temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months颞脑脊液动力学和淀粉积累的老鼠大脑的衰老过程从三个三十个月.pdf

Chiu et al. Fluids and Barriers of the CNS 2012, 9:3 FLUIDS AND BARRIERS /content/9/1/3 OF THE CNS RESEARCH Open Access Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months 1 1 1 2 1 1 Catherine Chiu , Miles C Miller , Ilias N Caralopoulos , Michael S Worden , Thomas Brinker , Zachary N Gordon , Conrad E Johanson1 and Gerald D Silverberg1* Abstract Background: Amyloid accumulation in the brain parenchyma is a hallmark of Alzheimer’s disease (AD) and is seen in normal aging. Alterations in cerebrospinal fluid (CSF) dynamics are also associated with normal aging and AD. This study analyzed CSF volume, production and turnover rate in relation to amyloid-beta peptide (Ab) accumulation in the aging rat brain. Methods: Aging Fischer 344/Brown-Norway hybrid rats at 3, 12, 20, and 30 months were studied. CSF production was measured by ventriculo-cisternal perfusion with blue dextran in artificial CSF; CSF volume by MRI; and CSF turnover rate by dividing the CSF production rate by the volume of the CSF space. Ab40 and Ab42 concentrations in the cortex and hippocampus were measured by ELISA. Results: There was a significant linear increase in total cranial CSF volume with age: 3-20 months (p 0.01); 3-30 months (p 0.001). CSF production rate increased from 3-12 months (p 0.01) and decreased from 12-30 months (p 0.05). CSF turnover showed an initial increase from 3 months (9.40 day-1) to 12 months