1.Neuroprotective effect of PTEN inhibitor BPV on cerebral ischemia-reperfusion injury in rats and its mechanism
Lunlin MAO ; Donglin HAO ; Xiaowei MAO ; Tingting HUANG ; Bona WU
International Journal of Cerebrovascular Diseases 2015;(9):691-698
Objective To investigated the neuroprotective effect of PTEN inhibitor BPV on cerebral ischemia-reperfusion injury in rats and its mechanism. Methods Male Sprague-Dawley rats were used to induce a reperfusion model of middle cerebral artery occlusion for 1 h. During the reperfusion, the BPV solution (0. 2 mg/kg daily) or the equal volume of saline was injected intraperitonealy immediately. The neurological deficit scores were conducted at day 1, 3,5, and 7 after ischemia-reperfusion. At day 4, triphenyl tetrazolium chloride staining was used to assess cerebral infarction volume. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin 10 (IL-10) and tumor necrosis factor α(TNF-α) in cortical ischemic border zones. Real-time quantitative polymerase chain reaction was used to detect the expression level of PTEN mRNA. Western blotting was used to detect the expression levels of PI3K, Akt, and p-GSK-3β. At day 7, Bielschowsky silver staining was used to detect the axonal distribution in the ischemic border zone of the striatum. Immunohistochemical staining was used to detect the expression of myelin basic protein (MBP). Results At day 4 after ischemia-reperfusion, the infarct volume (32. 27% ± 1. 71% vs. 45. 49% ± 2. 12% ; P < 0. 001), TNF-α concentration in the cortical ischemic border zones (134. 17 ± 10. 38 pg/ml vs. 264. 17 ± 24. 84 pg/ml; P < ), and PTEN mRNA level (1. 19 ± 0. 08 vs. 2. 50 ± 0. 06; P < 0. 001) in the rats of the BPV group were al significantly lower than those of the normal saline group. The IL-10 concentration (186. 83 ± 10. 83 pg/ml vs. 147. 83 ± 11. 62 pg/ml; P < 0. 001), and the expression levels of PI3K (0. 43 ± 0. 08 vs. 0. 26 ± 0. 06; P = 0. 004), Akt (0. 52 ± 0. 05 vs. 0. 40 ± 0. 04;P = 0. 001), and p-GSK-3β (0. 75 ± 0. 08 vs. 0. 38 ± 0. 06; P < 0. 001) were al significantly higher than those of the normal saline group. At day 7 after ischemia-reperfusion, the neurological deficit score (4. 83 ± 0. 41 vs. 6. 33 ± 0. 52; P < 0. 001) in the rats of the BPV group was significantly lower than that of the normal saline group. The axon densities in the ischemic border zones (35. 51% ± 2. 45% vs. 25. 31% ± 2. 79% ; P < 0. 001) and the expression level of MBP (32. 56% ± 3. 46% vs. 27. 81% ± 4. 18% ; P = 0. 037) were significantly higher than those of the normal saline group. Conclusions BPV has neuroprotective effect for cerebral ischemia-reperfusion injury in rats. Its mechanism may be associated with the up-regulation of PTEN downstream proteins PI3K, Akt and p-GSK-3β expression to regulate inflammatory mediators and reduce the inflammatory response.
2.Effect of combined clopidogrel-aspirin treatment for acute cerebral ischemic infarction on a correlation between cerebral microbleeds and hemorrhagic transformation
Donglin HAO ; Bona WU ; Jing WU ; Lunlin MAO ; Lihui WANG ; Jin ZHANG
Chinese Journal of Geriatrics 2017;36(4):391-394
Objective To investigate effects of combined clopidogrel-aspirin treatment for acute cerebral ischemie infarction on a correlation between cerebral microbleeds (CMBs)and hemorrhagic transformation(HT),so as to provide a new evidence for acute phase treatment of ischemic stroke with CMBs.Methods One hundred and forty-eighty patients with acute cerebral infarction meeting the inclusion criteria were consecutively admitted to our hospitals.All patients underwent susceptibility weighted imaging(SWI) to detect CMBs.Patients were classed into two groups:with and without CMBs and subdivided into brain lobe group,deep group and mixed group.The influence of CMBs or not and CMBs different positions on the post-infarction HT was compared.Logistic regression analysis was used to assess the relationship between HT and the related risk factors.Results The 142 patients finally were included in the study,with 64 patients without CMBs and 78 with CMBs.The detection rates of CMBs were 54.9%.Hypertensive prevalence rate(x2 =6.96,P =0.010)and the levels of uric acid (t =2.04,P =0.040) were higher in CMBs group than group without CMBs.The incidence rate of HT was 12.5 % (8 cases)in no CMBs group,and 21.8%(17 cases)in the CMBs group(x2 =2.09,P=0.150).6 in 15 patients(40.0%)patients experienced HT in lobar CMBs group;6 patients (12.5 %)experienced HT in 48 patients with deep CMBs group;5 patients(33.3%)experienced HT in 15 patients with mixed CMBs group.There was statistically significant difference in HT incidence rate(x2 =6.52,P=0.038)among the 3 groups.Lobar CMBs are more vulnerable for HT.Logistic regression analysis showed that atrial fibrillation(OR=6.48,95 % CI:2.45-17.19,P =0.000) and hyperglycemia (OR =1.02,95 % CI:1.43 1.94,P =0.020) were risk factors for HT,instead of CMBs(OR=1.95,95%CI:0.78-4.87,P=0.150).Conclusions CMBs do not increase the risk of hemorrhage transformation in cerebral ischemic infarction patients at acute stage with combined antithrombotic treatment.While,the double antithrombotic treatment used in patients with the lobar CMBs should be careful.
