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Objective:To investigate any anti-aging effect of repeated transcranial magnetic stimulation (rTMS) and explore the relationship between the effect and relief of clinical symptoms in patients with Parkinson′s disease (PD).Methods:A total of 108 PD patients were randomly divided into an rTMS group and a control group, each of 54, while another 54 healthy counterparts were selected to form a normal group. In addition to anti-PD drug therapy, the rTMS group was given daily rTMS treatment, 5 days a week for 4 weeks, while the control group received sham rTMS treatment, with no treatment of the normal group. Before the treatment and after 4 weeks of treatment as well as and 1 month after the ending of the treatment, the subjects′ clinical exercise symptoms were evaluated using the Unified Parkinson′s Disease Rating Scale (UPDRS), a timed exercise test and the 10m re-entry exercise test. Non-exercise symptoms were assessed using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and the Mini-mental State Examination (MMSE). Fasting venous blood samples were analyzed to quantify the serum levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1β (IL-1β) and matrix metalloproteinase-3 (MMP-3).Results:Four weeks and 1 month after the treatment, the average UPDRS scores, exercise test times and 10m re-entry exercise test results of the rTMS group were significantly better than those before treatment and significantly better than those of the control group at the same time point. The rTMS group′s average HAMA, HAMD and MMSE scores, as well as its average P300 latency and amplitude were also significantly better than those of the control group at the same time point and significantly better than those before treatment. After 4 weeks, the average MMP-3 content in the rTMS group was significantly lower than the control group′s average, and after a month the average levels of TNF, IL-6, IL-1β and MMP-3 of the rTMS group were all significantly different from those before treatment and those of the control group. The TNF, IL-6, IL-1β and MMP-3 levels were all positively correlated with the average UPDRS total score.Conclusion:High-frequency rTMS therapy can change the phenotypes related to cell senescence, and thus has good therapeutic effect on motor and non-motor symptoms of PD.
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As an important cause of ischemic stroke, atrial fibrillation is closely associated with left atrial abnormality. However, the relationship between left atrium, left atrial appendage and ischemic stroke in patients with nonvalvular atrial fibrillation is still controversial. This review focuses on the relationship between the size, shape and function of the left atrium and left atrial appendage and the occurrence, classification, severity and prognosis of ischemic stroke in patients with ischemic stroke accompanied by atrial fibrillation, in order to better recognize and prevent atrial fibrillation-related stroke and evaluate the prognosis of atrial fibrillation-related stroke in clinical practice.
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Objective:In recent years, circular RNAs (circRNAs) related to stroke has been widely studied, and its change involves multiple pathophysiological aspects of stroke, including angiogenesis, neural plasticity, cell apoptosis, and neuroinflammation. Further exploration of the changes of specific circRNAs after acute ischemic stroke and the molecular biological mechanisms involved will help to develop possible new drug targets and improve the prognosis of patients. This article reviews the main circRNAs that have changed after acute ischemic stroke, and their mechanism of action, functional detection methods, and challenges faced by the current research.
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Tirofiban is a selective non-peptide glycoprotein Ⅱb/Ⅲa receptor inhibitor that reversibly inhibits fibrinogen-dependent platelet aggregation and subsequent thrombosis. Thrombosis caused by platelet activation plays a vital role in the occurrence and development of ischemic cerebrovascular events. Some studies have evaluated the use of tirofiban in intravenous thrombolysis and endovascular therapy. Although the optimal dose, conditions of use, and target patients have not been fully identified, the good tolerability of tirofiban and its efficacy in improving recanalization and long-term functional outcomes have been validated. This article reviews the mechanism of tirofiban and its application in the treatment of acute ischemic stroke reperfusion.
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Acute ischemic stroke is the most common type of stroke.At present,intravenous thrombolysis within 4.5 h after onset is still the most effective treatment method.Other reperfusion therapies such as endovascular thrombectomy are also shown to be safe and effective.However,some patients will have reocclusion and it is associated with poor outcome.This article reviews the mechanism and possible measures of prevention and treatment for restenosis after thrombolysis.
