Journal of the neurological sciences
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In this study, we investigated the dose-effect relationship and safety of tissue plasminogen activator (tPA) for the treatment of intraventricular hemorrhage/hematoma (IVH) in rats. Adult male Sprague-Dawley rats were injected with autologous blood into the left lateral ventricle to establish IVH. Two hours later, Ringer's saline or 0.25-2 microg of tPA were administered directly to the IVH over 3 h. ⋯ Instead, 1-2 microg of tPA caused additional injuries, including intraventricular leukocytosis and edema of periventricular tissues and choroid plexus on both hemispheres. These results indicate that higher doses of tPA may have detrimental effects on the brain. The dosage rate of 0.5 microg seems beneficial to treat 5 microl of IVH (equals to a dose of 0.1 mg/ml blood) in our model in terms of the satisfactory fibrinolysis and less damage to the brain.