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Open Access Highly Accessed Research

Mild hypothermia of 34°C reduces side effects of rt-PA treatment after thromboembolic stroke in rats

Bernd Kallmünzer, Stefan Schwab and Rainer Kollmar*

Author Affiliations

Department of Neurology, University of Erlangen, Germany

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Experimental & Translational Stroke Medicine 2012, 4:3  doi:10.1186/2040-7378-4-3

Published: 7 March 2012

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.

Keywords:
focal ischemia; stroke; thrombolysis; hypothermia; reperfusion; MRI; thromboembolic model; rat