Browsing by Author "Gaber, M. Waleed"
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Item Neurogenesis, exercise, and cognitive late effects of pediatric radiotherapy(Neural Plasticity, 2013-04) Rodgers, Shaefali P.; Trevino, Melissa; Zawaski, Janice A.; Gaber, M. Waleed; Leasure, J. LeighBrain cancer is a common type of childhood malignancy, and radiotherapy (RT) is a mainstay of treatment. RT is effective for tumor eradication, and survival rates are high. However, RT damages the brain and disrupts ongoing developmental processes, resulting in debilitating cognitive “late” effects that may take years to fully manifest. These late effects likely derive from a long-term decrement in cell proliferation, combined with a neural environment that is hostile to plasticity, both of which are induced by RT. Long-term suppression of cell proliferation deprives the brain of the raw materials needed for optimum cognitive performance (such as new neurons in the hippocampus and new glia in frontal cortex), while chronic inflammation and dearth of trophic substances (such as growth hormone) limit neuroplastic potential in existing circuitry. Potential treatments for cognitive late effects should address both of these conditions. Exercise represents one such potential treatment, since it has the capacity to enhance cell proliferation, as well as to promote a neural milieu permissive for plasticity. Here, we review the evidence that cognitive late effects can be traced to RT-induced suppression of cell proliferation and hostile environmental conditions, as well as emerging evidence that exercise may be effective as an independent or adjuvant therapy.Item Radiation-induced growth retardation and microstructural and metabolite abnormalities in the hippcampus(Neural Plasticity, 2016-05) Rodgers, Shaefali P.; Zawaski, Janice A.; Sahnoune, Iman; Leasure, J. Leigh; Gaber, M. WaleedCranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT.Item The Effects of Exercise on Neurocognitive Impairments in a Translational Model of Pediatric Radiotherapy(2015-05) Sahnoune, Iman; Leasure, J. Leigh; Gaber, M. Waleed; Fletcher, Jack M.Cranial radiation therapy (CRT) is used as a treatment for brain malignancies that are not easily accessible and would provide significant risk to the patient through invasive methods like surgery. While CRT has been shown to be effective as a treatment, healthy areas surrounding the irradiation sites are detrimentally affected. Frontal lobe functions are impaired, particularly the domains of attention, processing speed and inhibition control. These deficits often manifest months to years after radiation and significantly impair quality-of-life over time. Exercise is proposed as an adjuvant therapy to ameliorate the deleterious effects of radiation. We established a rodent model of the neurocognitive effects of CRT. Adolescent Fischer rats were irradiated with a fractionated dose of 20Gy (4Gy x 5 days). We showed lasting neurocognitive impairments in the 5-Choice Serial Reaction Time Task (5-CSRTT), a test that simultaneously measures several cognitive modalities. We investigated whether voluntary exercise could ameliorate these impairments by having physical activity groups exercise from the week after irradiation until behavioral training. We found that exercise significantly ameliorated performance at both 3 months and 6 months post-RT in accuracy, premature responses, and latency to correct responses, along with the number of trials taken to complete stages during training. Our data suggests that exercise significantly mitigates neurocognitive deficits sustained by cranial radiation therapy in our translational model of pediatric radiotherapy.