Predictive score of the outcomes after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Stroke has become the leading cause of disability and death in China. At present, intravenous thrombolysis is one of the most effective treatment for acute ischemic stroke, but not all patients can benefit from intravenous thrombolysis. In recent years, the exploration of predictive models for the outcomes after intravenous thrombolysis in patients with acute ischemic stroke has attracted increasing attention. This article systematically reviews the scoring models for predicting the functional outcome, death and symptomatic intracranial hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke, with the aim of screening the scoring system suitable for clinical application and providing reference for the clinical diagnosis, evaluation and treatment of acute ischemic stroke.

Correlation between post-stroke depression and cerebral microbleeds in elderly patients with ischemic stroke / 中华老年医学杂志

Objective To investigate the correlation between post-stroke depression(PSD) and cerebral microbleeds(CMBs)in elderly patients with ischemic stroke.Methods In the prospective study,220 elderly patients with ischemic stroke were enrolled and followed up to one month after onset.Finally a total of 214 elderly patients performed a follow-up.According to DSM-Ⅳ Diagnostic and Statistical Manual of Mental Disorders,patients were divided into the PSD group and non-PSD group.The degree of depression was evaluated by17-item Hamilton Depression Scale(HAMD-17)score,and patients were divided into mild depression,moderate depression and severe depression group.The loci number,distribution and location of CMBs lesions were assessed by SWI.Patients were divided into brain lobe type,deep lobe type and mixed type according to the CMBs lesion location.The influence of CMBs or not,loci number and location of CMBs lesions on PSD were compared.Results A total of 214 elderly patients with ischemic stroke were enrolled,in whom 84(84/214,39.3％)had PSD with 29(34.5％)males and 55(65.5％)females.According to the HAMD scale,there were 51 patients (60.7 ％) with mild depression,25 (29.8 ％) with moderate depression,and 8 (9.5 ％) with severe depression.The prevalence rate of CMBs was 62.5 ％ (32/51) in mild depression group,71.0 ％ (22/25) in moderate depression group,81.8 ％ (6/8)in severe depression group and 45.4 ％ (49/108)in non PSD group(all P=0.008).The number of CMBs lesions were(4.5±1.2)in mild depression group,(7.8± 2.0)in moderate depression group,(12.6±2.7)in severe depression group and(1.8±0.5)in non-PSD group,with the statistically significant differences between groups (F =2.79,P =0.041).The proportions of CMBs lesions location(brain lobe type,deep lobe type and mixed type)were 40.6 ％ (13/32),34.4％(11/32) and 25.0％ (8/32) in mild depression group,36.4％(8/22),40.9％(9/22) and 22.7％(5/22) in moderate depression group,33.3％ (2/6),50.0％ (3/6) and 16.7％ (1/6) in severe depression group,40.8％ (20/49),12.2％ (6/49) and 46.9％ (23/49) in non-PSD group,respectively (Fisher exact test,P =0.043).The proportions of CMBs lesions distribution(left side,right side and double side)were 37.5％(12/32),43.8％(14/32) and 18.8％(6/32) in mild depression group,36.4％ (8/22),40.9％ (9/22) and 22.7％ (5/22) in moderate depression group,50.0％ (3/6),33.3％ (2/6)and 16.7％(1/6) in severe depression group,36.7％(18/49),40.8％(20/49) and 22.5％(11/49) in non-PSD group,and the difference was not statistically significant (Fisher exact test,P =0.998).Conclusions The prevalence rate of CMBs,number of CMBs lesions and deep lobe type of CMBs are closely related to the degree of post-stroke depression in the elderly.The distribution of CMBs lesions has no relevance with the degree of post stroke depression in the elderly.Elderly patients with ischemic stroke at high risk of post-stroke depression can be identified by evaluating CMBs for early intervention,which is worthy of promotion in clinical work.

