Capillary loss precedes the cognitive impairment induced by fractionated whole-brain irradiation: A potential rat model of vascular dementia

• Published in: Journal of the neurological sciences 2007-06, Vol.257 (1), p.67-71
• Main Authors: Brown, William R, Blair, Robert M, Moody, Dixon M, Thore, Clara R, Ahmed, Stephanie, Robbins, Michael E, Wheeler, Kenneth T
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain irradiation; Brain Ischemia - etiology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Brain Neoplasms - radiotherapy; Capillaries - pathology; Capillaries - physiopathology; Capillaries - radiation effects; Capillary loss; Cerebral Arteries - pathology; Cerebral Arteries - physiopathology; Cerebral Arteries - radiation effects; Cognition Disorders - etiology; Cognition Disorders - pathology; Cognition Disorders - physiopathology; Cognitive function; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Dementia, Vascular - etiology; Dementia, Vascular - pathology; Dementia, Vascular - physiopathology; Disease Models, Animal; Disease Progression; Dose Fractionation; Fractionated dose; Maze Learning - radiation effects; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Radiation Injuries - pathology; Radiation Injuries - physiopathology; Radiotherapy - adverse effects; Rat model; Rats; Rats, Inbred F344; Risk Factors; Time
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2007.01.014

Abstract Brain tumor patients who are long-term survivors after whole-brain irradiation (WBI) often suffer cognitive impairment, including dementia. Although the pathogenic mechanisms remain poorly understood, our studies suggest that radiation-induced cognitive impairment may be a form of vascular dementia. We used a fractionated dose of γ-rays that is biologically similar to that given to brain tumor patients. The brains of adult rats were irradiated with 40 Gy, in eight 5 Gy fractions over 4 weeks. Cognitive function was assessed prior to WBI and up to 9 months post-irradiation using a partially-baited radial arm maze. A significant increase in working memory errors was found in the irradiated rats by two-way ANOVA ( p = 0.0042). The increased errors occurred primarily at 6 and 9 months ( p < 0.05, student's t -test). Vessel density was quantified using a stereology method with computerized image processing and analysis. Vessel density was unchanged 24 h after the last dose, but significantly decreased ( p = 0.002), by approximately 30%, from 10 weeks to 52 weeks. Thus, cognitive impairment arose after brain capillary loss in irradiated rats that show no other gross brain pathology. Capillary loss may play an important role in radiation-induced dementia and this may be a model of vascular dementia.