Altered brain metabolism after whole body irradiation in mice: A preliminary in vivo<sup>1</sup>H MRS study

Rana, Poonam; Khan, Asia; Modi, Shilpi; Kumar, B.S. Hemanth; Javed, Saleem; Tripathi, R. P.; Khushu, Subash

doi:10.3109/09553002.2013.734944

Cited by 11 publications

(18 citation statements)

References 43 publications

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“…Indeed, even within the CNS, the complex interrelationships between neuroinflammatory responses, mitochondrial redox mechanisms and different cell populations complicate the understanding of responses to ionising radiation at different doses [24]. It is clear, however, that ionising radiation can impact nucleic acids [69], [70], neurovascular permeability [71], [72], [73], induce ROS/RNS [21], [67], [74], [75] and elicit a neuroinflammatory response [76], [77], [78], all of which can manifest as radiation-induced injury.…”

Section: The Impact Of High Dose Ionising Radiation On the Cnsmentioning

confidence: 99%

The impact of high and low dose ionising radiation on the central nervous system

et al. 2016

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Responses of the central nervous system (CNS) to stressors and injuries, such as ionising radiation, are modulated by the concomitant responses of the brains innate immune effector cells, microglia. Exposure to high doses of ionising radiation in brain tissue leads to the expression and release of biochemical mediators of ‘neuroinflammation’, such as pro-inflammatory cytokines and reactive oxygen species (ROS), leading to tissue destruction. Contrastingly, low dose ionising radiation may reduce vulnerability to subsequent exposure of ionising radiation, largely through the stimulation of adaptive responses, such as antioxidant defences. These disparate responses may be reflective of non-linear differential microglial activation at low and high doses, manifesting as an anti-inflammatory or pro-inflammatory functional state. Biomarkers of pathology in the brain, such as the mitochondrial Translocator Protein 18 kDa (TSPO), have facilitated in vivo characterisation of microglial activation and ‘neuroinflammation’ in many pathological states of the CNS, though the exact function of TSPO in these responses remains elusive. Based on the known responsiveness of TSPO expression to a wide range of noxious stimuli, we discuss TSPO as a potential biomarker of radiation-induced effects.

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Section: The Impact Of High Dose Ionising Radiation On the Cnsmentioning

confidence: 99%

The impact of high and low dose ionising radiation on the central nervous system

et al. 2016

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“…The sensitivity of the hippocampus to early gamma radiation effects is consistent with other radiation DTI studies (Trivedi et al, 2012). The reduction in myoinositol and taurine ratios in the cortical–hippocampus region 2–10 days after whole-body X-ray irradiation (8 Gy) in young adult mice using in vivo proton nuclear magnetic resonance spectroscopy (MRS) suggests perturbations in astrocytes or microglial activation (Rana et al, 2013). The specific involvement of the hippocampus is further supported by the recently reported memory preservation at 4 and 6 months follow up in patients with brain metastases receiving intensity-modulated radiotherapy to reduce exposure to the hippocampus (Gondi et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Impairment in Extinction of Contextual and Cued Fear Following Post-Training Whole-Body Irradiation

Marzulla

Raber

2014

Front. Behav. Neurosci.

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Because of the use of radiation in cancer therapy, the risk of nuclear contamination from power plants, military conflicts, and terrorism, there is a compelling scientific and public health interest in the effects of environmental radiation exposure on brain function, in particular hippocampal function and learning and memory. Previous studies have emphasized changes in learning and memory following radiation exposure. These approaches have ignored the question of how radiation exposure might impact recently acquired memories, which might be acquired under traumatic circumstances (cancer treatment, nuclear disaster, etc.). To address the question of how radiation exposure might affect the processing and recall of recently acquired memories, we employed a fear conditioning paradigm wherein animals were trained, and subsequently irradiated (whole-body X-ray irradiation) 24 h later. Animals were given 2 weeks to recover, and were tested for retention and extinction of hippocampus-dependent contextual fear conditioning or hippocampus-independent cued fear conditioning. Exposure to irradiation following training was associated with reduced daily increases in body weights over the 22-days of the study and resulted in greater freezing levels and aberrant extinction 2 weeks later. This was also observed when the intensity of the training protocol was increased. Cued freezing levels and measures of anxiety 2 weeks after training were also higher in irradiated than sham-irradiated mice. In contrast to contextual freezing levels, cued freezing levels were even higher in irradiated mice receiving 5 shocks during training than sham-irradiated mice receiving 10 shocks during training. In addition, the effects of radiation on extinction of contextual fear were more profound than those on the extinction of cued fear. Thus, whole-body irradiation elevates contextual and cued fear memory recall.

