Urokinase versus Alteplase for intraventricular hemorrhage fibrinolysis

作者：Gaberel Thomas^*; Montagne Axel; Lesept Flavie; Gauberti Maxime; Lemarchand Eloise; Orset Cyrille; Goulay Romain; Bertrand Thomas; Emery Evelyne; Vivien Denis

来源：Neuropharmacology, 2014, 85: 158-165.

DOI：10.1016/j.neuropharm.2014.05.001

• Intraventricular
• Cerebral hemorrhage
• Fibrinolytic agents
• Ventriculostomy
• Tissue-type plasminogen activator
• Urokinase-type plasminogen activator
• Animal model

Intraventricular hemorrhage (IVH) is the most severe form of stroke with intraventricular fibrinolysis (IVF) as a hopeful treatment. Urokinase (uPA) and tissue-type plasminogen activator (tPA) are used for IVF in Human. No clinical trial has evaluated the differential impact of these two fibrinolytics for IVF. Thus, we decided here to compare the use of these two fibrinolytics in a pre-clinical study. IVH was induced in rats by injection of collagenase type VII within the brain parenchyma followed by an NE Rats were randomized to receive uPA, tPA or saline within the ventricle, and cerebrospinal fluid was aspirated. Hematoma and ventricular volumes, brain water contents, inflammation and neurological deficits were measured at day three post-treatments. We also performed in vitro studies, in which neuronal cultures were subjected to an excitotoxic paradigm in the presence of either uPA or tPA. In the IVH model, we showed that although both uPA and tPA led to reduced ventricular volumes, only uPA significantly improved functional recovery. These results could be explained by the fact that uPA, in contrast of tPA, fails to promote inflammatory processes and neurotoxicity. Our study provides evidence supporting the use of uPA for fibrinolysis of IVH. A clinical trial could be warranted if tPA failed to improve outcomes in human IVH.

• 出版日期2014-10