Abstract:
Brain fluid clearance by pathways including the recently described paravascular glymphatic system is a critical homeostatic mechanism by which metabolic products, toxins, and other wastes are removed from the brain. Brain fluid clearance may be especially important after traumatic brain injury (TBI), when blood, neuronal debris, inflammatory cells, and other substances can be released and/or deposited. Using a non-invasive dynamic positron emission tomography (PET) method that models the rate at which an intravenously injected radiolabeled molecule (in this case 11C-flumazenil) is cleared from ventricular cerebrospinal fluid (CSF), we estimated the overall efficiency of brain fluid clearance in humans who had experienced complicated-mild or moderate TBI 3-6 months before neuroimaging (n = 7) as compared to healthy controls (n = 9). While there was no significant difference in ventricular clearance between TBI subjects and controls, there was a significant group difference in dependence of ventricular clearance upon tracer delivery/blood flow to the ventricles. Specifically, in controls, ventricular clearance was highly, linearly dependent upon blood flow to the ventricle, but this relation was disrupted in TBI subjects. When accounting for blood flow and group-specific alterations in blood flow, ventricular clearance was slightly (non-significantly) increased in TBI subjects as compared to controls. Current results contrast with past studies showing reduced glymphatic function after TBI and are consistent with possible differential effects of TBI on glymphatic versus non-glymphatic clearance mechanisms. Further study using multi-modal methods capable of assessing and disentangling blood flow and different aspects of fluid clearance is needed to clarify clearance alterations after TBI.
摘要:
通过包括最近描述的血管旁淋巴系统在内的途径清除脑液是代谢产物的关键稳态机制,毒素,和其他废物从大脑中去除。脑液清除在创伤性脑损伤(TBI)后可能尤其重要,当血液,神经元碎片,炎症细胞,和其他物质可以被释放和/或沉积。使用非侵入性动态正电子发射断层扫描(PET)方法,该方法对静脉注射放射性标记的分子(在本例中为11C-氟马西尼)从脑室脑脊液(CSF)中清除的速率进行建模,我们估计了在神经影像学前3~6个月出现复杂-轻度或中度TBI的人(n=7)与健康对照组(n=9)相比的脑液清除总有效率.虽然TBI受试者和对照组之间的心室清除率没有显着差异,示踪剂输送/流向心室的血流对心室清除率的依赖性存在显着差异。具体来说,在控件中,心室清除率很高,线性依赖于流向心室的血流,但是这种关系在TBI受试者中被破坏了。当考虑血流和特定群体的血流变化时,与对照组相比,TBI受试者的心室清除率略有(非显著)增加.当前的结果与过去的研究形成对比,该研究显示TBI后的淋巴功能降低,并且与TBI对腺淋巴和非腺淋巴清除机制的可能差异作用一致。需要使用能够评估和解开血流和液体清除率的不同方面的多模态方法进行进一步研究,以阐明TBI后的清除率变化。