Department of Anesthesiology, Yale School of Medicine, 330 Cedar Street, New Haven, CT, USA.
Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, USA.
Fluids Barriers CNS. 2021 Jan 6;18(1):1. doi: 10.1186/s12987-020-00236-x.
Large differences in glymphatic system transport-similar in magnitude to those of the sleep/wake cycle-have been observed during anesthesia with dexmedetomidine supplemented with low dose isoflurane (DEXM-I) in comparison to isoflurane (ISO). However, the biophysical and bioenergetic tissue status underlying glymphatic transport differences between anesthetics remains undefined. To further understand biophysical characteristics underlying these differences we investigated volume status across cerebral tissue compartments, water diffusivity, and T2* values in rats anesthetized with DEXM-I in comparison to ISO.
Using a crossover study design, a group of 12 Sprague Dawley female rats underwent repetitive magnetic resonance imaging (MRI) under ISO and DEXM-I. Physiological parameters were continuously measured. MRI included a proton density weighted (PDW) scan to investigate cerebrospinal fluid (CSF) and parenchymal volumetric changes, a multigradient echo scan (MGE) to calculate T2* maps as a measure of 'bioenergetics', and a diffusion scan to quantify the apparent diffusion coefficient (ADC).
The heart rate was lower with DEXM-I in comparison to ISO, but all other physiological variables were similar across scans and groups. The PDW images revealed a 1% parenchymal volume increase with ISO compared to DEXM-I comprising multiple focal tissue areas scattered across the forebrain. In contrast, with DEXM-I the CSF compartment was enlarged by ~ 6% in comparison to ISO at the level of the basal cisterns and peri-arterial conduits which are main CSF influx routes for glymphatic transport. The T2* maps showed brain-wide increases in T2* in ISO compared to DEXM-I rats. Diffusion-weighted images yielded no significant differences in ADCs across the two anesthesia groups.
We demonstrated CSF volume expansion with DEXM-I (in comparison to ISO) and parenchymal (GM) expansion with ISO (in comparison to DEXM-I), which may explain the differences in glymphatic transport. The T2* changes in ISO are suggestive of an increased bioenergetic state associated with excess cellular firing/bursting when compared to DEXM-I.
与异氟醚（ISO）相比，在添加低剂量异氟醚的右美托咪定麻醉（DEXM-I）下观察到神经胶质淋巴系统转运的差异非常大，类似于睡眠/觉醒周期的差异。然而，麻醉下神经胶质淋巴转运差异的生物物理和生物能量组织状态仍未定义。为了进一步了解这些差异背后的生物物理特性，我们研究了在 DEXM-I 与 ISO 麻醉的大鼠中脑内组织容积状态、水扩散系数和 T2*值的差异。
采用交叉研究设计，一组 12 只 Sprague Dawley 雌性大鼠在 ISO 和 DEXM-I 下进行重复磁共振成像（MRI）。连续测量生理参数。MRI 包括质子密度加权（PDW）扫描，以研究脑脊液（CSF）和实质容积变化，多梯度回波扫描（MGE）以计算 T2*图作为“生物能量”的测量指标，以及扩散扫描以量化表观扩散系数（ADC）。
DEXM-I 组的心率低于 ISO 组，但所有其他生理变量在扫描和组间均相似。PDW 图像显示 ISO 下脑实质体积增加 1%，包括散在分布在前脑多个局灶性组织区域。相比之下，DEXM-I 下基底池和动脉周围导管（主要为神经胶质淋巴转运的 CSF 流入途径）的 CSF 容积增加了约 6%，而 ISO 下则增加了 6%。T2图显示 ISO 下大脑的 T2值普遍升高，而 DEXM-I 组大鼠的 T2*值则升高。扩散加权图像显示两种麻醉组之间的 ADC 无显著差异。
我们证明了 DEXM-I 下 CSF 容积扩张（与 ISO 相比）和 ISO 下实质（GM）扩张（与 DEXM-I 相比），这可能解释了神经胶质淋巴转运的差异。与 DEXM-I 相比，ISO 下的 T2*变化表明生物能量状态增加，与细胞过度放电/爆发有关。
