title: Early insulin glycemic control combined with tPA thrombolysis reduces acute brain tissue damages in a focal embolic stroke model of diabetic rats.
abstract: OBJECTIVE
  Therapeutic effects of early insulin glycemic control for poststroke hyperglycemia in combination with tissue-type plasminogen activator (tPA) thrombolytic therapy have not yet been studied but are of great clinical interest. In this study, we tested the effects of insulin plus tPA combination in a model of focal embolic stroke in Type I diabetic rats.
  
  
  METHODS
  Streptozotocin was used to produce Type I diabetes in male Wistar rats for 6 weeks and then embolic focal strokes were induced. All rats were treated with insulin or saline at 1 hour followed by tPA or saline at 1.5 hour after stroke. Mortality, infarction, hemispheric swelling, hemorrhagic transformation, and perfusion defects were examined at 24 hours after stroke. Total plasma plasminogen activator inhibitor-1 antigen and activity levels were measured before stroke and 1.5, 3, and 6 hours after stroke by ELISA.
  
  
  RESULTS
  Early insulin glycemic control alone or tPA thrombolysis alone had no significant effects on ischemic infarction. However, early insulin glycemic control combined with tPA significantly reduced brain infarction and swelling, ameliorated tPA-associated hemorrhagic transformation, and improved plasma perfusion at 24 hours after stroke. We also found that the combination significantly decreased plasma plasminogen activator inhibitor-1 antigen level at 6 hours and plasminogen activator inhibitor-1 activity at 1.5 and 6 hours after stroke.
  
  
  CONCLUSIONS
  Early insulin glycemic control may be beneficial in combination with tPA thrombolysis for ischemic stroke with diabetes mellitus or poststroke hyperglycemia.
authors.affiliation: Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 2411A, Charlestown, MA 02129, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Fan
authors.forename: Mingming
authors.initials: M
authors.lastname: Ning
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D038321:Glycemic Index / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010959:Tissue Plasminogen Activator