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BACKGROUND: Oxidative stress and neurocyte apoptosis are crucial pathophysiological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Geniposide (GNP) has been reported to exert neuroprotective effects by reducing oxidative injury and neurocyte apoptosis. However, the effect of GNP has not been clarified in EBI after SAH. The study was performed to evaluate the neuroprotective effects and mechanisms of GNP in EBI after SAH. METHODS AND RESULTS: A total of 60 male Wistar rats were randomly divided into five groups. The prechiasmatic cistern SAH model was used in this study. SAH grade was evaluated using a grading system. Neurological function was evaluated using the Garcia scores. Brain edema was measured by the wet-dry method. Blood-brain barrier (BBB) permeability was measured by the extravasation of Evans Blue (EB). The neurocyte apoptosis was observed using TUNEL assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutathione S-transferase (GST) and quinone oxidoreductase-1 (NQO-1) were performed. The results showed that GNP reduced brain edema, attenuated BBB permeability, inhibited neurocyte apoptosis and improved neurological function. Moreover, GNP also decreased the levels of ROS and MDA, elevated Nrf2 expression in the temporal cortex and up-regulated the expression of NQO-1, HO-1 and GST after SAH. CONCLUSIONS: GNP could ameliorate oxidative stress and neurocyte apoptosis to exert neuroprotective effects by Nrf2 pathway.
Assuntos
Edema Encefálico , Lesões Encefálicas , Fármacos Neuroprotetores , Hemorragia Subaracnóidea , Animais , Apoptose , Encéfalo/metabolismo , Edema Encefálico/tratamento farmacológico , Edema Encefálico/metabolismo , Glutationa Transferase/metabolismo , Iridoides , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismoRESUMO
PURPOSE: Nontraditional lipid parameters are associated with intracranial atherosclerotic stenosis (ICAS) progression. This study aimed to investigate the association of nontraditional lipid parameters with the risk of restenosis in patients with ICAS after endovascular treatment (EVT). METHODS: This study retrospectively enrolled consecutive patients with symptomatic ICAS after successful EVT followed by at least 3 months of angiography. Participants were divided into restenosis or non-restenosis groups based on the angiographic follow-up results. The nontraditional lipid parameters were calculated from conventional lipid parameters. The COX regression models and restricted cubic splines (RCS) were used to explore the association between nontraditional lipid parameters and restenosis. RESULTS: This study recruited 222 cases with 224 lesions eligible for our study, of which 56 (25%) had restenosis. Compared with the non-restenosis group, patients in the restenosis group had higher levels of the atherogenic index of plasma (AIP) (0.211, interquartile range, IQR, 0.065-0.404 vs. 0.083, IQR, -0.052-0.265, Pâ¯= 0.001), remnant cholesterol (RC) (0.55, IQR, 0.33-0.77 vs. 0.30, IQR, 0.18-0.49, Pâ¯< 0.001) and Castelli's indexI (CRI-I) (4.13, IQR, 3.39-5.34 vs. 3.74, IQR, 2.94-4.81, Pâ¯= 0.030). In the multivariable COX regression analysis, a 0.1 unit increase of AIP was an independent risk factor for restenosis (hazard ratio, HRâ¯= 1.20, 95% confidence interval, CI 1.05-1.35, Pâ¯= 0.005) whereas such an association was not observed for RC (HRâ¯= 1.01, 95% CI 0.90-1.15, Pâ¯= 0.835). The restricted cubic spline (RCS) plot revealed a linear relationship between AIP and restenosis (P for nonlinearâ¯= 0.835) but a nonlinear relationship for RC (P for nonlinearâ¯= 0.012). Patients were stratified according to tertiles (T) of AIP and RC and the risk of restenosis increased in T3 compared to T1 (HRâ¯= 3.21, 95% CI 1.35-7.62, Pâ¯= 0.008 and HRâ¯= 2.99, 95% CI 1.11-8.03, Pâ¯= 0.030, respectively). Furthermore, this association remained stable within each LDLC level subgroup. CONCLUSION: The AIP and RC were positively and independently associated with restenosis in patients with ICAS after EVT.
