Intracranial hemorrhage (ICH) is a devastating disease that induces
hematoma formation with poor neuronal outcome.
Levetiracetam (LEV) has been approval for
epilepsy seizures. In a previous study, LEV exerted protective effects on
cerebral ischemia models; however, the detail effects and the influence of LEV on ICH are still unknown. The aim of this study was to investigate whether
oral administration of LEV (50 or 150 mg/kg) has protective effects on ICH injury using both in vivo and in vitro experiments. In in vivo experiments, we utilized ICH models induced by autologous blood (bICH) or
collagenase (cICH) injection. Moreover, we established a neuronal injury model using SYSH5Y human
neuroblastoma cell lines. In the bICH model, frequently
oral administration of LEV attenuated both
cerebral edema and neurological deficits. In addition, the expression levels of phosphorylation-extracellular signal‑related
kinase (ERK) 1/2 and cleaved
caspase-7 were increased after ICH, and LEV suppressed such alterations. In in vitro experiments,
hematoma releasing factors, such as
hemoglobin (Hb) and
hemin, induced neuronal cell death, and LEV treatment attenuated neuronal injury in a dose-dependent manner. In the cICH model, neurological deficits induced by extensive
hematoma formation were attenuated by LEV without affecting
hematoma volume. Taken together, these findings suggested that LEV has protective effect on neurons after ICH injury. Therefore, LEV may not only be an efficacious therapeutic agent for
seizures, but also for post-
hemorrhagic stroke brain injury.