Effect of whole-brain irradiation on the specific brain regions in a rat model: Metabolic and histopathological changes.
Effect of ionizing radiation on the brain affects neuronal, glial, and endothelial cell population and lead to significant morphological, metabolic, and functional deficits. In the present study we investigated a dose- and time-dependent correlation between radiation-induced metabolic and histopathological changes. Adult male Wistar rats received a total dose of 35Gy delivered in 7 fractions (dose 5Gy per fraction) once per week in the same weekday during 7 consecutive weeks. Proton magnetic resonance spectroscopy (1H MRS), histochemistry, immunohistochemistry and confocal microscopy were used to determine whether radiation-induced alteration of the brain metabolites correlates with appropriate histopathological changes of neurogenesis and glial cell response in 2 neurogenic regions: the hippocampal dentate gyrus (DG) and the subventricular zone-olfactory bulb axis (SVZ-OB axis). Evaluation of the brain metabolites 18-19 weeks after irradiation performed by1H MRS revealed a significant decrease in the total N-acetylaspartate to total creatine (tNAA/tCr) ratio in the striatum and OB. A significant decline of gamma-aminobutyric acid to tCr (GABA/tCr) ratio was seen in the OB and hippocampus. MR revealed absence of gross inflammatory or necrotic lesions in these regions. Image analysis of the brain sections 18-21 weeks after the exposure showed a radiation-induced increase of neurodegeneration, inhibition of neurogenesis and strong resemblance to the reactive astrogliosis. Results showed that fractionated whole-brain irradiation led to the changes in neurotransmission and to the loss of neuronal viability in vivo. Metabolic changes were closely associated with histopathological findings, i.e. initiation of neuronal cell death, inhibition of neurogenesis and strong response of astrocytes indicated development of late radiation-induced changes.
Institute of Histology and Embryology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4, 036 01 Martin, Slovak Republic. Electronic address: balentova@jfmed.uniba.sk.
Soňa
S
Bálentová
Division of Neurosciences, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4D, 036 01 Martin, Slovak Republic.
Petra
P
Hnilicová
Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4D, 036 01 Martin, Slovak Republic.
Dagmar
D
Kalenská
Department of Radiotherapy and Oncology, Martin University Hospital, Kollárova 2, 036 59 Martin, Slovak Republic.
Peter
P
Murín
Department of Radiotherapy and Oncology, Martin University Hospital, Kollárova 2, 036 59 Martin, Slovak Republic.
Eva
E
Hajtmanová
Division of Neurosciences, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4D, 036 01 Martin, Slovak Republic.
Ján
J
Lehotský
Institute of Histology and Embryology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4, 036 01 Martin, Slovak Republic.
Marian
M
Adamkov
D000818:Animals; D001253:Astrocytes / Q000528:radiation effects; D001835:Body Weight / Q000528:radiation effects; D001921:Brain / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects*; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D000089622:Doublecortin Domain Proteins; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000528:radiation effects; D009474:Neurons / Q000528:radiation effects; D009479:Neuropeptides / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D009929:Organ Size / Q000528:radiation effects; D066244:Proton Magnetic Resonance Spectroscopy; D017208:Rats, Wistar
D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
(1)H MRS; Dentate gyrus; Fractionated irradiation; Neurogenesis; Radiation-induced injury; SVZ-OB axis