@misc{oai:repo.qst.go.jp:00071366,
 author = {Unekawa, Miyuki and Tomita, Yutaka and Toriumi, Haruki and Osada, Takashi and Masamoto, Kazuto and Kawaguchi, Hiroshi and Itoh, Yoshiaki and Kanno, Iwao and Suzuki, Norihiro and 畝川 美悠紀 and 冨田 裕 and 鳥海 春樹 and 長田 高志 and 正本 和人 and 川口 拓之 and 菅野 巖},
 month = {May},
 note = {Objectives: Cortical spreading depression (CSD), a propagating phenomenon of depolarizing neurons and astroglia, dramatically affects cortical cerebral blood flow (CBF) by still undetermined mechanisms. We previously reported suppression of red blood cell (RBC) velocity flowing in capillaries conversely in the region of neuronal activation (1,2). To further understand the mechanisms of CBF control during CSD, we examined temporal pattern of diametric changes in pial vessels and CBF. 
Methods: To visualize blood vessels, we used Tie2-GFP transgenic mice (N=16), in which specifically vascular endothelial cells emit fluorescence. Under urethane anesthesia and artificial ventilation, a cranial window was installed on the temporo-parietal region of the cerebral cortex. KCl (1 M) was applied on the brain surface through a burr hole posterior to the cranial window to elicit CSD. Diameters of pial arteries, veins and capillaries were measured with the confocal laser-scanning fluorescence microscopy and an image analysis software ImagePro. DC potential was simultaneously recorded next to the window along with CBF by laser Doppler flowmeter. The fluorecent flow in cerebral vessels was recorded on a video after the intravenous bolus injection before and after CSD elicitation. Pixel-by-pixel microflow values (a reciprocal of mean transit time: 1/MTT) were calculated from the temporal intensity change by the in-house Matlab software KEIO-IS1 in the same region of interest (3). 
Results: Application of KCl induced biphasic response, first constriction of pial arteries (-35.4pm18.8%) during DC potential deflection and then dilation (5.2pm12.6%). CBF increased with transient drop observed at the peak time of vasoconstriction.There was no significant correlation between baseline diameters of the pial arteries and their % changes during CSD (r=0.342). Pial veins and capillaries showed small but significant dilation. Second and third waves of CSD also elicited vasodilation but the response was diminished (4.8pm10.9% and 1.9pm7.4%, respectively), whereas CBF increase (29.6pm14.5% and 27.7pm12.0%) without transient drop was repeatedly observed without diminution. Mild vasoconstriction was observed only in limited cases (n=25/40 and 10/30). After CSD, CBF decreased and reached a plateau below the baseline level (-19.7 pm 9.2%) (post-CSD oligemia), whereas 1/MTT decreased only 12.4pm11.6% and became stable with diameter of pial vessels returning to the baseline levels.
Conclusion: Initial increase in CBF during first CSD may be counteracted with vasoconstriction induced through mechanisms different from flow-metabolism coupling. Diametric responses in pial vessels were diminished, whereas increase in CBF was repeatedly observed. Thus, cerebrovascular control in response to CSD might be largely affected by peripheral vessels from the pial artery such as penetrating arteries. Together with our previous reports of suppressed RBC flow (1,2), it is suggested that diameter of pial artery and cortical CBF are controlled differently during CSD.
References: 
(1) Unekawa M et al, Microcirculation, 19:166-74, 2012. 
(2) Unekawa M et al, J Neurosci Res, in press. 
(3) Tomita Y et al, Brain Res, 1372:59-69, 2011., Brain & BrainPET 2013},
 title = {DIFFERENT RESPONSE IN DIAMETER OF PIAL VESSELS AND IN CEREBRAL BLOOD FLOW ASSOCIATED WITH CORTICAL SPREADING DEPRESSION IN ANESTHETIZED MICE},
 year = {2013}
}