Infrared optical imaging of matrix metalloproteinases (MMPs) up regulation following ischemia reperfusion is ameliorated by hypothermia

BMC Neuroscience

Research Article

Smriti Agrawal¹  Philip A Barber²  Ursula I Tuor³  David Rushforth⁴ 

[1] Department of Clinical Neurosciences, Experimental Imaging Centre and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Canada;Department of Clinical Neurosciences, Experimental Imaging Centre and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Canada;Experimental Imaging Centre, B153, 3330 Hospital Dr NW, University of Calgary, T2N 2T9, Calgary, AB, Canada;Department of Clinical Neurosciences, Experimental Imaging Centre and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Canada;IBD West, National Research Council, Canada;Experimental Imaging Centre, B153, 3330 Hospital Dr NW, University of Calgary, T2N 2T9, Calgary, AB, Canada;IBD West, National Research Council, Canada;

关键词: Middle Cerebral Artery Occlusion;    Ischemia Reperfusion;    External Carotid Artery;    Filter Cube;    NIRF Imaging;   

DOI  :  10.1186/1471-2202-13-76

 received in 2012-03-23, accepted in 2012-06-18,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundWe 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.ResultsIncreased 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.ConclusionsMatrix-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.

【 授权许可】

CC BY   
© Barber et al.; licensee BioMed Central Ltd. 2012