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Plasminogen activators potentiate thrombin-induced brain injury
B E Figueroa1, R F Keep, A L Betz
1Department of Surgery, University of Michigan, Ann Arbor 48109-0532, USA.
Stroke
|June 17, 1998
Summary
Thrombolytics like tPA and uPA may worsen brain edema after intracerebral hemorrhage by amplifying thrombin's effects. This suggests caution when using these drugs to treat blood clots in the brain.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Cerebral edema after intracerebral hemorrhage (ICH) is linked to mass effect and thrombin-induced neurotoxicity.
- Thrombolytic agents can interfere with endogenous thrombin inhibitors in the brain.
Purpose of the Study:
- To investigate the impact of intracerebral infusion of tissue plasminogen activator (tPA) and urokinase (uPA) on brain edema.
- To assess the combined effects of these thrombolytics with thrombin.
Main Methods:
- Stereotactic infusion of various solutions into the basal ganglia of adult male rats.
- Measurement of brain water, sodium, and potassium content 24 hours post-infusion.
Main Results:
- Independent infusion of tPA or uPA did not cause significant edema.
- Concomitant infusion with thrombin potentiated thrombin-induced brain injury, increasing water, sodium, and potassium content.
- Combined tPA and thrombin significantly increased animal mortality compared to individual treatments.
Conclusions:
- Plasminogen activators (tPA, uPA) may amplify thrombin-induced brain edema by inhibiting natural thrombin inhibitors.
- Use of tPA or uPA in ICH may exacerbate surrounding tissue edema.