Abstract EN:

Spontaneous intracerebral hemorrhages (ICH) are a severe form of stroke. ICH might be associated with intraventricular hemorrhage (IVH). In a meta-analysis of clinical trials, we have shown that the injection of a fibrinolytic agent within the ventricles improves the outcome of patients with severe IVH. However, the results depend on the fibrinolytic agent used: tissue plasminogen activator (tPA) appeared as not beneficial, whereas Urokinase was. This difference could be due to the neurotoxic properties of tPA, which we investigated then in a murine model of IVH. When comparing both fibrinolytic agents, we found that, unlike Urokinase, tPA increased neuronal death and inflammation, resulting in a neurological outcome worse than after treatment with Urokinase. TPA is noxious by promoting NMDA-mediated glutamatergic neurotransmission. Accordingly, since ICH induces an overexpression of tPA in an intend of hematoma clearance, this endogenous tPA could also have toxic action via its effect on NMDA receptors. We have treated rats suffering from an ICH with an antibody inhibiting the interaction between tPA and NMDA receptors. This strategy decreased neuronal death and inflammation around the hematoma, resulting in a better functional outcome. MRI is the imaging modality of choice for stroke diagnosis, especially to differentiate hemorrhagic and ischemic cases. Many stroke patients are treated by oxygen therapy. But oxygen alters MRI signals. In mice, we found that T2* evidence of ICH disappear under oxygen therapy. This could lead to wrong diagnoses, but we have also shown that this phenomenon might be helpful in improving the sensitivity of PWI or molecular imaging.