Intracerebral hemorrhage (ICH) has a devastating impact on the neonatal population. Whether thrombocytopenia is sufficient to cause ICH in neonates is still being debated. In this study, we comprehensively investigated the consequences of severe thrombocytopenia on the integrity of the cerebral vasculature by using 2 orthogonal approaches: by studying embryogenesis in the Nfe2-/- mouse line and by using biologics (anti-GP1Bα antibodies) to induce severe thrombocytopenia at defined times during development. By using a mouse model, we acquired data demonstrating that platelets are required throughout fetal development and into neonatal life for maintaining the integrity of the cerebral vasculature to prevent hemorrhage and that the location of cerebral hemorrhage is dependent on when thrombocytopenia occurs during development. Importantly, this study demonstrates that fetal and neonatal thrombocytopenia-associated ICH occurs within regions of the brain which, in humans, could lead to neurologic damage.
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