Division of Bioinformation and Therapeutic Systems, National Defense Medical College Research Institute, Tokorozawa, Saitama, Japan.
Graduate School of Bio-Applications & Systems Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo, Japan.
J Neurosci Res. 2018 May;96(5):875-888. doi: 10.1002/jnr.24201. Epub 2017 Nov 18.
In ischemic stroke research, a better understanding of the pathophysiology and development of neuroprotection methods are crucial, for which in vivo imaging to monitor spreading depolarizations (SDs) and evolution of tissue damage is desired. Since these events are accompanied by cellular morphological changes, light-scattering signals, which are sensitive to cellular and subcellular morphology, can be used for monitoring them. In this study, we performed transcranial imaging of near-infrared (NIR) diffuse reflectance at ∼800 nm, which sensitively reflects light-scattering change, and examined how NIR reflectance is correlated with simultaneously measured cerebral blood flow (CBF) for a rat middle cerebral artery occlusion (MCAO) model. After MCAO, wavelike NIR reflectance changes indicating occurrence of SDs were generated and propagated around the ischemic core for ∼90 min, during which time NIR reflectance increased not only within the ischemic core but also in the peripheral region. The area with increased reflectance expanded with increase in the number of SD occurrences, the correlation coefficient being 0.7686 (n = 5). The area with increased reflectance had become infarcted at 24 hr after MCAO. The infarct region was found to be associated with hypoperfusion or no-flow response to SD, but hyperemia or hypoperfusion followed by hyperemia response to SD was also observed, and the regional heterogeneity seemed to be connected with the rat cerebrovasculature and hence existence/absence of collateral flow. The results suggest that NIR reflectance signals depicted early evolution of tissue damage, which was not seen by CBF changes, and enabled lesion progression monitoring in the present stroke model.
在缺血性中风研究中,更好地了解病理生理学和神经保护方法的发展至关重要,为此,人们希望通过体内成像来监测扩散去极化(SD)和组织损伤的演变。由于这些事件伴随着细胞形态变化,因此可以使用对细胞和亚细胞形态敏感的光散射信号来监测它们。在这项研究中,我们对近红外(NIR)漫反射进行了经颅成像,该方法在∼800nm 处对光散射变化敏感,并检查了 NIR 反射率如何与同时测量的大脑血流(CBF)相关联,以用于大鼠大脑中动脉闭塞(MCAO)模型。MCAO 后,会产生指示 SD 发生的类似波浪的 NIR 反射率变化,并在缺血核心周围传播约 90 分钟,在此期间,NIR 反射率不仅在缺血核心内增加,而且在周围区域也增加。反射率增加的区域随着 SD 发生次数的增加而扩大,相关系数为 0.7686(n=5)。MCAO 后 24 小时,反射率增加的区域已发生梗死。发现增加的反射率区域与 SD 引起的低灌注或无血流反应有关,但也观察到了 SD 引起的充血或低灌注后再充血反应,区域异质性似乎与大鼠脑血管有关,因此存在/不存在侧支血流。结果表明,NIR 反射率信号描绘了组织损伤的早期演变,而 CBF 变化则无法观察到这一点,并且能够在当前中风模型中监测病变进展。