Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System
Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System
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DOI：
10.1038/s41598-020-59045-9
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发表时间：
2020-02-06
影响因子：
4.6
通讯作者：
Tannenbaum, Allen
中科院分区：
文献类型：
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作者：
Kounda, Sunil;Elkin, Rena;Tannenbaum, Allen
淋巴系统（GS）假说认为，平流驱动的脑脊液（CSF）从血管周围空间流入间质液空间，迅速运输溶质并清除脑内废物。然而，平流在神经膜中的存在是有争议的，并且声称溶质仅通过扩散运输。为了解决这一争议，我们实现了最优质量输运（rOMT）问题的正则化版本，其中平流/扩散方程是唯一需要的先验假设。采用拉格朗日视角对GS传输进行的rOMT分析显示，脑脊液中的溶质速度比灰质和白质更快。此外，rOMT分析还证明了大脑区域溶质速度的2倍差异。综上所述，这些结果表明，在脑脊液中，平流转运占主导地位，而扩散和平流转运都有助于实质中的GS转运。在大鼠脑血管病（cSVD）模型中，与正常大鼠相比，溶质在血管周围空间（PVS）中的转运和PVS到组织的转移速度较慢。因此，rOMT的分析框架为GS转运的局部动力学提供了新的见解，可能对神经退行性疾病有影响。未来的研究应采用rOMT分析方法来证实cSVD患者的GS转运减少。
The glymphatic system (GS) hypothesis states that advective driven cerebrospinal fluid (CSF) influx from the perivascular spaces into the interstitial fluid space rapidly transport solutes and clear waste from brain. However, the presence of advection in neuropil is contested and solutes are claimed to be transported by diffusion only. To address this controversy, we implemented a regularized version of the optimal mass transport (rOMT) problem, wherein the advection/diffusion equation is the only a priori assumption required. rOMT analysis with a Lagrangian perspective of GS transport revealed that solute speed was faster in CSF compared to grey and white matter. Further, rOMT analysis also demonstrated 2-fold differences in regional solute speed within the brain. Collectively, these results imply that advective transport dominates in CSF while diffusion and advection both contribute to GS transport in parenchyma. In a rat model of cerebral small vessel disease (cSVD), solute transport in the perivascular spaces (PVS) and PVS-to-tissue transfer was slower compared to normal rats. Thus, the analytical framework of rOMT provides novel insights in the local dynamics of GS transport that may have implications for neurodegenerative diseases. Future studies should apply the rOMT analysis approach to confirm GS transport reductions in humans with cSVD.