Enhanced neuroprotective effects of co-administration of G-CSF with simvastatin on intracerebral hemorrhage in rats

Based on the neuroprotective effect of either G-CSF or statins in various neurological disease models, the purpose of this study was to evaluate the superiority of combined therapy G-CSF with simvastatin in experimental intracerebral hemorrhage (ICH). Primary ICH was induced in male Sprague Dawley rats. G-CSF (50 μg/kg), simvastatin (2 mg/kg), combined G-CSF and simvastatin, or phosphate buffered saline was given at 24 hours post-ICH. Neurobehavioral outcomes were assessed in all rats. The pathological changes of neuronal ultrastructure were examined with transmission electron microscopy at the given time. Simultaneously, immunohistochemical labeling and TUNEL assay were performed. Co-administration of G-CSF with simvastatin significantly promoted functional recovery and expedited the recovery time. Transmission electron microscopy revealed that combination treatment significantly improved ultrastructural outcomes. Histological examination showed that the expressions of Brdu co-labeled with NSE and GFAP, Factor VIII were higher in combined treatment than in control group. Additionally, the number of cell apoptosis was higher in control group than in experimental groups and lowest in combination group. Our results indicated that combination treatment of stroke with G-CSF and simvastatin augments the neuroprotective effect in rats after ICH.