3.Relationship between obstructive sleep apnea-hypopnea syndrome and symptomatic carotid stenosis in patients with ischemic cerebrovascular disease
Bona WU ; Xiaonan CHEN ; Dengyue ZHAI ; Maogang CHEN ; Wenhua LIU ; Ning WEI ; Gelin XU ; Xinfeng LIU
International Journal of Cerebrovascular Diseases 2010;18(11):808-812
Objective To investigate the relationship between obstructive sleep apneahypopnea syndrome (OSAHS) and carotid stenosis in patients with ischemic cerebrovascular disease (ICVD) and to provide reference for developing the intervention strategy of carotid stenosis. Methods Eighty-seven patients with ICVD were screened from Nanjing Stroke Registry Program. The patients were divided into without (n=21), mild(n=24), moderate (n=27) and severe (n = 11) OSAHS groups according to the apnea-hypopnea index (AHI); in addition, the patients were divided into with (n =34) and without carotid stenosis (n=49) groups according to the results of digital subtraction angiography (DSA). The effects of the risk factors for cerebrovascular diseases and OSAHS on carotid stenosis in patients with ICDV were analyzed.Results There were significant differences in the proportions of alcohol consumption (χ2=8.56, P =0. 036), hypertension (χ2 = 13.20, P =0. 004) and carotid stenosis (χ2 =22.97, P =0. 006) between the no OSAHS and the mild, moderate and severe OSAHS groups. The univariate analysis showed that age (OR = 1. 066, 95% CI 1. 023- 1.112; P = 0. 003),hypertension (OR =3.587, 95% CI 1. 294- 9. 949; P =0. 014), alcohol consumption (OR =5.275,95% CI 1.855-15.001; P= 0.002) and OSAHS (OR= 1.073, 95% CI 1.033-1.115; P = 0. 000) were the risk factors for carotid stenosis. The multivariate logistic regression analysis showed that age (OR = 1. 113, 95% CI 1. 047-1. 182; P =0. 001), OSAHS (OR = 1. 096, 95% CI 1. 034-1. 160; P = 0. 000), and alcohol consumption (OR = 4. 292,95% CI 1. 217-15. 139; P = 0. 024) were the independent risk factors for carotid stenosis.Spearman rank correlation analysis suggested that the AHI levels were positively correlated with the degree of carotid stenosis (r = 0. 435, P = 0. 000). There were significant differences among the without stenosis (n =34), unilateral stenosis (n =22), and bilateral stenosis (n=27)groups (12.97 ± 10.04 vs. 21.40 ± 16.38 vs. 29.33 ± 13.81, F= 11.64, P<0.01).Conclusions OSAHS is an independent risk factor for carotid stenosis and it was positively correlated with the severity of carotid stenosis. AHI may reflect the degree of carotid stenosis and the range of neck vascular involvement to some extent.
4.Current state of secondary prevention medication for patients with high risk of recurrent ischemic stroke in Changzhou city
Donglin HAO ; Bona WU ; Lihui WANG ; Yuanfeng XU ; Jiajia WANG ; Zhiqing LIU ; Aijin MA
Chinese Journal of Geriatrics 2014;33(10):1060-1063
Objective To investigate the application of secondary prevention medication for patients with high risk of recurrent ischemic stroke in Changzhou city,analyze the reasons for decreased medication compliance,and evaluate the current secondary prevention medication.Methods We investigated 300 consecutive hospitalized patients with acute non-cardiogenic and ischemic stroke high risk.High risk of recurrent stroke was defined as ESSEN Stroke Risk Score (ESRS) ≥3.Different ESRS scales consisting of different parameters were analyzed.All of the patients received standard secondary prevention of ischemic stroke at discharge.After three months and a year follow up,antiplatelet therapy,therapy of risk factors (hypertension and diabetes mellitus),lipid lowering therapy,and medication compliance were investigated.Results Except for age (x2 =126.54,P =0.000) and previous cerebral ischemic stroke or transient ischemic attack (TIA) (x2 =21.27,P =0.000),there were no significant differences in other risk factors (hypertension,diabetes,previous myocardial infarction,heart diseases,smoke) in patients with different ESRS scale scores (all P> 0.05).Antiplatelet therapy utilization was 98.3% (295/300),antihypertensive and antidiabetic drug use rates were 95.0%(255/268) and 100%(72/72),statin use rate reached to 99% (297/300) at discharge.After three months follow up,medication compliance in hypertension and diabetes mellitus therapy was the best [88.1%(222/252)and 86.2% (56/65)],followed by aspirin [82.0% (228/278)],and clopidogrel [6.1% (17/278)].The medication compliance in lipid lowering therapy was the worst [60.1% (167/278)].After a year follow-up versus the previous three-month follow-up,the medication compliance in hypertension and diabetes mellitus therapy was increased,but had no significant difference [89.9 % (220/245) vs.88.1% (222/252),93.4%(57/61)vs.86.2%(56/65),P>0.05],and the medication compliances inantiplatelet therapy with aspirin and clopidogrel,and lipid lowering therapy were increased significantly [93.2% (245/263)vs.82.0% (228/278),30.8(81/263) vs.6.1% (17/278),88.9% (234/263) vs.60.1% (167/278),all P<0.01].The increment of use rate was higher in clopidogrel therapy than in aspirin therapy.Conclusions The secondary prevention medication achieves certain efficacies in patients with high risk of recurrent ischemic stroke in changzhou city.Long term follow-up and good communication between doctor and patient can effectively improve the medication compliance in secondary prevention,and can increase the use rate of antiplatelet therapy in patients with high risk of recurrent ischemic stroke.
