RESUMO
The aim of the present study was to examine the neuroprotective effect of Qingnao dripping pills (QNDP), especially the infiltration of neutrophils and macrophages, as well as the mitogen-activated protein kinase (MAPK) signal pathway. Adult male Sprague-Dawley rats were randomized to three groups: sham, MCAO, and QNDP. After 24 h of ischemia and reperfusion, neurological deficit scores and infarct volume were measured. Macrophages and neutrophil infiltration in the ischemic brain were respectively determined with CD68 and MPO immunofluorescence and western blot. The proteins involved in MAPK signaling (SAPK/JNK, P-SAPK/JNK, p38, P-p38, ERK1/2, and P-ERK1/2) were measured by western blotting. In vitro ischemic paradigm (oxygen-glucose deprivation) was performed in SH-SY5Y cells to evaluate the effects of QNDP. The viability and death ration of cells induced OGD/R was measured by MTT and LDH assay. The proteins involved in MAPK signaling were measured by western blotting. The results showed that QNDP treatment significantly improved the neurological deficit scores and reduced infarct size. In addition, QNDP treatment inhibited the number of CD68- and MPO-positive cells in the ischemic brain. It inhibited the MAPK signaling pathway in the ischemic brain and SH- SY5Y cells induced OGD/R.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Western Blotting , Isquemia Encefálica/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/patologiaRESUMO
BACKGROUND Autophagy is characterized by the degradation of cellular components in autophagosomes. It plays a significant role in cerebral ischemic injury and has a complex functional connection with apoptosis. The neurovascular unit (NVU) is a structural and functional unit of the nervous system presented as a therapeutic target of stroke. This study aimed to investigate the effect of autophagy induced by ischemic damage on NVUs. MATERIAL AND METHODS SH-SY5Y cells, C6 cells, and rat brain microvascular endothelial cells were cultured with oxygen-glucose deprivation (OGD) exposure for different time durations, and 3-methyladenine (3-MA) was added as an autophagy inhibitor. In all 3 cell lines, lactate dehydrogenase (LDH) release was measured. Furthermore, apoptosis was detected using Annexin V-fluorescein isothiocyanate/propidium iodide labeling and immunofluorescence staining. Autophagosomes were observed through AO/MDC (acridine orange/monodansycadaverine) double staining. LC3-II expression levels were evaluated by western blot analysis. RESULTS In the OGD groups of 3 cell lines, LDH leakage, and apoptotic rates were obviously increased. Remarkable increase in LC3-II expression was found in the OGD groups of SH-SY5Y cells and C6 cells. However, 3-MA decreased the LC3-II expression to varying degrees. CONCLUSIONS OGD could induce the over-activation of autophagy and augment the apoptotic activity in neurons and glial cells of NVUs.
Assuntos
Hipóxia-Isquemia Encefálica/metabolismo , Acoplamento Neurovascular/efeitos dos fármacos , Acoplamento Neurovascular/fisiologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Células Endoteliais/metabolismo , Glucose/metabolismo , Humanos , Miócitos de Músculo Liso/metabolismo , Neurônios/metabolismo , Oxigênio/metabolismo , RatosRESUMO
OBJECTIVE: To overview the methodological quality, report quality and evidence quality of the systematic review (SR) of acupuncture for vascular cognitive impairment ( VCI ). METHODS: The SRs regarding acupuncture for VCI were searched in PubMed, Cochrane Library, EMbase, CNKI, SinoMed, Wanfang and VIP databases. The retrieval period was from the establishment of the database to September 24, 2020. The report quality, methodological quality and evidence quality of the included SRs were evaluated by PRISMA statement, the AMSTAR 2 tool and the GRADE system. RESULTS: A total of 22 SRs were included, including 102 outcome indexes. The methodological quality was generally low, with low scores on items 2, 5, 7, 10, 14, 15 and 16. The report quality was good, with scores ranging from 19 points to 24.5 points. The problems of report quality were mainly reflected in the aspects of structural abstract, program and registration, other analysis and funding sources. The level of outcome indexes of SRs was mostly low or very low, and the main leading factor was limitation, followed by inconsistency and inaccuracy. CONCLUSION: Acupuncture for VCI is supported by low quality evidence of evidence-based medicine, but the methodological quality and evidence body quality of relevant SRs are poor, and the standardization is needed to be improved.