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“…The variations in metabolism may be due to the radiation-induced neuronal damage, the neuroinflammatory response triggered in microglial cells, as well as the blood-brain barrier disruption and repair processes. [2021]…”

Section: Discussionmentioning

confidence: 99%

Long-term Brain Tissue Monitoring after Semi-brain Irradiation in Rats Using Proton Magnetic Resonance Spectroscopy

Chen

Cheng

Zhou

2017

Chinese Medical Journal

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Background:In head and neck neoplasm survivors treated with brain irradiation, metabolic alterations would occur in the radiation-induced injury area. The mechanism of these metabolic alterations has not been fully understood, while the alternations could be sensitively detected by proton (1H) nuclear magnetic resonance spectroscopy (MRS). In this study, we investigated the metabolic characteristics of radiation-induced brain injury through a long-term follow-up after radiation treatment using MRS in vivo.Methods:A total of 12 adult Sprague-Dawley rats received a single dose of 30 Gy radiation treatment to semi-brain (field size: 1.0 cm × 2.0 cm; anterior limit: binocular posterior inner canthus connection; posterior limit: external acoustic meatus connection; internal limit: sagittal suture). Conventional magnetic resonance imaging and single-voxel 1H-MRS were performed at different time points (in month 0 before irradiation as well as in the 1st, 3rd, 5th, 7th, and 9th months after irradiation) to investigate the alternations in irradiation field. N-acetylaspartate/choline (NAA/Cho), NAA/creatinine (Cr), and Cho/Cr ratios were measured in the bilateral hippocampus and quantitatively analyzed with a repeated-measures mixed-effects model and multiple comparison test.Results:Significant changes in the ratios of NAA/Cho (F = 57.37, Pg < 0.001), NAA/Cr (F = 54.49, Pg < 0.001), and Cho/Cr (F = 9.78, Pg = 0.005) between the hippocampus region of the irradiated semi-brain and the contralateral semi-brain were observed. There were significant differences in NAA/Cho (F = 9.17, Pt < 0.001) and NAA/Cr (F = 13.04, Pt < 0.001) ratios over time. The tendency of NAA/Cr to change with time showed no significant difference between the irradiated and contralateral sides. Nevertheless, there were significant differences in the Cho/Cr ratio between these two sides.Conclusions:MRS can sensitively detect metabolic alternations. Significant changes of metabolites ratio in the first few months after radiation treatment reflect the metabolic disturbance in the acute and early-delayed stages of radiation-induced brain injuries.

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Altered brain metabolism after whole body irradiation in mice: A preliminary in vivo¹H MRS study

Abstract: The results of this preliminary study suggest that the alteration/reduction in the mI and Tau concentration may be associated with physiological perturbations in astrocytes or radiation induced neuro-inflammatory response triggered in microglial cell.

Cited by 11 publications

References 43 publications

The impact of high and low dose ionising radiation on the central nervous system

The impact of high and low dose ionising radiation on the central nervous system

Impairment in Extinction of Contextual and Cued Fear Following Post-Training Whole-Body Irradiation

Long-term Brain Tissue Monitoring after Semi-brain Irradiation in Rats Using Proton Magnetic Resonance Spectroscopy

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Altered brain metabolism after whole body irradiation in mice: A preliminary in vivo1H MRS study

Abstract: The results of this preliminary study suggest that the alteration/reduction in the mI and Tau concentration may be associated with physiological perturbations in astrocytes or radiation induced neuro-inflammatory response triggered in microglial cell.

Cited by 11 publications

References 43 publications

The impact of high and low dose ionising radiation on the central nervous system

The impact of high and low dose ionising radiation on the central nervous system

Impairment in Extinction of Contextual and Cued Fear Following Post-Training Whole-Body Irradiation

Long-term Brain Tissue Monitoring after Semi-brain Irradiation in Rats Using Proton Magnetic Resonance Spectroscopy

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Altered brain metabolism after whole body irradiation in mice: A preliminary in vivo¹H MRS study