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Infection is one of the common complications of stroke. It can seriously affect the prognosis of patients. Poststroke infection is closely associated with immune system imbalance, while the excessive activation of sympathetic nerve is an important factor of the occurrence of immunosuppression after stroke. The sympathetic nerve regulates immune cels primarily via β2 adrenergic receptors on the surface of the immune cels. There is evidence to show that β2 adrenergic receptor mediated immune function enhances rather than inhibits under certain conditions, but its specific molecular mechanism is unclear. This article reviews the molecular mechanisms of β2 adrenergic signaling pathway in regulation of inflammation after stroke.
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Objective To investigate the correlation of large artery stenosis and early neurological deterioration (END) of middle cerebral artery infarction.Methods The patients with middle cerebral artery infarction were enrolled retrospectively.END was defined as that the National Institutes of Health Stroke Scale (NIHSS) scores increased ≥2 within 72 hours of admission compared with the baseline value.Middle cerebral artery and internal carotid artery were evaluated by using cerebral angiography.The degree of stenosis was divided into 4 grades:non-or mild (＜ 50％),moderate (50-70％),severe (71-99％) stenosis,and occlusion (100％).The clinical risk factors,degree of neurological deficits,size of lesion,and major arterial lesions were compared between the END group and the non-END group.Results A total of 256 patients with middle cerebral artery infarction were enrolled,and END occurred in 70 of them (27.34％).The age (P =0.045),infarct volume (P =0.045),baseline NIHSS score (P=0.007),and major arterial stenosis (P =0.038) of the END positive group were significantly higher or lager than those of the END negative group.Multivariate logistic regression analysis showed that the higher baseline NIHSS score (odds ratio [OR] 1.071,95％ confidence interval [CI] 1.004-1.142; P =0.037),infarction diameter ＞ 20 mm (OR 2.077,95％ CI 1.077-3.736; P =0.028),and severe stenosis of the major artery (OR 2.521,95％ CI 1.079-5.886; P=0.033) or occlusion (OR 3.074,95％ CI1.262-7.489; P=0.013) were the independent predictor of END.Conclusions Severe stenosis or occlusion of the major artery may be an independent predictor of END in patients with middle cerebral artery infarction.
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Objective To determine the occurrence and baseline predictive factors of early neurological deterioration ( END) among mild ischemic stroke patients.Methods Mild ischemic stroke patients admitted in the hospital were prospectively enrolled.Univariate and multivariate Logistic recession analyses were used to analyze the demographic data, risk factors of ischemic stroke, clinical, brain imaging and laboratory data.Risk factors of END were identified.Results From June 2012 to August 2013, a total of 319 patients with mild ischemic stroke were enrolled, 45 patients (14.1%) of them experienced END.Univariate analysis showed that baseline NIHSS ( U=3522.000,P=0.000), baseline systolic blood pressure (t=2.871,P=0.004), proportion of symptomatic large artery severe stenosis or occlusion (χ2 =52.564,P=0.000) and proportion of large artery atherosclerosis among TOAST subtypes (χ2 =47.287,P=0.000) in END group were significantly higher than those in non-END group. Multivariate logistic regression analysis showed that baseline systolic blood pressure>142 mmHg (1 mmHg=0.133 kPa) (OR=3.954, 95%CI:1.693-9.236, P=0.001), symptomatic large artery severe stenosis or occlusion (OR=3.170, 95%CI:1.170-8.583, P=0.023) and baseline NIHSS (OR=2.038, 95%CI:1.359-3.057, P=0.001) were associated with END.Conclusions About 14.1% of the mild ischemic stroke patients can occur END.Baseline systolic blood pressure>142 mmHg, symptomatic large artery severe stenosis or occlusion and higher baseline NIHSS were the independent risk factors of END.
