바로가기  >

Abstract
Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [64Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [64Cu]Cu-albumin at an infusion rate of 700 nl/min in adult and aged mice (15-25 months old). CSF clearance and paravertebral lymph nodes were quantified after injection and during the stationary phase. Stationary phase of the next day followed the initial perturbed state by injection of 6 ul (1/7 of total CSF volume) and CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 and 123.3 ± 15.6 min in adult and aged mice (p = 0.01), respectively. While the % injected dose of CSF space were higher, the activity of the paravertebral lymph nodes were lower in the aged mice on the next day. [64Cu]Cu-albumin PET enabled us to quantify CSF-lymphatic drainage across all levels of brain spinal cords and to visualize and quantify lymph node activity due to CSF drainage. [64Cu]Cu-albumin PET revealed the age-related decrease of the lymphatic drainage of CSF due to this decreased drainage from the subarachnoid space, especially during the stationary phase, in aged mice.

Affiliations

Azmal Sarker 1, Minseok Suh 2 3 4, Yoori Choi 5 6 7, Ji Yong Park 1 5, Yun-Sang Lee 1 5, Dong Soo Lee 8 9 10 11 12
1Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea.
2Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea. mandu3710@gmail.com.
3Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea. mandu3710@gmail.com.
4Biomedical Research Center, Seoul National University Hospital, Seoul, Korea. mandu3710@gmail.com.
5Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
6Biomedical Research Center, Seoul National University Hospital, Seoul, Korea.
7Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
8Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea. dsl@snu.ac.kr.
9Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea. dsl@snu.ac.kr.
10Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea. dsl@snu.ac.kr.
11Medical Research Center, College of Medicine, Seoul National University, Seoul, Korea. dsl@snu.ac.kr.
12Medical Science and Engineering, School of Convergence Science and Technology, Pohang University of Science and Technology (POSTECH), Pohang, Korea. dsl@snu.ac.kr.