Infrared optical imaging of matrix metalloproteinases (MMPs) up regulation following ischemia reperfusion is ameliorated by hypothermia.
Infrared optical imaging of matrix metalloproteinases (MMPs) up regulation following ischemia reperfusion is ameliorated by hypothermia.
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DOI：
10.1186/1471-2202-13-76
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发表时间：
2012-06-28
期刊：
影响因子：
2.4
通讯作者：
Tuor UI
中科院分区：
文献类型：
--
作者：
Barber PA;Rushforth D;Agrawal S;Tuor UI
我们研究了一种新的MMP可激活探针MMPSense™750 FAST （MMPSense750）用于缺血性卒中早期MMP活性的体内可视化。大脑中动脉闭塞（MCAO）后行光学成像。使用Olympus荧光显微镜、1.25倍物镜、CCD相机和合适的滤光片，分别在749 nm和775 nm处检测激活探针的激发峰和发射峰，获得MMPSense激活后的近红外荧光图像。在注射MMPSense750前和注射后3小时，在同侧和对侧皮质再灌注后2或24小时开始获得图像。注射MMPSense750后，在缺血性损伤的同侧观察到强度增加，但在假动物中没有。在缺血再灌注早期15分钟和缺血后24小时0时（P <0.05），两组的同侧和对侧差异均有统计学意义（P <0.05），并持续到180分钟（P <0.01），但假手术后无统计学意义。同侧信号强度的增加因低温而减弱。这些观察结果与缺血再灌注后5和24小时总MMP-9蛋白水平显著升高（P <0.05）以及低温降低相对应。基质金属蛋白酶在缺血再灌注过程中的上调可以通过MMPSense750在体内快速成像。低温降低了MMPSense750后的光学强度增加和MMP-9蛋白表达的增加，这支持了使用MMPSense的NIRF成像可用于评估卒中治疗的潜在治疗策略的概念。
We investigated the use of a new MMP activatable probe MMPSense™ 750 FAST (MMPSense750) for in-vivo visualization of early MMP activity in ischemic stroke. Following middle cerebral artery occlusion (MCAO) optical imaging was performed. Near-infrared (NIR) fluorescent images of MMPSense activation were acquired using an Olympus fluorescent microscope, 1.25x objective, a CCD camera and an appropriate filter cube for detecting the activated probe with peak excitation and emission at 749 and 775 nm, respectively. Images were acquired starting at 2 or 24 hours after reperfusion over the ipsilateral and contralateral cortex before and for 3 hours after, MMPSense750 was injected. Increased intensities ipsilaterally were observed following MMPSense750 injection with ischemic injury but not in sham animals. There were significant ipsilateral and contralateral differences at 15 minutes (P <0.05) in early ischemic reperfusion and at time 0 in 24 hours post ischemia (P <0.05) which persisted at 180 minutes in both these groups (P <0.01), but not following sham surgery. The increase in ipsilateral signal intensity was attenuated by hypothermia. These observations corresponded with a significant increase in the total MMP-9 protein levels, 5 and 24 hours following ischemia reperfusion (P <0.05) and their reduction by hypothermia. Matrix-metalloproteinase upregulation in ischemia reperfusion can be imaged acutely in-vivo with NIRF using MMPSense750. Hypothermia attenuated both the optical increase in intensity after MMPSense750 and the increase in MMP-9 protein expression supporting the proof of concept that NIRF imaging using MMPSense can be used to assess potential therapeutic strategies for stroke treatment.
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影响因子：
4.1
作者：
Lee, JE;Yoon, YJ;Yenari, MA
通讯作者：
Yenari, MA
DOI：
10.1152/ajpheart.01206.2010
发表时间：
2011-07-01
影响因子：
4.8
作者：
Pires, Paulo W.;Rogers, Curt T.;Dorrance, Anne M.
通讯作者：
Dorrance, Anne M.
影响因子：
6.3
作者：
Yang, Yi;Estrada, Eduardo Y.;Rosenberg, Gary A.
通讯作者：
Rosenberg, Gary A.
影响因子：
8.3
作者：
Barber, PA;Hoyte, L;Buchan, AM
通讯作者：
Buchan, AM
MMP-9，脑缺血治疗的潜在靶点
影响因子：
5.3
作者：
Dong X;Song YN;Liu WG;Guo XL
通讯作者：
Guo XL