title: Evaluation of inflammatory response to acute ischemia using near-infrared fluorescent reactive oxygen sensors.
abstract: OBJECTIVE
  Ischemia-related processes associated with the generation of inflammatory molecules such as reactive oxygen species (ROS) are difficult to detect at the acute stage before the physiologic and anatomic evidence of tissue damage is present. Evaluation of the inflammatory and healing response early after an ischemic event in vivo will aid in treatment selection and patient outcomes. We introduce a novel near-infrared hydrocyanine molecular probe for the detection of ROS as a marker of tissue response to ischemia and a precursor to angiogenesis and remodeling. The synthesized molecular probe, initially a non-fluorescent hydrocyanine conjugated to polyethylene glycol, converts to a highly fluorescent cyanine reporter upon oxidation.
  
  
  METHODS
  The probe was applied in a preclinical mouse model for myocardial infarction, where ligation and removal of a portion of the femoral artery in the hindlimb resulted in temporary ischemia followed by angiogenesis and healing.
  
  
  RESULTS
  The observed increase in fluorescence intensity was approximately sixfold over 24 h in the ischemic tissue relative to the uninjured control limb and was attributed to the higher concentration of ROS in the ischemic tissue.
  
  
  CONCLUSIONS
  These results demonstrate the potential for non-invasive sensing for interrogating the inflammatory and healing response in ischemic tissue.
authors: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Selena
authors: S
authors: Magalotti
authors: Tiffany P
authors: TP
authors: Gustafson
authors: Qian
authors: Q
authors: Cao
authors: Dana R
authors: DR
authors: Abendschein
authors: Richard A
authors: RA
authors: Pierce
authors: Mikhail Y
authors: MY
authors: Berezin
authors: Walter J
authors: WJ
authors: Akers
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000175:diagnosis* / Q000473:pathology; D007511:Ischemia / Q000175:diagnosis* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000473:pathology; D017382:Reactive Oxygen Species; D019265:Spectroscopy, Near-Infrared; D014018:Tissue Distribution; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine
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