An investigation on prevalence and severity of cerebral microbleeds in patients with different stroke classifications of cerebral infarction / 中国基层医药

Objective To investigate the prevalence and severity of cerebral microbleeds (CMBs) in patients with different stroke classifications of cerebral infarction.Methods From October 2016 to December 2017,the clinical data of patients with acute cerebral infarction in the Second Affiliated Hospital of Xuzhou Medical University were collected through the prospective study.The SWI technique was used to screen the CMBs.According to the TOAST and OCSP classifications, the prevalence and severity of CMBs in patients with different stroke classifications of cerebral infarction were analyzed.Results A total of 254 patients with cerebral infarction were enrolled ,there were 136 patients(53.54%) in CMBs group and 118 patients(46.46%) in no CMBs group.The prevalence of CMBs in patients with different TOAST classifications was large artery atherosclerosis ( 54.29%), small -artery occlusion (64.15%), cardioembolism (40.43%), stroke of other determined etiology ( 33.33%), stroke of undetermined etiology(38.46%),and the difference was statistically significant (χ2 ＝12.206,P＝0.016).The prevalence of CMBs in patients with different OCSP classifications was total anterior circulation infarcts ( 43.75%), partial anterior circulation infarcts ( 51.19%), posterior circulation infarcts ( 49.18%), lacunar infarcts ( 67.53%), and the difference was statistically significant(χ2 ＝8.944,P＝0.030).The severity of CMBs in patients with different TOAST classifications was large artery atherosclerosis [mild(55.26%),moderate(26.32%),severe(15.79%)],small-artery occlusion[mild(25.00%),moderate (33.82%), severe (41.18%)], cardioembolism [ mild (57.89%), moderate (26.32%),severe(15.79%)),stroke of other determined etiology [ mild(50.00%),moderate (33.33%),severe (16.67%)],stroke of undetermined etiology [ mild(60.00%),moderate (20.00%),severe (20.00%)],and the difference was statistically significant (Fisher exact test,P＝0.025).The severity of CMBs in patients with different OCSP classifications was total anterior circulation infarcts [mild(57.14%),moderate(28.57%),severe(14.29%)], partial anterior circulation infarcts [ mild (52.50%), moderate (32.50%), severe (15.00%)], posterior circulation infarcts[mild( 50.00%), moderate (33.33%), severe (16.67%)], lacunar infarcts [ mild (25.00%), moderate (32.69%),severe (42.31%)], and the difference was statistically significant ( Fisher exact test, P ＝0.023 ). Conclusion The prevalence and severity of CMBs in patients with different stroke classifications of cerebral infarction are variable.The prevalence of CMBs in small -artery occlusion and lacunar infarcts are the highest and give first place to severe CMBs (number of lesions≥10).We should pay attention to these two stroke classifications by early recognition and taking targeted clinical strategies.

Investigation on pathogenesis and influencing factors of poor outcome in patients with wake-up stroke / 中华神经科杂志

Objective To explore pathogenesis and influencing factors of poor outcome in patients with wake-up stroke.Methods In this prospective study,patients with acute ischemic stroke who were hospitalized in the Department of Neurology of the Second Affiliated Hospital of Xuzhou Medical University from October 2016 to December 2017 were continuously collected.All patients were divided into wake-up stroke group and non-wake-up stroke group according to the onset time.The clinical data of demographics,vascular risk factors,imaging examination,laboratory examination of the two groups were collected to identify the pathogenesis of wake-up stroke.Followed up to six months of onset,the patients were divided into poor outcome (modified Rankin Scale (mRS) score ＞2) and good outcome (mRS score 0-2) subgroups according to mRS score.Multivariate Logistic regression analysis was used to determine the influencing factors of poor outcome in patients with wake-up stroke.Results A total of 178 patients with acute ischemic stroke were enrolled in the study,including 42 patients (23.60％) in the wake-up stroke group and 136 patients (76.40％) in the non-wake-up stroke group.Followed up to six months of onset,11 patients lost,and 167 patients were followed up finally.There were 40 patients (23.95％) in the wake-up stroke group,including 17 patients (42.50％) with poor outcome and 23 patients (57.50％) with good outcome.There were 127 patients (45.64％) in the non-wake-up stroke group,including 32 patients (25.20％) with poor outcome and 95 patients (74.80％) with good outcome.The difference of poor outcome between the two groups was statistically significant (x2=4.393,P=0.036).Comparison of the demographic and baseline data of the wake-up stroke group and the non-wake-up stroke group showed that the differences between variables such as atrial fibrillation and double-dose hypertension were statistically significant.Univariate analysis showed that there were statistically significant differences in vascular risk factors,Trial of Org 10172 in Acute Stroke Treatment etiology,stroke severity,number of stroke lesions,treatment patterns,and number of cerebral microbleeds between the poor and good outcome subgroups.Multivariate Logistic regression analysis showed that the moderate to severe stroke (odds ratio (OR)=3.838,95％ confidence interval (Co 2.162-5.890,P=0.018),the number of lesions in cerebral microbleeds (OR=2.113,95％CI 1.291-2.868,P=0.049) were independent risk factors for poor outcome of wake-up stroke.Intravenous thrombolysis (OR=0.427,95％CI 0.242-0.615,P=0.036) was an independent protective factor for poor outcome of wake-up stroke.Conclusions The onset of wake-up stroke is closely related to atrial fibrillation and reverse scoop hypertension with higher incidence of poor outcome.Early adequate imaging screening and stroke severity assessment have important reference to guide clinical treatment and predict outcome.

