title: Mild hypothermia of 34°C reduces side effects of rt-PA treatment after thromboembolic stroke in rats.
abstract: BACKGROUND
  Hypothermia is neuroprotective in experimental stroke and may extend the so far limited therapeutic time window for thrombolysis. Therefore, hypothermia of 34°C and its effects on delayed thrombolysis including reperfusion-associated injury were investigated in a model of thromboembolic stroke (TE).
  
  
  METHODS
  Male Wistar rats (n = 48) were subjected to TE. The following treatment groups were investigated: control group - normothermia (37°C); thrombolysis group - rt-PA 90 min after TE; hypothermia by 34°C applied 1.5 to 5 hours after TE; combination therapy- hypothermia and rt-PA. After 24 hours infarct size, brain edema and neuroscore were assessed. Protein markers for inflammation and adhesion, gelatinase activity, and blood brain barrier (BBB) disruption were determined. MRI-measurements investigated infarct evolution and blood flow parameters.
  
  
  RESULTS
  The infarct volume and brain swelling were smaller in the hypothermia group compared to the other groups (p < 0.05 to p < 0.01). Thrombolysis resulted in larger infarct and brain swelling than all others. Hypothermia in combination with thrombolysis reduced these parameters compared to thrombolysis (p < 0.05). Moreover, the neuroscore improved in the hypothermia group compared to control and thrombolysis. Animals of the combination therapy performed better than after thrombolysis alone (p < 0.05). Lower serum concentration of sICAM-1, and TIMP-1 were shown for hypothermia and combination therapy. Gelatinase activity was decreased by hypothermia in both groups.
  
  
  CONCLUSIONS
  Therapeutic hypothermia reduced side-effects of rt-PA associated treatment and reperfusion in our model of TE.
authors.affiliation: Department of Neurology, University of Erlangen, Germany. rainer.kollmar@uk-erlangen.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kallmünzer
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwab
authors.forename: Rainer
authors.initials: R
authors.lastname: Kollmar