Assuntos
Terapia por Acupuntura , Disfunção Cognitiva , Disfunção Cognitiva/terapia , Bases de Dados Factuais , Humanos , Relatório de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating disease, its mortality and disability rate are high. In China, hypertensive intracerebral hemorrhage (HICH) is responsible for 75% of all the cases of primary ICH. A lot of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for treating HICH have been carried out. However, these RCTs have a lot of problems, such as heterogeneous outcomes, non-uniform point of measurement. These lead to systematic review/meta-analysis only can include a small number of studies. And outcome measures did not take the wishes of patients and other stakeholders into account. The aim of this study is to establish the core outcome set (COS) for future TCM clinical trials of HICH. METHODS AND ANALYSIS: First, we will develop a long list of general outcomes by making systematic literature review and semi-structured interviews. Then healthcare professionals and patients with HICH will be invited to participate in two rounds of the Delphi survey to determine the importance of the outcome. Finally, a face-to-face consensus meeting will be conducted to determine the final COS of HICH, including what outcomes should be measured and when and how to measure the outcomes. RESULTS: We aim to develop a COS that includes TCM core syndrome for HICH to determine what outcomes should be reported and when and how to measure them. CONCLUSION: By doing this, we can increase the reporting consistency and reduce the reporting bias in the outcome, which leads to the reuse of research data in meta-analysis and the making of informed healthcare decisions. ETHICS AND DISSEMINATION: The entire project has received approval from the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences. The final COS will be published and reported at the national and international conferences. TRIAL REGISTRATION: This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1475 . Registered on December 2019.
Assuntos
Hemorragia Intracraniana Hipertensiva , Medicina Tradicional Chinesa , Técnica Delphi , Humanos , Hemorragia Intracraniana Hipertensiva/diagnóstico , Hemorragia Intracraniana Hipertensiva/tratamento farmacológico , Medicina Tradicional Chinesa/efeitos adversos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Avaliação de Resultados em Cuidados de Saúde/métodos , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
The existing problems in the outcomes of randomized controlled trials (RCTs) of acupuncture for vascular cognitive impairment (VCI) during recent five years are analyzed and suggestions are proposed. The RCTs of acupuncture for VCI were selected in PubMed, EMbase, Cochrane Library, Clinical Trials, CNKI database, Wanfang database, VIP database, SinoMed database and Chinese Clinical Trial Registry (ChiCTR) from January 1, 2015 to September 14, 2020. The outcomes were extracted and analyzed. As a result, 21 RCTs were included and the outcomes used were divided into 9 categories: clinical symptom/sign indexes, quality of life indexes, neuroimaging indexes, neuroelectrophysiology indexes, blood biochemical indexes, hemorheology indexes, TCM syndrome score indexes, clinical efficacy indexes, and safety indexes. Among them, the top three of the most used outcomes were clinical symptoms/signs indexes (21, 100.0%), clinical efficacy indexes (14, 66.7%) and quality of life indexes (12, 57.1%). In the RCTs of acupuncture for VCI, attention should be paid to distinguish the primary outcomes and secondary outcomes, adopt objective and standardized efficacy evaluation, and give consideration to report the outcomes of safety, health economic and TCM characteristic indexes.
