje cell count was reduced significantly 3.5 days after TBI. Compared with sham control, overall intensities of MDA and 8-OHdG immunoreactivities were increased dramatically on 1 and 3.5 days after TBI. Expression of VEGF-R2 was identified to be co-localized with 8-OHdG after TBI. This validates microvessel endothelial damage. The p53 immunoreactivities mainly deposited in the granular layer and microvessels after TBI and co-localization of the p53 with the CD45, both which were found within the microvessels. After TBI, CB28 expression decreased whereas the VGLUT2 expression increased significantly; Purkinje cells exhibited a reduced body size and deformity of dendritic arbor, delineated by CB28 immunoreactivity. Substantial damage to the cerebellum can be detectable as early as 1- 3.5 days in adult animals following sublethal TBI. Oxidative stress, inflammatory response and calcium neurotoxicity-associated mechanisms are involved in radiation-induced neuronal damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Analysis of Variance
  • Animals
  • Brain Injuries / etiology*
  • Brain Injuries / pathology*
  • Calbindins
  • Cerebellum / pathology
  • Cerebellum / radiation effects*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Gene Expression Regulation / radiation effects
  • Imaging, Three-Dimensional / methods
  • Leukocyte Common Antigens / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Oxidative Stress / radiation effects*
  • S100 Calcium Binding Protein G / metabolism
  • Time Factors
  • Tumor Suppressor Protein p53 / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Vesicular Glutamate Transport Protein 2 / metabolism
  • Whole-Body Irradiation / adverse effects*

Substances

  • Calbindins
  • S100 Calcium Binding Protein G
  • Slc17a6 protein, rat
  • Tumor Suppressor Protein p53
  • Vesicular Glutamate Transport Protein 2
  • Malondialdehyde
  • 8-Hydroxy-2'-Deoxyguanosine
  • Vascular Endothelial Growth Factor Receptor-2
  • Leukocyte Common Antigens
  • Deoxyguanosine