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

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Journal titleBMC Neuroscience
Article number76
Subjectgelatinase B; brain cortex; brain ischemia; brain surgery; enzyme activity; fluorescence microscopy; hypothermia; image processing; in vivo study; infrared radiation; middle cerebral artery occlusion; reperfusion injury; Cerebral Cortex; Enzyme-Linked Immunosorbent Assay; Functional Laterality; Infarction, Middle Cerebral Artery; Infrared Rays; Laser-Doppler Flowmetry; Metalloproteases; Molecular Probes; Up-Regulation
AbstractBackground: 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.Results: 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.Conclusions: 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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AffiliationMedical Devices; National Research Council Canada
Peer reviewedYes
NPARC number21270062
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Record identifier9fa3b53b-b728-4b7e-80ad-1f02d9e52199
Record created2013-12-18
Record modified2016-05-09
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