Assuntos
Terapia por Acupuntura , Disfunção Cognitiva , Disfunção Cognitiva/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze the current status of clinical trial registration of Traditional Chinese Medicine (TCM) for the treatment of neurological diseases. METHODS: Interventional clinical trials of TCM treatment for ischemic stroke, hemorrhagic stroke, vascular cognitive impairment, tension-type headache before September 22, 2020 on the platform of Chinese Clinical Trial Registry (ChiCTR), and ClinicalTrials.gov were searched. Two researchers independently selected the literature and extracted data. RESULTS: A total of 180 interventional clinical trials were included for analysis. Out of 180 trials, 127 were from ChiCTR and 53 from ClinicalTrials.gov. The countries primary sponsoring the included trials were China (176, 97.8%), and the common categories of primary sponsors were hospital (131, 72.8%). Among the study design, the largest proportion of allocation was randomized (172, 95.6%), interventional model assignment was parallel (163, 90.6%), masking was double blind 49 (27.2%), and the sample size was ≤ 400 (144, 80.0%). The trials were most carried out at a single center (102, 56.7%). Among the included studies, 112 (62.2%) registered on ChiCTR attached the ethical approval documents. In terms of trial stages, 50 (27.7%) studies were in phase IV. The mostly used intervention was Chinese herbal medicines (99, 55%), acupuncture (68, 37.8%) was the second. By searching the registration number on China National Knowledge Infrastructure Database and PubMed, 38 (21.1%) registered trials were published, including 25 protocol studies and 14 research results with one (NCT02275949) published both the protocol and the results. CONCLUSIONS: Irregular and inadequate reporting, untimely update and publication, insufficient information on traditional medicine unique characteristics, and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases. More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.
Assuntos
Terapia por Acupuntura , Acupuntura , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Projetos de PesquisaRESUMO
BACKGROUND: Ginkgo biloba extract (EGb) is widely used to treat impairments in memory, cognition, activities of daily living, inflammation, edema, stroke, Alzheimer's dementia, and aging. AIM: We aimed to evaluate the safety and efficacy of EGb in treating vascular cognitive impairment (VCI). METHODS: The systematic review was performed using the latest guidelines. We searched for EGb-related trials up to March 1, 2021, in four Chinese databases, three English databases, and clinical trial registry platforms. Randomized controlled trials (RCTs) were included if the study enrolled participants with VCI. Two reviewers independently extracted the data and critically appraised the study quality. Heterogeneity was quantified with I 2. Both sensitivity and subgroup analyses were used to identify the sources of heterogeneity. Publication bias was assessed with funnel plots. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate the evidence quality. Outcomes included assessments using the Activities of Daily Living (ADL), Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Hasegawa Dementia Scale (HDS), Barthel Index (BI), Functional Activity Questionnaire (FAQ), and adverse events. RESULTS: In this study, a total of 2019 patients in 23 RCTs were included. EGb appeared to be more effective than control conditions as assessed by the results of cognitive function evaluation, including MMSE (MDMMSE,EGb vs.blank = 3.04, 95% CI: 0.10-5.98; MDMMSE,EGb vs.drugs for VCI = 2.70, 95% CI: 1.39-4.01; MDMMSE,EGb+drugs for VCI vs.blank = 5.90, 95% CI: 4.21-7.59; and MDMMSE,EGb+drugs for VCI vs.drugs for VCI = 3.14, 95% CI: 2.14-4.15), MoCA (MDMoCA,EGb vs.blank = 5.30, 95% CI: 2.15-8.46; MDMoCA,EGb+drugs for VCI vs.blank = 2.66, 95% CI: 1.82-3.50; and MDMoCA,EGb+drugs for VCI vs.drugs for VCI = 2.56, 95% CI: 1.85-3.27), HDS (MDHDS,EGb vs.blank = 6.50; 95% CI: 4.86-8.14; MDHDS,EGb+drugs for VCI vs.drugs for VCI = 3.60, 95% CI: 2.50-4.70), ADL (MDADL,EGb vs.blank = 7.20, 95% CI: 3.28-11.12; MDADL,EGb+drugs for VCI vs.blank = 10.00, 95% CI: 7.51-12.49; and MDADL,EGb+drugs for VCI vs.drugs for VCI = 9.20, 95% CI: 7.26-11.14), BI (MDBI,EGb+drugs for VCI vs.drugs for VCI = 5.71, 95% CI: 2.99-8.43; MDFAQ,EGb vs.drugs for VCI = -1.43, 95% CI: -2.78 to 0.08), and FAQ (MDFAQ,EGb+drugs for VCI vs.drugs for VCI = -2.17, 95% CI: -4.13 to 0.21). Evidence of certainty ranged from medium certainty to very low certainty. CONCLUSION: This meta-analysis showed that EGb may be an effective and safe treatment in improving MMSE, MOCA, ADL, and BI for VCI patients within three months of diagnosis. However, given the quality of the included RCTs, more preregistered trials are needed that explicitly examine the efficacy of EGb. This systematic review has been registered on PROSPERO, with the registration number CRD42021232967.
