title: Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus.
abstract: Cranial 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.
authors.affiliation: Department of Psychology, University of Houston, Houston, TX 77204, USA.
authors.forename: Shaefali P
authors.identifier: 0000-0003-3143-7320
authors.initials: SP
authors.lastname: Rodgers
authors.affiliation: Hematology-Oncology Section, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Janice A
authors.initials: JA
authors.lastname: Zawaski
authors.affiliation: Department of Psychology, University of Houston, Houston, TX 77204, USA.
authors.forename: Iman
authors.initials: I
authors.lastname: Sahnoune
authors.affiliation: Department of Psychology, University of Houston, Houston, TX 77204, USA; Department of Biology & Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: J Leigh
authors.identifier: 0000-0002-9014-2525
authors.initials: JL
authors.lastname: Leasure
authors.affiliation: Hematology-Oncology Section, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: M Waleed
authors.identifier: 0000-0002-6192-0367
authors.initials: MW
authors.lastname: Gaber
mesh_terms: D000818:Animals; D001835:Body Weight / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000009:adverse effects*; D006130:Growth Disorders / Q000209:etiology* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar