Radiation-induced cognitive dysfunction: An experimental model in the old rat

Lamproglou, Ioannis; Chen, Qi-Ming; Boisserie, G.; Mazeron, Jean‐Jacques; Poisson, M; Baillet, F; Poncin, Monique Le; Delattre, Jean‐Yves

doi:10.1016/0360-3016(94)00332-f

Cited by 52 publications

(35 citation statements)

References 8 publications

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“…In the laboratory, rats irradiated at four months of age show deficits in a non-hippocampal dependent task, novel object recognition, as well as in hippocampal-dependent maze performance (52,53). To date, only one laboratory has compared the development of cognitive deficits in irradiated old rodents versus irradiated young rodents (29,30), assessing a limited array of cognitive functions. These earlier studies demonstrated that WBI induced progressive and irreversible memory dysfunction in 18 month old rats, whereas the deficit was reversible in rats irradiated at 45 days or four months of age.…”

Section: Discussionmentioning

confidence: 99%

“…The decrease in overall microglial density concomitant with the increase in the number of activated microglia after WBI demonstrates a striking pro-inflammatory microenvironment in the SGZ across ages; in old rats approximately 75% of all microglia are activated ( Figure 4E,F). Such chronic brain inflammation has been shown to be deleterious for function in many models of aging-related neurodegenerative diseases (55,56), and may contribute to more severe and prolonged WBI-induced cognitive dysfunction in older animals (29,30). Moreover, although the role of microglia in a proinflammatory response has been investigated more extensively, microglia also serve trophic functions by producing and secreting neurotrophic peptides (61,62).…”

Section: Discussionmentioning

confidence: 99%

“…Experimental studies of stroke, traumatic brain injury, exogenous cytokine administration, and axotomy support the hypothesis that aging impacts the intensity and duration of brain inflammation and glial activation following challenges (23)(24)(25)(26)(27)(28). Moreover, evidence that old age impacts the duration of some radiation-induced cognitive deficits in rodents (29,30) suggests greater radiation-induced injury in older rats. These basal and injury-induced differences between young adult and older brains indicate that radiation-induced brain injury may be both quantitatively greater and mechanistically different in middle-age and elderly patients.…”

Section: Introductionmentioning

confidence: 85%

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Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

Schindler¹,

Forbes²,

Robbins³

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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Purpose-To assess the impact of aging on the radiation response in the adult rat brain.Methods and Materials-Male rats 8, 18, or 28 months of age received a single 10Gy dose of whole brain irradiation (WBI). The hippocampal dentate gyrus (DG) was analyzed one and ten weeks later for sensitive neurobiological markers associated with radiation-induced damage: changes in the density of proliferating cells, immature neurons, total microglia, and activated microglia.Results-A significant reduction in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased following WBI in young rats but not in old rats. Total microglial number decreased following WBI at all ages but microglial activation increased markedly, particularly in older animals.Conclusions-Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in the number of immature neurons following WBI but have a greater inflammatory response. The latter may play an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 85%

See 1 more Smart Citation

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

Schindler¹,

Forbes²,

Robbins³

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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“…11,12 To better understand the pathogenesis of early changes after brain irradiation, it is very important to establish an animal model that allows detailed examinations of cognitive dysfunction along with the accompanying histopathologic changes.…”

mentioning

confidence: 99%

An Experimental Study of Acute Radiation-Induced Cognitive Dysfunction in a Young Rat Model

Liu¹,

Xiao²,

Liu³

et al. 2009

AJNR Am J Neuroradiol

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“…The high toxicity of low doses of 56 Fe particles leads to shortened latency for age-like cognitive deficits, in contrast to chronic cognitive impairments induced by clinical brain irradiation schemes (19,20). At 1 month after 1.5 Gy whole-body 56 Fe irradiation, analysis of the Morris water maze behavioral tests in rats revealed deterioration of spatial learning and memory (3).…”

Section: Discussionmentioning

confidence: 99%

Neuroimaging assessment of memory‐related brain structures in a rat model of acute space‐like radiation

Huang¹,

Smith²,

Cummings³

et al. 2009

Magnetic Resonance Imaging

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Purpose: To investigate the acute effects on the central nervous system (CNS) of 56 Fe radiation, a component of high-energy charged particles (HZE) in space radiation, using quantitative magnetic resonance imaging (MRI) noninvasively. Materials and Methods:Sprague-Dawley rats were exposed to whole-brain 56 Fe (0, 1, 2, and 4 Gy). At 1 week postirradiation, MRI scans were made using T2-weighted (T2WI), diffusion-weighted (DWI), and contrast enhanced T1-(CET1) imaging. T2 relaxation time and apparent diffusion coefficient (ADC) values were obtained from memoryrelated brain regions of interest (ROIs). Histopathology was correlated using ex vivo tissues. Results:No overt abnormalities were visualized using T2WI and DWI at 1 week postradiation. CET1 values did not differ significantly between the irradiated and control animals. Compared to 0 Gy, there were significant prolongations in T2 values and reductions in ADC after irradiation. In the absence of evident neuronal pathology, immunohistochemistry revealed astrocytic activation in 4 Gy animals. Conclusion:At 1 week after whole-brain 56 Fe exposure, T2 and ADC values can differentiate radiosensitivity in regions critical for hippocampal-related memory. MRI may provide noninvasive assessment of the initial molecular/cellular disturbances in vivo after HZE irradiation.

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Radiation-induced cognitive dysfunction: An experimental model in the old rat

Cited by 52 publications

References 8 publications

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

An Experimental Study of Acute Radiation-Induced Cognitive Dysfunction in a Young Rat Model

Neuroimaging assessment of memory‐related brain structures in a rat model of acute space‐like radiation

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