RESUMO
Aneurysmal subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease with very poor prognosis. The aim of the present study was to evaluate the protective effects of atorvastatin on early brain injury (EBI) after SAH using a perforation SAH model. Male Sprague-Dawley rats were randomly divided into four groups: the sham group, the SAH group (model group), SAH + 10 mg.kg-1day-1 atorvastatin (low atorvastatin group), and SAH + 20 mg.kg-1day-1 atorvastatin (high atorvastatin group). Atorvastatin was administered orally by gastric gavage for 15 days before operation. At 24 h after SAH, we evaluated the effects of atorvastatin on brain water content, apoptosis by TUNEL assay and scanning electron microscope (SEM), and the expression of apoptosis-related proteins by immunofluorescence and Western blotting analysis. Compared with the sham group, we observed increased brain water content, significant apoptosis, and elevated levels of apoptosis-related proteins including caspase-3, CCAAT enhancer-binding protein homologous protein (CHOP), the 78-kDa glucose-regulated protein (GRP78), and aquaporin-4 (AQP4) in the SAH group. Atorvastatin administration under all doses could significantly reduce brain water content, apoptosis, and the expression levels of caspase-3, CHOP, GRP78, and AQP4 at 24 h after SAH. Our data show that early treatment with atorvastatin effectively ameliorates EBI after SAH through anti-apoptotic effects and the effects might be associated inhibition of caspase-3 and endoplasmic reticulum (ER) stress related proteins CHOP and GRP78.
Assuntos
Anticolesterolemiantes/farmacologia , Apoptose/efeitos dos fármacos , Atorvastatina/farmacologia , Lesões Encefálicas/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Hemorragia Subaracnoídea Traumática/tratamento farmacológico , Administração Oral , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Aquaporina 4/genética , Aquaporina 4/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/genética , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Caspase 3/genética , Caspase 3/metabolismo , Modelos Animais de Doenças , Reposicionamento de Medicamentos , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnoídea Traumática/genética , Hemorragia Subaracnoídea Traumática/metabolismo , Hemorragia Subaracnoídea Traumática/patologia , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Água/análise , Água/metabolismoRESUMO
OBJECTIVE: To investigate the clinical applied anatomy in the region of anterior clinoid process, and to improve the therapeutic efficacy of clinoidal tumors. METHODS: Twelve patients with large meningiomas located in clinoid were surgically treated via the extended anterior and middle fossa combined with epidural approach between January 1998 and August 2004. The surgical outcome and follow-up results were reviewed retrospectively. Supraorbital-posterional approach and cranioorbital zygomatic approach were used when tumors involved cavernous sinus. Anterior clinoid process was grinded with high-speed drilling. Supply of tumors were blocked extradurally. Tumors were resected intradurally. RESULTS: Of the 12 cases in large meningiomas located in clinoid, 8 cases had total removal of tumors, 3 patients had subtotal removal. Of the 10 patients with pre-operative severe visual deterioration, 6 patients was markedly improved, one patient unchanged and one patient worsened post-operatively. No death was found in this group. CONCLUSIONS: Using epidural approach for clinoidal meningiomas and grinding anterior clinoid process was advantageous to block tumors base blood supply and detach infraclinoidal tumors from internal carotid artery. Supraorbital-pterional approach could minimize brain retraction and was advantageous to expose superior pole of giant tumors.