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Neurogenesis, exercise, and cognitive late effects of pediatric radiotherapy.

Rodgers SP, Trevino M, Zawaski JA, Gaber MW, Leasure JL - Neural Plast. (2013)

Bottom Line: 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.Potential treatments for cognitive late effects should address both of these conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Houston, Houston, TX 77204, USA.

ABSTRACT
Brain 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.

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Related in: MedlinePlus

Data from our group indicates that measurable imaging changes precede cognitive decline. (a) An image of a rat brain acquired using a 9.4 T MRI. The pink box indicates where 1H MRS was performed. Changes in glutamate, alanine, and lactate preceded cognitive impairments. In addition, FA analysis detected a decrease in volume of the fimbria. (b) An FA map of the rat brain.
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fig2: Data from our group indicates that measurable imaging changes precede cognitive decline. (a) An image of a rat brain acquired using a 9.4 T MRI. The pink box indicates where 1H MRS was performed. Changes in glutamate, alanine, and lactate preceded cognitive impairments. In addition, FA analysis detected a decrease in volume of the fimbria. (b) An FA map of the rat brain.

Mentions: Using this model, we can probe the cellular, chemical, and structural effects of RT that contribute to decreased brain size and cognitive impairments in adulthood. To enhance translational value, we are using imaging techniques to discover RT-induced changes in vivo that predict future cognitive impairments before they manifest. For example, we are using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to assess RT-induced structural changes and 1H magnetic resonance spectroscopy (MRS) to assess chemical changes following RT (see Figure 2). DTI has the added advantage of providing information on fractional anisotropy (FA), a measure of the functional integrity of white matter tracts. Our preliminary 1H MRS findings showed changes in glutamate, alanine, and lactate in RT brains, compared to sham controls. In addition, FA analysis showed a significant decline in fimbria volume and mean fimbria FA value in RT brains compared to controls. These changes were observed three months prior to the detected cognitive changes shown in Figure 3, suggesting that imaging changes can be used as early markers of cognitive decline.


Neurogenesis, exercise, and cognitive late effects of pediatric radiotherapy.

Rodgers SP, Trevino M, Zawaski JA, Gaber MW, Leasure JL - Neural Plast. (2013)

Data from our group indicates that measurable imaging changes precede cognitive decline. (a) An image of a rat brain acquired using a 9.4 T MRI. The pink box indicates where 1H MRS was performed. Changes in glutamate, alanine, and lactate preceded cognitive impairments. In addition, FA analysis detected a decrease in volume of the fimbria. (b) An FA map of the rat brain.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3649702&req=5

fig2: Data from our group indicates that measurable imaging changes precede cognitive decline. (a) An image of a rat brain acquired using a 9.4 T MRI. The pink box indicates where 1H MRS was performed. Changes in glutamate, alanine, and lactate preceded cognitive impairments. In addition, FA analysis detected a decrease in volume of the fimbria. (b) An FA map of the rat brain.
Mentions: Using this model, we can probe the cellular, chemical, and structural effects of RT that contribute to decreased brain size and cognitive impairments in adulthood. To enhance translational value, we are using imaging techniques to discover RT-induced changes in vivo that predict future cognitive impairments before they manifest. For example, we are using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to assess RT-induced structural changes and 1H magnetic resonance spectroscopy (MRS) to assess chemical changes following RT (see Figure 2). DTI has the added advantage of providing information on fractional anisotropy (FA), a measure of the functional integrity of white matter tracts. Our preliminary 1H MRS findings showed changes in glutamate, alanine, and lactate in RT brains, compared to sham controls. In addition, FA analysis showed a significant decline in fimbria volume and mean fimbria FA value in RT brains compared to controls. These changes were observed three months prior to the detected cognitive changes shown in Figure 3, suggesting that imaging changes can be used as early markers of cognitive decline.

Bottom Line: 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.Potential treatments for cognitive late effects should address both of these conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Houston, Houston, TX 77204, USA.

ABSTRACT
Brain 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.

Show MeSH
Related in: MedlinePlus