Effects of ionizing radiation on osseous healing in SAMR1 and SAMP6 mice: a histiological study
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Previous studies have showed effects of irradiation on bone and on fracture healing. This is a histological study of the effect of a combined irradiation/fracture injury model in a strain of aged mice (SAMP6) and controls (SAMR1) and the effects of the radioprotective agent, JP4-039 (a mitochondria targeted GS-nitroxide). Hind legs in SAMR1 and SAMP6 control mice and mice pretreated with JP4-039 were exposed to a single dose of radiation (0 or 20 Gy). Twenty four hours after irradiation, unicortical osseous wounds were created in each proximal tibia. Mice were sacrificed at intervals (14, 21 days), tibias excised, radiographed, and prepared for histology (day 21 only). Tibias were examined and graded histologically for evidence of cortical bridging and intramedullary fibrosis. Irradiated SAMP6 wounds showed significantly diminished cortical bridging and significantly more intramedullary fibrosis. In contrast, JP4-039 showed a statistical trend in ameliorating intramedullary fibrosis in irradiated SAMP6 mice. In control SAMR1 mice, JP4-039 had no significant effect on cortical bridging or fibrosis with the number of replicates available. In summary, SAMP6 mice display diminished capacity to recover from the combined irradiation/fracture injury model, with subgroups pretreated with JP4-039 showing beneficial trends in mitigating irradiation induced injury.
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