An investigation on prevalence and severity of cerebral microbleeds in patients with different stroke classifications of cerebral infarction / 中国基层医药

Objective@#To investigate the prevalence and severity of cerebral microbleeds(CMBs) in patients with different stroke classifications of cerebral infarction.@*Methods@#From October 2016 to December 2017, the clinical data of patients with acute cerebral infarction in the Second Affiliated Hospital of Xuzhou Medical University were collected through the prospective study.The SWI technique was used to screen the CMBs.According to the TOAST and OCSP classifications, the prevalence and severity of CMBs in patients with different stroke classifications of cerebral infarction were analyzed.@*Results@#A total of 254 patients with cerebral infarction were enrolled, there were 136 patients(53.54%) in CMBs group and 118 patients(46.46%) in no CMBs group.The prevalence of CMBs in patients with different TOAST classifications was large artery atherosclerosis(54.29%), small-artery occlusion(64.15%), cardioembolism(40.43%), stroke of other determined etiology(33.33%), stroke of undetermined etiology(38.46%), and the difference was statistically significant(χ2=12.206, P=0.016). The prevalence of CMBs in patients with different OCSP classifications was total anterior circulation infarcts(43.75%), partial anterior circulation infarcts(51.19%), posterior circulation infarcts(49.18%), lacunar infarcts(67.53%), and the difference was statistically significant(χ2=8.944, P=0.030). The severity of CMBs in patients with different TOAST classifications was large artery atherosclerosis[mild(55.26%), moderate(26.32%), severe(15.79%)], small-artery occlusion[mild(25.00%), moderate(33.82%), severe(41.18%)], cardioembolism[mild(57.89%), moderate(26.32%), severe(15.79%)), stroke of other determined etiology[mild(50.00%), moderate(33.33%), severe(16.67%)], stroke of undetermined etiology[mild(60.00%), moderate(20.00%), severe(20.00%)], and the difference was statistically significant(Fisher exact test, P=0.025). The severity of CMBs in patients with different OCSP classifications was total anterior circulation infarcts[mild(57.14%), moderate(28.57%), severe(14.29%)], partial anterior circulation infarcts[mild(52.50%), moderate(32.50%), severe(15.00%)], posterior circulation infarcts[mild(50.00%), moderate(33.33%), severe(16.67%)], lacunar infarcts[mild(25.00%), moderate(32.69%), severe(42.31%)], and the difference was statistically significant(Fisher exact test, P=0.023).@*Conclusion@#The prevalence and severity of CMBs in patients with different stroke classifications of cerebral infarction are variable.The prevalence of CMBs in small-artery occlusion and lacunar infarcts are the highest and give first place to severe CMBs(number of lesions≥10). We should pay attention to these two stroke classifications by early recognition and taking targeted clinical strategies.

