Investigating the effects of dimethylsulfoxide on hemodynamics during cortical spreading depression by combining laser speckle imaging with optical intrinsic signal imaging.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Sun
Xiaoli
X
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, PR China.
Li
Pengcheng
P
Luo
Weihua
W
Chen
Shangbing
S
Feng
Nengyun
N
Wang
Jia
J
Luo
Qingming
Q
D000287:Administration, Topical; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D013181:Cortical Spreading Depression / Q000187:drug effects; D003451:Cryoprotective Agents / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007834:Lasers; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D003451:Cryoprotective Agents; D004121:Dimethyl Sulfoxide