Synchron Inc, New York, United States of America.
Department of Biomedical Engineering, The City College of New York, CUNY, New York, United States of America.
J Neural Eng. 2023 Jul 24;20(4). doi: 10.1088/1741-2552/ace4f4.
. Transcranial direct current stimulation (tDCS) generates sustained electric fields in the brain, that may be amplified when crossing capillary walls (across blood-brain barrier, BBB). Electric fields across the BBB may generate fluid flow by electroosmosis. We consider that tDCS may thus enhance interstitial fluid flow.. We developed a modeling pipeline novel in both (1) spanning the mm (head),m (capillary network), and then nm (down to BBB tight junction (TJ)) scales; and (2) coupling electric current flow to fluid current flow across these scales. Electroosmotic coupling was parametrized based on prior measures of fluid flow across isolated BBB layers. Electric field amplification across the BBB in a realistic capillary network was converted to volumetric fluid exchange.. The ultrastructure of the BBB results in peak electric fields (per mA of applied current) of 32-63Vm-1across capillary wall and >1150Vm-1in TJs (contrasted with 0.3Vm-1in parenchyma). Based on an electroosmotic coupling of 1.0 × 10- 5.6 × 10m3s-1m2perVm-1, peak water fluxes across the BBB are 2.44 × 10- 6.94 × 10m3s-1m2, with a peak 1.5 × 10- 5.6 × 10m3min-1m3interstitial water exchange (per mA).. Using this pipeline, the fluid exchange rate per each brain voxel can be predicted for any tDCS dose (electrode montage, current) or anatomy. Under experimentally constrained tissue properties, we predicted tDCS produces a fluid exchange rate comparable to endogenous flow, so doubling fluid exchange with further local flow rate hot spots ('jets'). The validation and implication of such tDCS brain 'flushing' is important to establish.
. 经颅直流电刺激 (tDCS) 在大脑中产生持续的电场，当穿过毛细血管壁（穿过血脑屏障，BBB）时，这些电场可能会被放大。穿过 BBB 的电场可能会通过电渗产生流体流动。我们认为 tDCS 因此可以增强细胞外液的流动。. 我们开发了一种新的建模管道，它（1）跨越毫米（头部）、米（毛细血管网络），然后是纳米（到 BBB 紧密连接（TJ））尺度；（2）将电流流动与这些尺度上的流体流动相耦合。基于对分离 BBB 层的流体流动的先前测量，对电渗偶联进行了参数化。在真实毛细血管网络中穿过 BBB 的电场放大被转换为体积流体交换。. BBB 的超微结构导致毛细血管壁上的峰值电场（每施加 1 mA 电流）为 32-63 Vm-1，而 TJ 中的峰值电场>1150 Vm-1（与 0.3 Vm-1 相比）在实质中）。基于 1.0 × 10- 5.6 × 10m3s-1m2每 Vm-1 的电渗偶联，穿过 BBB 的峰值水通量为 2.44 × 10- 6.94 × 10m3s-1m2，峰值 1.5 × 10- 5.6 × 10m3min-1m3细胞外液交换（每 mA）。. 使用此管道，可以预测任何 tDCS 剂量（电极排列、电流）或解剖结构下每个脑体素的流体交换率。在受实验限制的组织特性下，我们预测 tDCS 产生的流体交换率与内源性流动相当，因此通过进一步的局部流速热点（“射流”）将流体交换率增加一倍。tDCS 大脑“冲洗”的验证和意义很重要。
