Download | - View accepted manuscript: Infrared optical imaging of matrix metalloproteinases (MMPs) up regulation following ischemia reperfusion is ameliorated by hypothermia (PDF, 898 KiB)
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DOI | Resolve DOI: https://doi.org/10.1186/1471-2202-13-76 |
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Author | Search for: Barber, Philip A.; Search for: Rushforth, David1; Search for: Agrawal, Smriti; Search for: Tuor, Ursula I.1 |
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Affiliation | - National Research Council of Canada. Medical Devices
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Format | Text, Article |
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Subject | gelatinase 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 |
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Abstract | Background: 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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Publication date | 2012-06-28 |
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In | |
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Language | English |
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Peer reviewed | Yes |
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NPARC number | 21270062 |
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Export citation | Export as RIS |
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Report a correction | Report a correction (opens in a new tab) |
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Record identifier | 9fa3b53b-b728-4b7e-80ad-1f02d9e52199 |
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Record created | 2013-12-18 |
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Record modified | 2020-06-04 |
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