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Objective Toinvestigatetherelatedriskfactorsofneurologicaldeterioration(ND)in patientswithacutecerebralinfarction.Methods Atotalof446patientswithacutecerebral infarction admitted to the Department of Neurology,Zhongda Hospital,Southeast University from January 2012 to December 2013 were analyzed retrospectively. ND was defined as the reevaluation of the National Institutes of Health Stroke Scale (NIHSS)scores at any time for the increased admission baseline score 2 (ND2)or 4 (ND4)within the first 72 hours. All subjects were divided into a ND2 group (n=107)and a non-ND2 group (n=339)or a ND4 group (n=62)and a non-ND4 group (n=384 ). The differences of general demography,vascular risk factors,imaging,and hematological dataamongthedifferentgroupswerecompared.Results Ofthe446patients,107cases(24.0%) were diagnosed as ND2 and 62 cases (13. 9%)were diagnosed as ND4. The result of univariate analysis showed that there were significant differences in the length of hospital stay,age,baseline NIHSS score,baseline systolic blood pressure on admission,guilty artery occlusion,and the levels of leukocyte,fasting glucose,and C-reactive protein between the ND2 patients and the non-ND2 patients (all P<0. 05). There were significant differences in sex,age,atrial fibrillation,baseline NIHSS score, baseline systolic blood pressure on admission,guilty artery occlusion,and the level of C-reactive protein between the ND4 patients and the non-ND4 patients (all P<0. 05). After adjustment for the confounding factors,the results of Logistic regression analysis showed that the baseline NIHSS score (OR,1.114, 95%CI 1. 0481-1.185,P=0. 001),C-reactive protein (OR,1. 014,95%CI 1. 004-1. 024,P=0. 004), and guilty artery occlusion (OR,2. 303,95%CI 1. 152-4. 606,P=0. 018)were independently correlated with ND2;while the age (OR,1. 040,95%CI 1. 011-1. 070,P=0. 006),systolic blood pressure (OR, 1.015,95%CI 1. 003-1. 027,P=0. 018),C-reactive protein (OR,1. 016,95%CI 1. 005-1. 026,P=0.003),and guilty artery occlusion (OR,2. 845,95%CI 1. 291-2. 269,P =0. 009)were independently correlatedwithND4.Conclusion TheearlyonsetofNDinpatientswithacutecerebralinfarctionare closely associated with age,stroke severity,baseline systolic blood pressure,C-reactive protein,and occlusion of guilty artery. In the clinical diagnosis and treatment,detecting the above indicators timely may contribute to identify the patients with acute cerebral infarction and early progressive deterioration.
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Objective To investigate the functional outcome in patients with mild ischemic stroke and to identify its risk factors for poor outcome.Methods The patients with mild ischemic stroke treated within 72 hours after onset were enrolled prospectively.According to modified Rankin Scale (mRS) scores at day 90 after onset,the patients were randomly divided into either a poor outcome group (mRS score ＞2) or a good outcome group (mRS scores 0-2).Univariate analysis and multivariate logistic regression analysis were used to compare and analyze the demographic data,vascular risk factors,clinical data,laboratory data,imaging data,and follow-up data.The risk factors for poor outcome in patients with mild ischemic stroke were identified.Results A total of 253 patients with mild ischemic stroke were enrolled,and 71 of them (28.1％) had poor outcome.Univariate regression analysis showed that the patients' proportions of age (t =2.037,P =0.043),baseline National Institutes of Health Stroke Scale (NIHSS) score (U =4 610.000,P =0.000),baseline mRS score (U =5 723.000,P =0.000),as well as previous history of ischemic stroke (x2 =4.950,P =0.026),severe symptomatic artery stenosis or occlusion (x2 =49.037,P =0.000),large artery atherosclerotic stroke (x2 =34.359,P =0.000),early neurologic deterioration (x2 =45.804,P =0.000),complicated by pneumonia (x2 =12.121,P =0.000) and recurrent ischemic stroke (x2 =14.305,P =0.000) of the poor outcome group were significantly higher than those of the good outcome group.Multivariate logistic regression analysis showed that advanced age (odds ratio [OR] 1.049,95％ confidence interval [CI] 1.012-1.086; P =0.008),higher baseline mRS score (OR,2.130,95％ CI 1.212-3.743;P=0.009),higher baseline NIHSS score (OR 1.532,95％ CI 1.064-2.206; P=0.022),severe symptomatic large artery stenosis or occlusion (OR 7.569,95％ CI 3.497-16.380; P=0.000),early neurological deterioration (OR 7.369,95％ CI 2.648-20.510; P =0.000) and recurrent ischemic stroke (OR 10.450,95％ CI 3.071-35.564; P =0.000) were the independent risk factors for poor outcome.Conclusions More than one fourth of the patients with mild ischemic stroke had poor outcome.Advanced age,higher baseline mRS score,higher baseline NIHSS score,severe symptomatic large artery stenosis or occlusion,early neurological deterioration,and recurrent ischemic stroke were the independent risk factors for poor outcome.
