In vivo two-photon fluorescence microscopy reveals disturbed cerebral capillary blood flow and increased susceptibility to ischemic insults in diabetic mice.
In vivo two-photon fluorescence microscopy reveals disturbed cerebral capillary blood flow and increased susceptibility to ischemic insults in diabetic mice.
复制标题
DOI：
10.1111/cns.12268
复制
发表时间：
2014-09
影响因子：
5.5
通讯作者：
Han F
中科院分区：
文献类型：
--
作者：
Huang JY;Li LT;Wang H;Liu SS;Lu YM;Liao MH;Tao RR;Hong LJ;Fukunaga K;Chen Z;Wilcox CS;Lai EY;Han F
糖尿病会增加中风的风险，但其机制尚不清楚。本研究在脑中动脉闭塞（MCAO）缺血模型中验证了糖尿病扰乱脑微循环和增加脑损伤易感性的假设。用链脲佐菌素诱导内皮细胞中表达绿色荧光蛋白的小鼠（Tie2-GFP小鼠）发生糖尿病。4周后，进行短暂（20分钟）MCAO。采用双光子激光扫描显微镜（TPLSM）测量脑动脉、静脉和毛细血管的体内血流。TPLSM检测显示，糖尿病小鼠毛细血管中的红细胞（RBC）速度明显下降，但激光多普勒血流仪检测的局部脑血流保持不变。糖尿病小鼠仅在MCAO后出现脑毛细血管湍流。这些小鼠在MCAO后持续增加的神经功能缺陷，伴随着紧密连接蛋白的过度降解和脑组织中CaMKII磷酸化的钝化，表明血脑屏障被破坏和认知潜能受到干扰。糖尿病小鼠更容易受到脑毛细血管血流紊乱的影响，这可能使它们在缺血后容易出现神经血管缺陷。
Diabetes mellitus increases the risk of stroke but the mechanisms are unclear. The present study tested the hypothesis that diabetes mellitus disturbs the brain microcirculation and increases the susceptibility to cerebral damage in a middle cerebral artery occlusion (MCAO) model of ischemia. Diabetes was induced by streptozocin in mice expressing green fluorescent protein in endothelial cells (Tie2-GFP mice). Four weeks later, they were subjected to transient (20 min) MCAO. In vivo blood flow was measured by two-photon laser scanning microscopy (TPLSM) in cerebral arteries, veins and capillaries. There was a significant decrease in red blood cell (RBC) velocity in capillaries in diabetic mice as assessed by TPLSM, yet the regional cerebral blood flow, as assessed by laser-Doppler flowmetry, was maintained. Brain capillary flow developed turbulence after MCAO only in diabetic mice. These mice sustained increased neurological deficits after MCAO which were accompanied by an exaggerated degradation of tight junction proteins and blunted CaMKII phosphorylation in cerebral tissues indicating disruption of the blood brain barrier and disturbed cognitive potential. diabetic mice are more susceptible to disturbances of cerebral capillary blood flow which may predispose them to neurovascular defects following ischemia.
登录
查看更多内容
影响因子：
9.8
作者：
Schaffer CB;Friedman B;Nishimura N;Schroeder LF;Tsai PS;Ebner FF;Lyden PD;Kleinfeld D
通讯作者：
Kleinfeld D
影响因子：
9.8
作者：
Zhang S;Murphy TH
通讯作者：
Murphy TH
DOI：
10.1073/pnas.95.26.15741
发表时间：
1998-12-22
影响因子：
11.1
作者：
Kleinfeld, D;Mitra, PP;Denk, W
通讯作者：
Denk, W
影响因子：
8.2
作者：
Ryan, CM;Geckle, MO;Orchard, TJ
通讯作者：
Orchard, TJ
DOI：
10.1073/pnas.0402937101
发表时间：
2004-07-06
影响因子：
11.1
作者：
Long, DS;Smith, ML;Damiano, ER
通讯作者：
Damiano, ER