Maintenance of white matter integrity in a rat model of radiation-induced cognitive impairment

Radiation therapy is used widely to treat primary and metastatic brain tumors, but also can lead to delayed neurological complications. Since maintenance of myelin integrity is important for cognitive function, the present study used a rat model that demonstrates spatial learning and memory impairment 12 months following fractionated whole-brain irradiation (WBI) at middle age to investigate WBI-induced myelin changes. In this model, 12-month Fischer 344 x Brown Norway rats received 9 fractions of 5 Gy delivered over 4.5 weeks (WBI rats); Sham-IR rats received anesthesia only. Twelve months later, the brains were collected and measures of white matter integrity were quantified. Qualitative observation did not reveal white matter necrosis one year post-WBI. In addition, the size of major forebrain commissures, the number of oligodendrocytes, the size and number of myelinated axons, and the thickness of myelin sheaths did not differ between the two groups. In summary, both the gross morphology and the structural integrity of myelin were preserved one year following fractionated WBI in a rodent model of radiation-induced cognitive impairment. Imaging studies with advanced techniques including diffusion tensor imaging may be required to elucidate the neurobiological changes associated with the cognitive impairment in this model.