Sun Xiaoli, Li Pengcheng, Luo Weihua, Chen Shangbing, Feng Nengyun, Wang Jia, Luo Qingming
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, PR China.
Lasers Surg Med. 2010 Nov;42(9):649-55. doi: 10.1002/lsm.20975.
Cortical spreading depression (CSD) is an important pathological model to study cerebral ischemia and migraine. In pharmacological studies of CSD, dimethylsulfoxide (DMSO) is an efficient solvent for water-insoluble drugs. Previous studies indicated that DMSO could prevent pial arteriolar dilation induced by oxidants. Therefore, it was very important to study the effect of DMSO on hemodynamics during CSD so that optimization of dose of DMSO as solvent can be made.
STUDY DESIGN/MATERIALS AND METHODS: DMSO was topically applied on the exposed rat cortex. Single CSD was elicited by controlled injection of KCl. Pial arteriolar diameter, cerebral blood flow, and direct current potential during CSD were monitored by optical intrinsic signal imaging, laser speckle imaging, and electrophysiology method, respectively.
Topical application of DMSO (0.1%, 0.4%, 2%, and 4%, v/v) increased arteriolar resting diameter and resting blood velocity at all vascular compartments. In addition, both vasodilation and hyperemic response to CSD were attenuated by DMSO in a dose-dependent manner at doses from 0.1% to 4%. In contrast, the maximum value of blood velocity during CSD was not significantly affected by DMSO.
The attenuation in hemodynamic response during CSD could possibly be caused by increased baseline value of vessel tone and blood velocity. Our findings suggest that when investigators use DMSO to dissolve water-insoluble, topically applied drugs in the hemodynamic study of CSD, dose of DMSO should be kept below 0.1% in order to avoid false results.
皮层扩散性抑制（CSD）是研究脑缺血和偏头痛的重要病理模型。在CSD的药理学研究中，二甲基亚砜（DMSO）是一种用于水不溶性药物的有效溶剂。先前的研究表明，DMSO可以预防氧化剂诱导的软脑膜小动脉扩张。因此，研究DMSO对CSD期间血流动力学的影响对于优化DMSO作为溶剂的剂量非常重要。
研究设计/材料与方法：将DMSO局部应用于暴露的大鼠皮层。通过控制性注射氯化钾诱发单次CSD。分别采用光学内在信号成像、激光散斑成像和电生理学方法监测CSD期间软脑膜小动脉直径、脑血流量和直流电位。
局部应用DMSO（0.1%、0.4%、2%和4%，v/v）可增加所有血管段的小动脉静息直径和静息血流速度。此外，在0.1%至4%的剂量范围内，DMSO以剂量依赖的方式减弱了对CSD的血管舒张和充血反应。相比之下，CSD期间血流速度的最大值不受DMSO的显著影响。
CSD期间血流动力学反应的减弱可能是由于血管张力和血流速度的基线值增加所致。我们的研究结果表明，在CSD血流动力学研究中，当研究人员使用DMSO溶解水不溶性局部应用药物时，DMSO的剂量应保持在0.1%以下，以避免出现假结果。