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Objective To investigate the early risk factors for stroke-associated pneumonia (SAP) in acute stroke patients with dysphagia.Methods The modified Mann assessment of swallowing ability (MMASA) was used to screen dysphagia in patients with acute stroke admitted to hospital within 24 hours after symptom onset.The patients with dysphagia were used as research subjects.They were divided into either a SAP group or a non-SAP group according to whether they had SAP or not within one week of symptom onset.Univariate and multivariate logistic recession analyses were used to analyze the data of demography,past history,clinical practice,and laboratory.The early risk factors for the occurrence of SAP in patients with dysphagia were identified.The independent risk factors were analyzed with receiver operating characteristic (ROC) curves in order to assess their predictive value for SAP.Results Of the 113 patients with acute stroke,55 had dysphagia,and 30 of them (54.54％ ) had SAP.Univariate analysis showed that the National Institutes of Health Stroke Scale (NIHSS) score (median,[ interquartile range] 16,[ 13 - 21 ] vs.3,[ 1 - 7 ] ; P =0.000),neut rophil counts ([ 8.22 ± 3.75 ] × 109/L vs.[ 5.39 ± 2.56 ] × 109/L; t =3.198; P =0.002),proportion of hemorrhagic stroke (96.00％ vs.4.00％ ;x2 =7.333; P =0.007),and proportion of mechanical ventilation (20.00％ vs. 0.00％;x2=5.612; P=0.018) in the SAP group (n=30) were significantly higher than those in the non-SAP group (n =25),while the MMASA score (median,[ interquartile range ] 53,[ 27 - 84 ] vs.88,[ 66 - 92 ] ; P =0.002),Glasgow Coma sCale (GCS) score (median,[ interquartile range] 10,[7-13] vs.15,[11-15];P=0.001),lymphocytecounts([1.17±0.54] ×109/L vs.[1.75±0.81 ] × 109/L; t =-3.563,P =0.001),CD3+ T lymphocyte counts ([0.73 ± 0.42] × 109/L vs.[ 1.14 ±0.85] × 109/L; t=-2.307; P=0.025),and CD4+ T lymphocyte counts ([0.38± 0.22] × 109/L vs.[ 0.69 ±0.57] × 109/L; t =-2.761; P =0.008) were significantly lower than those in the non-SAP group.Multivariate logistic regression analysis showed that the NIHSS score was higher at admission (odds ratio [ OR ],1.206,95％ confidence interval [ CI ] 1.076- 1.351; P=0.001) and the CD4+ T lymphocyte counts decreased ( OR,0.974,95％ CI 0.952 - 0.997; P =0.025) were the independent risk factors for SAP in stroke patients with dysphagia.The NIHSS score ≥ 10.5 had good predictive value for SAP,and its sensitivity and specificity were 86.7％ and 72.0％ respectively (P =0.000).Conclusions More than half of the acute stroke patients with dysphagia occurred SAP.The NIHSS score at admission,neutrophil counts,stroke types,mechanical ventilation,MMASA score,GCS score,lymphocyte counts,CD3+ T lymphocyte counts,CD4+ Tlymphocyte counts,and other factors were associated with occurrenee of SAP in patients with dysphagia,in which a higher NIHSS score and a decreased CD4+ T lymphocyte counts were independent risk factors for the occurrence of SAP in stroke patients with dysphagia.The NIHSS score ≥ 10.5 at admission had higher predictive value.