Assuntos
Disfunção Cognitiva/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Ginkgo biloba , Humanos , Extratos Vegetais/farmacologiaRESUMO
Ischemic stroke patients suffer from relatively limited treatment options. Studies have shown that in cerebral ischemia, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key mediator in mediating inflammatory responses and results in activation of apoptosis signaling pathways. Here we assessed the in vivo and in vitro effects of Qingnao Dripping Pills (QNDP), a traditional Chinese prescription, on inflammatory responses and apoptosis. Our results showed that QNDP could significantly decrease cerebral ischemia injury, improve neurological function and inhibit apoptosis in rats impaired by middle cerebral artery occlusion (MCAO). Further, we found that QNDP inhibited NLRP3 inflammasome expression both in MCAO rats and in SH-SY5Y cells under OGD. Moreover, the levels of inflammatory cytokines including interleukin-1ß (IL-1ß) and IL-18, which mediated by NLRP3 inflammasome and increased in MCAO rats, could be reduced by QNDP, suggesting that QNDP could protect the neurons against inflammation through a mechanism mediated by NLRP3 inflammasome. Nuclear factor-kappa B (NF-κB) was also involved in the anti-inflammatory effect of QNDP. In conclusion, QNDP had neuroprotective effects against cerebral ischemia via inhibiting NLRP3 inflammasome signaling pathway, and was a potential candidate for the future treatment of ischemic stroke.
RESUMO
AIM: Kudiezi injection (KDZ) can improve the clinical outcomes of patients with stroke, but the mechanisms remain unclear. This study aimed to investigate whether KDZ could modulate the nuclear factor kappa B (NF-κB) pathways in rat models of transient middle cerebral artery occlusion (tMCAO). MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to tMCAO and randomized to Sham (sham-operated), tMCAO (tMCAO+0.9% saline), and KDZ (tMCAO+7.2mL/kg KDZ) groups. The infarct volume, brain water content, and neurological deficit were assessed 72h after reperfusion. Immunofluorescence was used to detect the expression of cleaved caspase-3 and NF-κBp65. The expression of cleaved caspase-3, NF-κB p65, TLR4, MyD88, TRAF6, and p-IκBα/IκBα was determined using Western blotting. The expression levels of TNF-α, interleukin (IL)-1ß, and IL-10 in the ischemic cortex were measured using the enzyme-linked immunosorbent assay. In vitro ischemic paradigm (oxygen-glucose deprivation) was performed in SH-SY5Y cells to evaluate the effects of KDZ. KEY FINDINGS: Lower brain water content, smaller infarct volume, and better neurologic function were found in the KDZ group compared with the tMCAO group. The expression of activated caspase-3, TLR-4, TRAF6, NF-κBp65, and p-IκBα/IκBα reduced and the levels of TNF-α and IL-1ß decreased in the KDZ group, with the increased IL-10 level. In SH-SY5Y cells, KDZ significantly reduced the expression of p-IκBα and IκBα, lowered the death ratio, and reversed the effects induced by caffeic acid phenethyl ester (a potent NF-κB inhibitor). SIGNIFICANCE: KDZ may function through downregulating the TLR-4-dependent NF-κB signaling pathway to protect the brain against ischemic injury.