on February 10, 2005
Published online before print February 10, 2005, doi: 10.1161/01.STR.0000155684.20864.58
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Submitted on May 23, 2004
From the Stroke Research Laboratory, Department of Medicine, University of Alberta, Edmonton, AB, Canada. * To whom correspondence should be addressed. E-mail: ashfaq.shuaib{at}ualberta.ca.
Background and Purpose--Previously, we have shown that hyperthermia significantly increased neuronal damage after ischemic injury in a focal embolic model of stroke in rats. In the present study, we examined the effects of hyperthermia on the efficacy of thrombolytic therapy in this stroke model. Methods--In part A, efficacy of tissue plaminogen activator (tPA) treatment was examined in normothermic and hyperthermic rats after embolization of preformed clots into middle cerebral artery (MCA). In part B, brain perfusion deficits were assessed in rats after MCA occlusion. In part C, blood-brain barrier (BBB) permeability was examined in rats after MCA occlusion. In part D, we examined the influence of hyperthermia on fibrinolytic activity of tPA in vitro. Results--Results showed that treatment with tPA significantly reduced infarct volume in normothermic and 38°C hyperthermic rats. When compared with normothermic rats, perfusion deficits in hyperthermic rats were significantly increased at both 3 hours and 6 hours after ischemic injury. Compared with normothermic sham-operated rats, Evans blue dye extravasation was increased in the injured rats with 39°C hyperthermia. In vitro study showed that hyperthermia increased the fibrinolytic activity of tPA. Conclusions--The present study shows that hyperthermia masks the neuroprotective effects of tPA treatment after ischemic injury and that this may be caused by increased BBB permeability, increased edema, and early progression of ischemic penumbral region to irreversibly damaged tissue as shown by progressively increasing perfusion deficits in hyperthermic rats.
Revised on September 21, 2004
Accepted on October 12, 2004
Hyperthermia Masks the Neuroprotective Effects of Tissue Plaminogen Activator
Raza Noor MS;
Key words: hyperthermia • ischemia • middle cerebral artery • perfusion
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