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Objective To investigate the value of T cell subsets predicting stroke-associated infection (SAI) in patients with acute ischemic stroke.Methods The consecutive patients with acute ischemic stroke within 36 hours after symptom onset were included.The peripheral venous blood samples were collected the next morning after admission.A flow cytometry was used to detect T cell subsets.The patients were divided into either an infected group or a non-infected group according to whether they had infection or not in hospital within 2 weeks.The information of the risk factors for ischemic stroke was collected,and the relationship between SAI and related risk factors was analyzed.Results A total of 55 patients with acute ischemic stroke were included,28 of them were in the infected group and 27 were in the non-infected group.The percentages of CD3 +T cells (63.42 ± 8.84％ vs.69.55 ± 10.05％ ; P =0.022) and CD4+ T cells (35.34 ± 7.10％ vs,40.46 ±7.24％; P =0.014),and CD4+/CD8+ ratio (1.23 ±0.38 vs.1.55 ±0.56; P =0.023) in the infected group were significantly lower than those in the non-infected group.The multiple regression analysis showed that the higher NIHSS score (odds ratio [ OR] 1.295,95％ confidence interval [ CI] 1.084 - 1.574; P =0.004) and t he decreased percent age of CD4+ T cells (OR 0.874,95 ％ CI 0.784 - 0.974,P =0.015) were the independent predicting factors for SA1.The percentage of CD4+ T cells ＜ 70.35％ had the best predictive value for the occurrence of SAI (sensitivity 77.8％ and specificity 92.3％).Conclusions The decreased proportion of the auxiliary T cells after the onset of acute ischemic stroke may increase the susceptibility of SAI.The detection of T cell subsets may predict the SAI in a certain degree.
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Objective To investigate the relationship between the changes of peripheral cellular immune function and the spleen weight index and the spleen histopathological changes following cerebral ischemiareperfusion in rats.Methods A model of middle cerebral artery occlusion (MCAO) of adult male rats was induced.The peripheral blood cytokine levels,spleen weight index and the spleen histopathological changes were evaluated.Results The serum proinflammatory cytokine interleukin (IL) -1β and interferon (INF) -γ levels in rats increased at 6 and 12 hours respectively after modeling.They began to decrease at 24 hours and decreased to the lowest at 72 hours.Compared to the sham operation group,there were significant differences (P ＜ 0.01 );on the contrary,the anti-inflammatory cytokine IL-10 level decreased at 6 hours after modeling It began to increase at 12 hours and reached the peak at 72 hours.Compared to the sham operation group,there were significant differences (P＜0.01).The spleen weight index in a MCAO group decreased significantly at 6 hours after modeling(P＜0.01) and it began to increase at 12 hours,but it was still lower than that in the sham operation group (P＜0.01),and then it decreased gradually and decreased to the lowest at 72 hours (P＜0.01).HE staining showed that the spleen germinal centers of rats reduced significantly at 72 hours after MCAO and the contours did not show very clear.The correlation analysis showed that the proinflammatory cytokine IL-1 β(r =0.304,P =0.002) and INF-γ (r =0.644,P =0.000) levels were positive correlated with the spleen weight index,and the anti-inflammatory cytokine IL-10 level was negatively correlated with the spleen weight index (r =0.492,P =0.000).Conclusions The rat peripheral cellular immune function after MCAO was in an inhibitory state.The changes of spleen may play an important role in the process of immunosuppression after stroke.
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Patients with acute stroke are easily complicated with infection.It may seriously affect the prognosis.With the constantly in-depth study of the pathogenesis of stroke-related infections,its associated risk factors also become increasingly clear,including stroke severity,stroke types and location,malnutrition,diabetes,dysphagia,disturbance of consciousness,invasive operation,and the use of antacid,etc.This article reviews the major risk factors for stroke-related infections.
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The incidence of dysphagia after stroke is high.It may affect the rehabilitation of patients and increase mortality.The assessment is of great significance for early objective examination of dysphagia,in which the bedside screening tests are the most common assessment methods in the routine clinical work.This article reviews the advances in research on the commonly used bedside screening tests of dysphagia.