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BACKGROUND: Drug coated balloon (DCB) angioplasty can provide sustained anti-restenotic efficacy without the limitations of permanent vascular implantation and is presumably ideal for treating intracranial atherosclerotic disease. However, the safety of paclitaxel in the neurovasculature remains a concern. METHODS: 242 patients with angiographically verified symptomatic stenosis >70% in intracranial arteries treated with DCB angioplasty were reviewed divided into two groups: group A, patients with stenotic intracranial arteries; and group B, patients with acute, subacute, or chronic occluded intracranial arteries. The primary endpoint was any stroke or death within 30 days. The secondary endpoint was arterial restenosis of >50% during follow-up. RESULTS: 16 major and 12 minor complications occurred among 245 procedures (6.5% and 4.9%, respectively). Five patients died within 30 days after the procedure (2.1%, 5/242). 12 major and 12 minor complications occurred among 211 procedures in group A (5.7% and 5.7%). In group B, four major complications occurred among 34 procedures (11.8%). Hyperperfusion and perforator stroke accounted for half of all complications (53.6%, 15/28). Restenosis >50% was present in eight lesions during the follow-up period (4.8%, 8/167). CONCLUSIONS: After treatment with DCB angioplasty, complications were no different from those after standard balloon angioplasty or stenting. This study suggests that DCB angioplasty may be a safe and effective procedure for intracranial arterial stenosis.
Assuntos
Angioplastia com Balão , Arteriosclerose Intracraniana , Doença Arterial Periférica , Acidente Vascular Cerebral , Humanos , Constrição Patológica , Resultado do Tratamento , Doença Arterial Periférica/cirurgia , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/cirurgia , Materiais Revestidos Biocompatíveis , Artéria Femoral , Artéria Poplítea/cirurgia , Grau de Desobstrução VascularRESUMO
BACKGROUND: Although percutaneous transluminal angioplasty and stenting (PTAS) was an effective and safe alternative treatment for severe intracranial atherosclerosis disease (ICAD), the high rate of restenosis remained a major issue for this endovascular procedure. Recently, the application of drug-coated balloons (DCB) in ICAD was developed to reduce restenosis. This systematic review aimed to evaluate the efficacy and safety of DCB angioplasty for ICAD. METHODS: We searched relevant databases for eligible studies enrolling ICAD patients treated with DCB. The event rates of restenosis and periprocedural complications in the follow-up period were pooled with random-/fixed-effect models using Freeman-Tukey double arcsine transformation. Heterogeneity tests and publication bias tests were performed. RESULTS: Two hundred and twenty-four ICAD patients treated with DCB from 9 eligible studies were included. Rate of stenosis in the DCB arm before treatment was ranged from 62% to 90% and reported median follow-up was ranged from 3 to 10.7 months. The pooled incidence of restenosis were 5.7% (95% confidence interval [CI] 2.6%-9.7%; I2 = 0%, p = 0.516) and 5.9% for periprocedural complications (95% CI: 2.5-10.3%; I2 = 0%, p = 0.649) in follow-up term. CONCLUSION: With the limitation of the low quality of the available evidence, angioplasty with DCB appears to be effective and safe in severe ICAD. Further larger randomized trials are needed to provide more definitive evidence and to address the ideal clinical context for their application.
Assuntos
Angioplastia com Balão , Arteriosclerose Intracraniana , Angioplastia , Angioplastia com Balão/métodos , Materiais Revestidos Biocompatíveis/uso terapêutico , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Humanos , Arteriosclerose Intracraniana/etiologia , Arteriosclerose Intracraniana/cirurgia , Resultado do TratamentoRESUMO
The Wnt signaling pathway is necessary for the development of the central nervous system and is associated with tumorigenesis in various cancers. However, the mechanism of the Wnt signaling pathway in glioma cells has yet to be elucidated. Small-molecule Wnt modulators such as ICG-001 and AZD2858 were used to inhibit and stimulate the Wnt/ß-catenin signaling pathway. Techniques including cell proliferation assay, colony formation assay, Matrigel cell invasion assay, cell cycle assay and Genechip microarray were used. Gene Ontology Enrichment Analysis and Gene Set Enrichment Analysis have enriched many biological processes and signaling pathways. Both the inhibiting and stimulating Wnt/ß-catenin signaling pathways could influence the cell cycle, moreover, reduce the proliferation and survival of U87 glioma cells. However, Affymetrix expression microarray indicated that biological processes and networks of signaling pathways between stimulating and inhibiting the Wnt/ß-catenin signaling pathway largely differ. We propose that Wnt/ß-catenin signaling pathway might prove to be a valuable therapeutic target for glioma.