RESUMO
The aim of the present study was to investigate whether ciliary neurotrophic factor (CNTF) plays its neuroprotective role following hypoxic injury through the activation of signal transducer and activator of transcription 3 (STAT3) signaling. Firstly, to determine whether CNTF exerts its effects via STAT3 following hypoxic injury, cultured neurons from the cerebral cortex of mice were prepared and a neuronal model of hypoxia was then established. The neurons exposed to hypoxia were then pre-treated with CNTF and transfected with small interference RNA (siRNA) targeting STAT3 (STAT3 siRNA) using polybrene, or with STAT3Tyr705 mutant or STAT3Ser727 mutant using an electroporation system. The survival, proliferation and neurite outgrowth of the neurons subjected to different treatments were also determined. RT-qPCR and western blot analysis were employed to examine the expression levels of STAT3, p-STAT3Tyr705 and p-STAT3Ser727 following treatment with CNTF and other treatments. Our results revealed that treatment with CNTF: i) protected neurons from hypoxic injury by promoting survival and neurite growth; ii) induced a significant increase in the levels of STAT3, STAT3pTyr705 and the STAT3pTyr705/STAT3 ratio; it did not however, significantly affect the levels of STAT3pSer727 in the hypoxic cerebral cortex neurons. Transfection of the hypoxic neurons pre-treated with CNTF with STAT3 siRNA or STAT3Tyr705 neutralized the protective effects exerted by CNTF. The findings of our study thus demonstrate that CNTF protects neurons from hypoxic injury through the activation of STAT3pTyr705.
Assuntos
Fator Neurotrófico Ciliar/metabolismo , Neurônios/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Animais , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Fator Neurotrófico Ciliar/farmacologia , Códon , Regulação da Expressão Gênica , Inativação Gênica , Camundongos , Mutação , Crescimento Neuronal/efeitos dos fármacos , Crescimento Neuronal/genética , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , RNA Interferente Pequeno/genética , Tirosina/genéticaRESUMO
We aimed to evaluate the association between 25-hydroxyvitamin D [25(OH) D] levels and both clinical severity at admission and outcome at discharge in patients with acute ischemic stroke (AIS). From June 2012 to October 2013, consecutive first-ever AIS patients admitted to the Department of Emergency of The Fourth Affiliated Hospital of Harbin Medical University, China were identified. Clinical information was collected. Serum 25(OH) D levels were measured at baseline. Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS) score. Functional outcome was evaluated at discharge using the modified Rankin scale (m-Rankin). Multivariate analyses were performed using logistic regression models. During the study period, 326 patients were diagnosed as AIS and were included in the analysis. Serum 25(OH) D levels reduced with increasing severity of stroke as defined by the NIHSS score. There was a negative correlation between levels of 25(OH) D and the NIHSS (r = - 0.389, P = 0.000). In multivariate analyses, serum 25(OH) D level was an independent prognostic marker of discharge favorable functional outcome and survival [odds ratio 3.96 (2.85-7.87) and 3.36 (2.12-7.08), respectively, P = 0.000 for both, adjusted for NHISS, other predictors and vascular risk factors] in patients with AIS. Serum 25(OH) D levels are a predictor of both severity at admission and favorable functional outcome in patients with AIS. Additional research is needed on vitamin D supplementation to improve the outcome of post-stroke patients.
Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Vitamina D/sangueRESUMO
OBJECTIVE: To investigate the changes in the content of plasma matrix metallo proteinase-9 (MMP-9) in patients with acute cerebral infarction before and after thrombolytic therapy and its clinical significance. METHODS: The levels of MMP-9 were determined in 34 patients with acute cerebral infarction before and after thrombolytic therapy, and 34 healthy individuals served as healthy control. RESULTS: Compared with the healthy controls, the levels of plasma MMP-9 before thrombolytic therapy were not significantly increased [(13.47±3.09) ng/L vs. (12.89±10.22) ng/L, P >0.05]. In contrast, MMP-9 values were significantly increased after thrombolytic therapy [(22.06±12.53) ng/L] compared with that in either before or healthy control group (both P<0.05). MMP-9 values were significantly higher in patients with hemorrhage after thrombolytic therapy (incidence rate was 26.5%, 9/34) compared with before treatment [(24.02±15.41) ng/L vs. (14.28±2.33) ng/L, P<0.05], and the values of MMP-9 were higher than those of patients without hemorrhage [(20.42±9.57) ng/L], but there was no statistically significant difference ( P >0.05). In patients with complete revascularization (revascularization rate was 58.8%, 20/34), MMP-9 level was markedly higher than before thrombolytic therapy after thrombolytic therapy [(19.26±7.94) ng/L vs. (13.63±3.02) ng/L, P<0.05], and the values of MMP-9 were higher than the no-revascularization patients [(18.97±4.23) ng/L], but there was no statistically significant difference ( P >0.05). CONCLUSION: Thrombolytic therapy activated MMP-9, and MMP-9 increased the risk of hemorrhage after thrombolytic therapy, and it participated in the mechanisms of hemorrhagic tendency after thrombolysis.
