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

Bálentová, Soňa; Hnilicová, Petra; Kalenská, Dagmar; Muríň, Peter; Hajtmanová, Eva; Lehotský, Ján; Adamkov, Marián

doi:10.1016/j.neuro.2017.03.005

Cited by 29 publications

(19 citation statements)

References 62 publications

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“…RT aims to destroy the residual GBM cells at the resection border and prevent the disease relapse, but it has wide biological effects on different molecular and physiological parameters in the irradiated brain tissue as well ( 6 ). Negative side effects of X-ray radiation include: increased permeability of the blood-brain barrier ( 7 , 8 ); brain necrosis ( 9 ); morphological changes, microvascular injury, and activation of astrocytes after irradiation of mouse brain ( 10 ); metabolic and histopathological changes in the specific rat brain regions ( 11 ); suppressed cell proliferation in the hippocampal subgranular zone ( 12 ) and long-term neurocognitive impairment ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Radiation Effects on Brain Extracellular Matrix

Grigorieva

2020

Front. Oncol.

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Radiotherapy is an important therapeutic approach to treating malignant tumors of different localization, including brain cancer. Glioblastoma multiforme (GBM) represents the most aggressive brain tumor, which develops relapsed disease during the 1st year after the surgical removal of the primary node, in spite of active adjuvant radiochemotherapy. More and more evidence suggests that the treatment's success might be determined by the balance of expected antitumor effects of the treatment and its non-targeted side effects on the surrounding brain tissue. Radiation-induced damage of the GBM microenvironment might create tumor-susceptible niche facilitating proliferation and invasion of the residual glioma cells and the disease relapse. Understanding of molecular mechanisms of radiation-induced changes in brain ECM might help to reconsider and improve conventional anti-glioblastoma radiotherapy, taking into account the balance between its antitumor and ECM-destructing activities. Although little is currently known about the radiation-induced changes in brain ECM, this review summarizes current knowledge about irradiation effects onto the main components of brain ECM such as proteoglycans, glycosaminoglycans, glycoproteins, and the enzymes responsible for their modification and degradation.

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Section: Introductionmentioning

confidence: 99%

Radiation Effects on Brain Extracellular Matrix

Grigorieva

2020

Front. Oncol.

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“…The hippocampus is the main structure associated with memory and cognition, and thus the most studied after brain irradiation. Authors have proposed that the ablation of hippocampal neurogenesis plays a crucial role in cognitive impairment after radiation [3,4]. It has also been suggested that the cellular mechanism underlying cognitive de cit involves alterations in receptors related to synaptic plasticity.…”

Section: Introductionmentioning

confidence: 99%

Whole-brain irradiation differentially modifies neurotransmitters levels and receptors in the hypothalamus and the prefrontal cortex.

PEREZ

Montes

Sánchez-Hernández

et al. 2020

Preprint

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Background: Whole-brain radiotherapy is a primary treatment for brain tumors and brain metastasis, but it also induces long-term undesired effects. Since cognitive impairment can occur, research on the etiology of secondary effects has focused on the hippocampus. Often overlooked, the hypothalamus controls critical homeostatic functions, some of which are also susceptible after whole-brain radiotherapy. Therefore, using whole-brain irradiation (WBI) in a rat model, we measured neurotransmitters and receptors in the hypothalamus. The prefrontal cortex and brainstem were also analyzed since they are highly connected to the hypothalamus and its regulatory processes.Methods: Male Wistar rats were exposed to WBI with 11 Gy (Biologically Equivalent Dose= 72Gy). After one month, we evaluated changes in gamma-aminobutyric acid (GABA), glycine, taurine, aspartate, glutamate, and glutamine in the hypothalamus, prefrontal cortex, and brainstem according to an HPLC method. Ratios of Glutamate/GABA and Glutamine/Glutamate were calculated. Through Western Blott analysis, we measured the expression of GABAa and GABAb receptors, and NR1 and NR2A subunits of NMDA receptors. Changes were analyzed comparing results with sham controls using the non-parametric Mann-Whitney U test (p<0.05).Results: WBI with 11Gy induced significantly lower levels of GABA, glycine, taurine, aspartate, and GABAa receptor in the hypothalamus. Also, in the hypothalamus, a higher Glutamate/GABA ratio was found after irradiation. In the prefrontal cortex, WBI induced significant increases of glutamine and glutamate, Glutamine/Glutamate ratio, and increased expression of both GABAa receptor and NMDA receptor NR1 subunit. The brainstem showed no statistically significant changes after irradiation.Conclusion: Our findings confirm that WBI can affect rat brain regions differently and opens new avenues for study. After one month, WBI decreases inhibitory neurotransmission in the hypothalamus and, conversely, increases excitatory neurotransmission in the prefrontal cortex. Increments in Glutamate/GABA in the hypothalamus and Glutamine/Glutamate in the frontal cortex indicate a neurochemical imbalance. Found changes could be related to several reported radiotherapy secondary effects, suggesting new prospects for therapeutic targets.

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“…Therefore, investigating the early metabolic characterization of brain tissues following irradiation may present clues to the mechanism of radiation‐induced brain injury and modify the therapeutic strategy. In recent years, magnetic resonance spectroscopy (MRS) has been used to measure the metabolic changes in radiation‐induced brain injury, and has suggested that choline/creatine and N ‐acetylaspartate/creatine are significantly decreased in clinical patients and rats following irradiation (Chen, Cheng, & Zhou, ; Bálentová et al, ; Sundgren et al, ). However, the earliest time point of monitoring these changes based on MRS was at week 3 of radiation exposure (Sundgren et al, ).…”

Section: Introductionmentioning

confidence: 99%

Early metabolic characterization of brain tissues after whole body radiation based on gas chromatography–mass spectrometry in a rat model

Yao

Cao

et al. 2018

Biomedical Chromatography

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Radiation-induced brain injury involves acute, early delayed and late delayed damage based on the time-course and clinical manifestations. The acute symptoms are mostly transient and reversible, whereas the late delayed radiation-induced changes are progressive and irreversible. Therefore, evaluation of the organ-specific early response to ionizing radiation exposure is necessary for improving treatment strategies and minimizing possible damage at an early stage after radiation exposure. In the current study, the gas chromatography-mass spectrometry technique based on metabolomics coupled with metabolic correlation network was applied to investigate the early metabolic characterization of rat brain tissues following irradiation. Our findings showed that the metabolic response to irradiation was not just limited to the variations of individual metabolite levels, but also accompanied by alterations of network correlations among various metabolites. Metabolite clustering indicated that energy metabolism disorder and inflammation response were induced following radiation exposure. The correlation networks revealed that the strong positive correlations of differential metabolites were highly reduced and significant negative linkages were highlighted in irradiated groups even without statistical changes in metabolic levels. Our findings provided new insights into our understanding of the radiation-induced acute brain injury mechanism and clues as to the therapy target for clinical applications.

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

Cited by 29 publications

References 62 publications

Radiation Effects on Brain Extracellular Matrix

Radiation Effects on Brain Extracellular Matrix

Whole-brain irradiation differentially modifies neurotransmitters levels and receptors in the hypothalamus and the prefrontal cortex.

Early metabolic characterization of brain tissues after whole body radiation based on gas chromatography–mass spectrometry in a rat model

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