Effect of whole-brain irradiation on the specific brain regions in a rat model: Metabolic and histopathological changes

• Published in: Neurotoxicology (Park Forest South) 2017-05, Vol.60, p.70-81
• Main Authors: Bálentová, Soňa, Hnilicová, Petra, Kalenská, Dagmar, Murín, Peter, Hajtmanová, Eva, Lehotský, Ján, Adamkov, Marian
• Format: Article
• Language: English
• Subjects: 1H MRS; Animals; Astrocytes; Astrocytes - radiation effects; Body Weight - radiation effects; Brain; Brain - metabolism; Brain - pathology; Brain - radiation effects; Cell death; Confocal microscopy; Corpus Striatum - metabolism; Corpus Striatum - pathology; Corpus Striatum - radiation effects; Creatine; Dentate gyrus; Food irradiation; Fractionated irradiation; Glial cells; Gliosis; Hippocampus; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - radiation effects; Histochemistry; Histopathology; Image analysis; Image processing; Immunohistochemistry; Inflammation; Inhibition; Ionizing radiation; Irradiation; Laboratory animals; Lesions; Magnetic resonance spectroscopy; Male; Metabolites; Microscopy; Microtubule-Associated Proteins - metabolism; Neostriatum; Neurodegeneration; Neurogenesis; Neurogenesis - radiation effects; Neuroimaging; Neuronal-glial interactions; Neurons - radiation effects; Neuropeptides - metabolism; Neurotransmission; Olfactory bulb; Olfactory Bulb - metabolism; Olfactory Bulb - pathology; Olfactory Bulb - radiation effects; Organ Size - radiation effects; Proton magnetic resonance; Proton Magnetic Resonance Spectroscopy; Radiation dosage; Radiation effects; Radiation-induced injury; Rats; Rats, Wistar; Spectroscopy; SVZ-OB axis; Viability; γ-Aminobutyric acid
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2017.03.005

•Fractionated whole-brain irradiation led to metabolic and histopathological changes.•Changes in neurotransmission and loss of neuronal viability were detected by MRI.•Neurodegeneration and strong astrocytic response was seen 6 months after treatment. 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 by 1H 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.