Hyperthermia masks the neuroprotective effects of tissue plaminogen activator.

Abstract:

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 degrees 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 degrees 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.

journal_name

Stroke

journal_title

Stroke

authors

Noor R,Wang CX,Shuaib A

doi

10.1161/01.STR.0000155684.20864.58

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

665-9

issue

3

eissn

0039-2499

issn

1524-4628

pii

01.STR.0000155684.20864.58

journal_volume

36

pub_type

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