title: Neurobiological responses to stereotactic focal irradiation of the adult rodent hippocampus.
abstract: Radiation effectively treats brain tumors and other pathologies but dose and treatment plans are limited by normal tissue injury, a major cause of morbidity in survivors. Clinically significant normal tissue injury can occur even with therapies that target pathological tissue and limit out-of-target irradiation. Elucidating the mechanisms underlying normal tissue injury is facilitated by studying the effects of focal irradiation and comparing irradiated and un-irradiated tissue in experimental animals. Young adult rats were irradiated using the Leksell Gamma Knife® with a 10 Gy maximum dose directed at the left hippocampus and shaped to minimize irradiation contralaterally. At least 95% of targeted hippocampus received ≥3 Gy, while all points in the contralateral hippocampus received <0.3 Gy. Neuronal and microglial markers of damage were assessed in the targeted and contralateral hemispheres of Gamma Knife®-treated rats and compared to non-irradiated controls. Acute cell death and sustained changes in neurogenesis and in microglia occurred in the dentate gyrus of the targeted, but not the contralateral, hippocampus, providing experimental evidence that focal irradiation at doses received by peri-target regions during targeted radiation therapy produces robust normal tissue responses. Additional studies using this approach will facilitate assessment of in vivo dose responses and the cellular and molecular mechanisms of radiation-induced brain injury.
authors.affiliation: Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Schindler
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Bourland
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Forbes
authors.forename: Kun
authors.initials: K
authors.lastname: Hua
authors.forename: David R
authors.initials: DR
authors.lastname: Riddle
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D053331:Ectodysplasins / Q000378:metabolism; D007839:Functional Laterality / Q000528:radiation effects; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006624:Hippocampus / Q000473:pathology* / Q000528:radiation effects*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000528:radiation effects; D055495:Neurogenesis / Q000528:radiation effects; D051381:Rats; D011916:Rats, Inbred F344; D013238:Stereotaxic Techniques; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D053331:Ectodysplasins; D000949:Histocompatibility Antigens Class II; D008840:Microfilament Proteins; D001973:Bromodeoxyuridine