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Objective To investigate the learning and memory functions,expression changes of disintegrin and metalloprotease 10 (ADAM10) mRNA in hippocampus in the aged rats with chronic cerebral hypoperfusion as well as the effect of atorvastatin on them.Methods A total of 72 rats were randomly divided into sham operation,cerebral hypoperfusion and atorvastatin treatment groups.A permanent bilateral common carotid artery occlusion (2VO)model was induced.Atorvastatin 10 mg/(kg · d) was administered orally after procedure in the atorvastatin treatment group.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of ADAM10 mRNA in bilateral hippoocampus at 1,2,4,and 16 weeks after modeling,Results Two weeks after modeling,the learning and memory functions were decreased significantly in the cerebral hypoperfusion group compared to the sham operation group (P ＜ 0.05).At 4 and 16 weeks after modeling,they were further decreased (P ＜0.01); there were no significant differences in the learning and memory functions at 1,2,and 3 weeks after modeling between the atorvastatin treatment group and the cerebral hypoperfusion group,however,they were improved significantly at 16 weeks compared to the cerebral hypoperfusion group (P＜0.01).The expression of ADAM10 mRNA in hippocampus at different time points after modeling in the cerebral hypoperfusion group was down-regulated by 22％,43％,35％,and 50％,respectively compared to the sham operation group (all P ＜0.05).The expression of ADAM 10 mRNA in hippocampus at 2 weeks in the atorvastatin treatment group was higher than 22％ in the cerebral hypoperfusion group (P＜0.05).There were not significant differences at other time points.Conelusions Chronic cerebral hypoperfusion results in the down-regulation of the expression of ADAM10 mRNA in hippocampus in the aged rats,and atorvastatin may inhibit down-regulation of the expression of ADAM10 mRNA at early stage.
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Objective To investigate the relationship between the changes of the sympathetic nervous system activity and the peripheral cellular immunodepression after cerebral infarction.Methods An adult male Sprague-Dawley rat model of middle cerebral artery occlusion (MCAO)was induced.A double-antibody sandwich enzyme-linked immunosorbent assay was used to detect the levels of serum proinflammatory cytokines interleukin(IL)-1β,interferon-γ (INF-γ)and anti-inflamatory cytokines IL-10.A competitive enzyme-linked immunosorbent assay was used to detect the levels of serum metanephrine(MN)and normetanephrine(NMN).After blocking sympathetic activity by injecting β -blocker propranolol intraperitoneally,the sympathetic activity and the levels of pro/anti-inflammatory cytokines were detected.Results The levels of serum MN and NMN at 6 hours after MCAO began to increase in the cerebral infarction group compared with the sham operation group.They reached the peak at 72 hours,and then decreased slowly.However,they were still higher than those in the sham operation group 2 weeks after MCAO(P ＜ 0.01 ).At 72 hours after MCAO,the levels of MN and NMN in the propranolol intervention group were decreased significantly(P ＜0.01 ),the levels of proinflammatory cytokines IL-1β and INF-γwere increased significantly(P ＜0.01 ),and the levels of anti-inflammatory cytokine IL-10 were decreased significantly(P ＜0.01).Conclusions When sympathetic nervous system is overactivated after cerebral infarction in rats,the peripheral cellular immunity is in a state of depression;the peripheral immunodepression will be fundamentally reversed after blocking the sympathetic function,and this suggests that the overactivation of sympathetic nervous system may play a important role in the process of immunodepression after cerebral infarction.
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Objective To investigate the effects of Puerarin on the expression of hyperphosphorylated-tau (P_ ser404-tau) and choline acetyltransferase (ChAT) in hippocampus of Alzheimer's disease(AD) rats.Methods The rats were divided into sham-operation group, AD group and Puerarin treated group at randomly. The AD rat models were established by injecting amyloid-beta peptide(A?_ 25-35) into right amygdala. The sham-operation rats were injected with trifluoroacetic acid in the same location. The spatial memory function was observed by Y-maze. The protein expression of P_ ser404-tau and ChAT in hippocampus were detected by immunohistochemistry.Results (1)Compared with sham-operation group,the results of maze test were down in AD group and the number of P_ ser404-tau positive cells was significantly higher,while the number of ChAT positive cells was significantly lower (all P
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Objective To investigate the risk factors of death in patients with acute stroke in the neurological intensive care unit(NICU). Methods The clinical data of 137 patients with acute stroke in the NICU were induced. The risk factors were analysed by univariate and multi-variate Logistic regression analysis.Results There were 13 risk factors including age, coma, hyperpyrexia, pulmonary disease, atrial fibrilation/cardiac dilatation, stroke history, mechanical ventilation, brain midline shift, initial serum glucose, APACHEⅡscores, feeding tube, urethral catheter and concurrent pulmonary infection which had statistical significance between the death group and survive group,by univariate analysis(P