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Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy.

ABSTRACT: Background:While cranial radiation therapy (CRT) is an effective treatment, healthy areas surrounding irradiation sites are negatively affected. Frontal lobe functions involving attention, processing speed, and inhibition control are impaired. These deficits appear months to years after CRT and impair quality of life. Exercise has been shown to rejuvenate the brain and aid in recovery post-injury through its effects on neurogenesis and cognition. Methods:We developed a juvenile rodent CRT model that reproduces neurocognitive deficits. Next, we utilized the model to test whether exercise ameliorates these deficits. Fischer rats (31 days old) were irradiated with a fractionated dose of 4 Gy × 5 days, trained and tested at 6, 9, and 12 months post-CRT using 5-choice serial reaction time task. After testing, fixed rat brains were imaged using diffusion tensor imaging and immunohistochemistry. Results:CRT caused early and lasting impairments in task acquisition, accuracy, and latency to correct response, as well as causing stunting of growth and changes in brain volume and diffusion. Exercising after irradiation improved acquisition, behavioral control, and processing speed, mitigated the stunting of brain size, and increased brain fiber numbers compared with sedentary CRT values. Further, exercise partially restored global connectome organization, including assortativity and characteristic path length, and while it did not improve the specific regional connections that were lowered by CRT, it appeared to remodel these connections by increasing connectivity between alternate regional pairs. Conclusions:Our data strongly suggest that exercise may be useful in combination with interventions aimed at improving cognitive outcome following pediatric CRT.

SUBMITTER: Sahnoune I

PROVIDER: S-EPMC5892168 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy.

Sahnoune Iman I Inoue Taeko T Kesler Shelli R SR Rodgers Shaefali P SP Sabek Omaima M OM Pedersen Steen E SE Zawaski Janice A JA Nelson Katharine H KH Ris M Douglas MD Leasure J Leigh JL Gaber M Waleed MW

Neuro-oncology 20180401 5

<h4>Background</h4>While cranial radiation therapy (CRT) is an effective treatment, healthy areas surrounding irradiation sites are negatively affected. Frontal lobe functions involving attention, processing speed, and inhibition control are impaired. These deficits appear months to years after CRT and impair quality of life. Exercise has been shown to rejuvenate the brain and aid in recovery post-injury through its effects on neurogenesis and cognition.<h4>Methods</h4>We developed a juvenile ro ...[more]

PMID: 29121259

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Dataset Information

Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy.

Publications

Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy.

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