Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea.
Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
Sci Rep. 2023 Aug 9;13(1):12930. doi: 10.1038/s41598-023-39903-y.
Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [Cu]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. [Cu]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. [Cu]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.
年龄相关性认知能力下降与脑脊液压通过脑膜淋巴管的功能障碍性引流有关。在这项研究中，我们在小鼠中应用了鞘内[Cu]Cu-白蛋白正电子发射断层扫描（PET）来评估脑脊液的淋巴引流及其随年龄的变化。在以 700 nl/min 的输注速率鞘内注射[Cu]Cu-白蛋白后，在成年和老年小鼠（15-25 个月大）中进行多次时间点的[Cu]Cu-白蛋白 PET。在注射后和稳定期期间定量评估 CSF 清除率和椎旁淋巴结。在初始扰动状态后，通过注射 6 ul（总 CSF 体积的 1/7）来进行下一个稳定期，并且 CSF 从蛛网膜下腔的清除半衰期在成年和老年小鼠中分别为 93.4±19.7 和 123.3±15.6 分钟（p=0.01）。虽然注入 CSF 空间的[Cu]Cu-白蛋白百分比更高，但在第二天，老年小鼠的椎旁淋巴结活性更低。[Cu]Cu-白蛋白 PET 使我们能够定量测量整个脑脊髓水平的 CSF-淋巴引流，并可视化和量化由于 CSF 引流而导致的淋巴结活性。[Cu]Cu-白蛋白 PET 揭示了由于蛛网膜下腔引流减少，老年小鼠 CSF 淋巴引流的年龄相关性下降，尤其是在稳定期。
