title: Infrared optical imaging of matrix metalloproteinases (MMPs) up regulation following ischemia reperfusion is ameliorated by hypothermia.
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, 1.25 x 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.
authors: Department of Clinical Neurosciences, Experimental Imaging Centre and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Canada. pabarber@ucalgary.ca
authors: Philip A
authors: PA
authors: Barber
authors: David
authors: D
authors: Rushforth
authors: Smriti
authors: S
authors: Agrawal
authors: Ursula I
authors: UI
authors: Tuor
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007839:Functional Laterality; D006979:Hyperthermia, Induced / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D007259:Infrared Rays; D017078:Laser-Doppler Flowmetry; D008297:Male; D045726:Metalloproteases / Q000032:analysis* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015335:Molecular Probes; D015424:Reperfusion; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D015335:Molecular Probes; D045726:Metalloproteases