5.Changes in homocysteine levels in patients with ischemic cerebral disease and obstructive sleep apnea-hypopnea syndrome
Bona WU ; Dengyue ZHAI ; Zhiming ZHOU ; Qin YIN ; Xinying FAN ; Ning WEI ; Wenhua LIU ; Gelin XU ; Xinfeng LIU
Chinese Journal of Neurology 2010;43(6):408-411
Objective To investigate the relationship between obstructive sleep apnea-hypopnea syndrome(OSAHS)and plasma homocysteine(Hcy)levels in patients with ischemie cerebrovascular disease(ICVD).Methods Seventy-six patients with ICVD were monitored with polysomnography(PSG) for 7-8 hours during sleeping.The levels of fibrinogen(FBG),high density lipoprotein cholesterol(HDLC),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG)and plasma Hey were assessed.Results Of the 76 ICVD patients,57 showed apnea symptom during sleeping,of which 53(69.7%)were diagnosed with OSAHS and 4 with central sleep apnea,According to the mean apnea-hypopnea index (AHI),the severity of apnea was classified as no apnea symptom(19 cases with mean AHI of 2.38±0.96 and Hey level of(8.78 ±2.01)μmol/L),mild apnea(21 cages with mean AHI of 14.14 ±4.37 and Hcy level of(12.91 ±3.00)μmol/L),moderate apnea(24 cases with mean AHI of 29.62±5.81 and Hcy level of(14.85 ±4.15)μmol/L)and severe apnea(8 cases with mean AHI of 46.75±2.82 and Hcy level of(19.30±4.82)μmol/L).The level of Hcy was statistical significant among these 4 groups(F=40.32,P<0.01)and correlated with the mean AHI(r=0.598,P<0.01).Conclusion Patients with ICVD have a high morbidity of OSAHS,mainly suffering from mild to moderate apnea;The plasma Hcy level elevates in the ICVD patients with OSAHS and is correlated with the severity of apnea.
6.Prognostic value of GCS and NIHSS in patients with acute top of basilar syndrome
Dengyue ZHAI ; Ning WEI ; Bona WU ; Tingting LU ; Wenhua LIU ; Haining GAO ; Zhaoyao CHEN ; Gelin XU ; Xinfeng LIU
Chinese Journal of Nervous and Mental Diseases 2010;36(3):141-144
Objective To assess the effectiveness of initial Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) as predictors for clinical outcomes in patients with top of the basilar syndrome (TOBS).Methods A total of 64 patients with TOBS were selected from Nanjing Stroke Registration Program (NSRP). Initial GCS and NIHSS were retrospectively evaluated by reviewing patients' records for details of clinical presentation and outcomes at 30 days measured by modified Rankin Scale (mRS) score. Patients were categorized as favorable outcome group (mRS 0-3) and unfavorable outcome group (mRS 4-6).Results The mean GCS was lower in the cases with mRS of 4-6 compared with those with mRS of 0-3 (P<0.01) and the mean NIHSS score was higher in favorable outcome group compared with unfavorable outcome group (P=0.011). In multivariate logistic regression analysis, after adjusting for age, gender and treatment approaches, the GCS OR was 0.301(95% CI 0.167~0.542), NIHSS OR was 1.436(95% CI 1.147~1.796), and both of them turned out to be the independent predictors of outcome at 30 days. ROC curve analysis suggested that GCS score of 10 represented a good cut-off point for predicting the outcome with the prognostic sensitivity of 87.9% and specificity of 83.9%. NIHSS score of 14 could also serve as a good cut-off point with the prognostic sensitivity of 63.6% and specificity of 77.4%.Conclusions Conclusions Both GCS and NIHSS can predict outcomes in patients with acute TOBS with GCS score ≤10 and NIHSS score ≥14 as the cutoff points of poor outcome. GCS cutoff point is more strongly predictive of outcome than that of NIHSS.