Radiation-induced brain injury (RII) is a harmful side-effect occurring after conventional radiation therapy (usually fractionated whole-brain irradiation/fWBI) of patients with cerebral tumors and metastases. An important role in the quality of patients' lives plays cognitive, executive, and emotional functions, regulation on which are involved in frontal cortices pathways. This study assessed the morphologic and metabolic alterations in the rodent frontal cortex caused by fWBI with the total dose of 32 Gy in 4 fractions performed by linear accelerator Clinac iX. Nine male Wistar rats underwent radiation procedures, whereas the other nine rats were investigated as a sham-irradiated group. All eighteen animals were examined using magnetic resonance (MR) in three intervals - before, on 2nd, and 70th day after sham/irradiation. After ten weeks of surviving, all rats underwent histopathological analysis determined by image analysis of immunofluorescent stained sections in the frontal cortex. MR examination was performed on 7T MR scanner Bruker BioSpec 70/20 and consisted of MR-volumetry, T2 relaxometry, and single-voxel proton-1 MR spectroscopy localized in the frontal cortex. Both tissue volume and T2 relaxation time of the frontal cortex were significantly lower in animals after 2 and 70 days of exposure than in controls; however, there were no differences between irradiated groups. Similarly, in animals' frontal cortex after fWBI, increased levels of myoinositol and glutamate/glutamine ratios were observed. Ratios of N-acetyl-aspartate, choline, and peaks of lactate and lipids did not change between groups. The histopathological analysis of the frontal cortex showed increased signs of neurodegeneration and a slight increase in astrocytes and microglia in exposed animals. Early (2 days, 10 weeks) after clinically relevant fWBI were in the frontal cortices of exposed rodents confirmed morphologic and metabolic changes indicating neurodegenerative changes, initializing cerebral atrophy, and evident signs of endothelial disruption and dysregulated neurotransmission that may cause a wide range of functional as well as cognitive deficits.
Keywords: Fractionated whole-brain irradiation; Frontal cortex; Histological staining; Magnetic resonance; Radiation-induced brain injury.
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