RESUMO
AIM: 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). MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: Our results indicated that combination treatment of stroke with G-CSF and simvastatin augments the neuroprotective effect in rats after ICH.
Assuntos
Hemorragia Cerebral/tratamento farmacológico , Combinação de Medicamentos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fármacos Neuroprotetores/farmacologia , Sinvastatina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Edema Encefálico/tratamento farmacológico , Modelos Animais de Doenças , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacosRESUMO
Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury.
