Background Continuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear. Methods Dynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visualize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes. Results Based on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimination across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces. Conclusions Collectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases.

中文翻译：

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随着年龄的增长，穿过筛板的脑脊液引流动力学会降低


背景 脑脊液 (CSF) 的持续循环和引流对于消除 CSF 携带的代谢产物和神经元功能至关重要。虽然已经确定了多种脑脊液引流途径，但每种途径对正常引流的重要性以及衰老大脑中脑脊液流出区域是否存在差异变化尚不清楚。方法使用近红外荧光标记白蛋白的动态体内成像来同时可视化中枢神经系统背侧（经颅和脊髓）流出区域的脑脊液流动。随后进行动力学分析，其中包括这些区域的消除速率常数。此外，还评估了示踪剂在离体组织中的分布，包括鼻/筛状区域、脑背侧和腹侧表面、脊髓、硬脑膜、颅底、视神经和三叉神经以及颈部淋巴结。结果根据体内数据，有证据表明，根据清除率确定，脑脊液是从鼻腔途径穿过筛板和脊髓蛛网膜下腔消除的，但不是从背侧硬脑膜区域消除的。使用离体组织样本，证实示踪剂存在于筛状区和嗅觉区、软脑膜血管周围、脊髓蛛网膜下腔、脊髓和颈淋巴结，但不存在于背侧硬脑膜、颅底或其他颅神经。此外，离体组织显示示踪剂沿脑裂和与脑表面池相关的区域保留，但不在脑实质中保留。衰老会减少脑脊液穿过筛板的消除，但不会减少来自脊髓 SAS 的脑脊液清除，也不会减少在大脑表面的保留。 结论 总的来说，这些数据表明，小鼠脑脊液的主要流出部位是穿过筛板的鼻区域和来自脊柱区域的区域。在年轻的成年小鼠中，鼻腔和筛状路径对流出的贡献远高于脊柱区域。在老年小鼠中，鼻途径对脑脊液流出的贡献显着减少，但脊髓途径则没有。这种动力学方法可能对确定神经系统疾病、年龄相关的认知能力下降和脑部疾病中脑脊液引流的早期变化具有重要意义。