Screening and risk factors for depression in elderly stroke patients within one month after onset / 中华健康管理学杂志

Objective To investigate the screening of elderly patients with post?stroke depression (PSD) and to analyze risk factors. Methods In this prospective study, 220 elderly patients with ischemic stroke were enrolled. At one month after onset, 214 aged patients completed follow?up. According to the DSM?IV diagnosis standard, the patients were divided into PSD and non?PSD groups. Seventeen items of the Hamilton Depression Scale (HAMD) was used to evaluate the degree of depression, and the patients were divided into mild, moderate, and severe depression groups. The demographic and baseline clinical characteristics were compared. Multivariate logistic regression analysis was used to identify the risk factors of PSD in individuals. Results (1) Of the 214 aged patients with ischemic stroke who completed follow?up, 84 had PSD including 29 (34.52%) men and 55 (65.48%) women. The detection rate of PSD was 39.25%. According to the HAMD, 51 (60.72%) aged patients were diagnosed with mild depression, 25 (29.76%) with moderate depression, and 8 (9.52%) with serious depression. (2) Multivariate logistic regression analysis showed that advanced age (>75 years old), female sex, joblessness, being divorced or widowed, having cerebral microbleeds, experiencing social and family environment tension, having low cultural exposure, having moderate and severe neurologic deficits, and having a left?side lesion were the independent risk factors of PSD in elderly patients. Conclusion PSD is common in elderly patients. Evaluation of these risk factors can help identify aged patients at high risk for PSD to allow early intervention, which is worth promoting in clinical work.

An investigation on nutritional risk screening and risk factors of malnutrition in younger patients with stroke / 中华健康管理学杂志

Objective To evaluate the nutritional risk screening for younger patients with stroke and to explore risk factors of malnutrition. Methods Younger patients with stroke were enrolled in a prospective way. The patients were evaluated by nutritional risk screening 2002 (NRS 2002) at their admission for nutritional risk screening, and were divided into nutritional risk group and no nutritional risk group according to the evaluation results. Prealbumin less than 200 mg/L was defined as malnutrition. Demographic and baseline clinical characteristics of the patients were analyzed with multivariate logistic regression analysis to determine independent risk factors for malnutrition at the admission and the 14th day. Results (1) A total of 152 young stroke patients were enrolled, including 51 in nutritional risk group, 101 in no nutritional risk group, the rate of nutritional risk was 33.6%(51/152). (2) The rate of malnutrition at admission was 13.8%(21/152), the rate of malnutrition in nutritional risk group was 25.5%(13/51), and 7.9%(8/101)in no nutritional risk group on admission. While the rate of malnutrition was 32.2%(49/152), including the rate of malnutrition in nutritional risk group was 60.78%(31/51)and 17.8%(18/101)in no nutritional risk group was at the 14th day of admission. (3) Multivariate Logistic regression analysis showed that advanced age (from 36 to 45 years), sex, diabetes, hyperthyroidism were independent risk factors for malnutrition in younger patients with stroke. Recent history of surgery and smoking, stroke-associated pneumonia, post-stroke depression, swallowing disorder, sleep disorder, moderate and severe neurologic deficits were also risk factors for malnutrition. Conclusion The incidence of malnutrition in youngerpatients with stroke were higher, and earlier nutritional risk screening and nutritional support in these patients were urgent.

Application of team-based learning and lecture-based learning combined with PDCA circle teaching in clinical teaching of neurology / 中华医学教育探索杂志

Objective To explore the teaching feasibility and practicability on team-based learning (TBL) and lecture-based learning (LBL) combined with PDCA circle teaching in clinical teaching of neurol-ogy, and evaluate its teaching effect. Method 100 cases clinical medical professional training students were chosen, divided into experiment group and control group, with 50 cases in each group. Control group used TBL and LBL teaching while experiment group used combined with PDCA circle teaching on the basis of control group. After the teaching, the teaching effects difference between two groups was evaluated and compared. Result The theoretical examination scores in experiment group (85.95 ±7.63) was higher than that in control group (77.31±5.38), and the difference was statistically significant (t=2.126, P=0.034). The practical operation scores in experiment group (82.37±5.15) was higher than that in control group (76.62± 4.35), and the difference was statistically significant (t=2.173, P=0.029). In anonymous satisfaction survey, the average coutent degree with teaching in experiment group is higher than control ( 92% vs . 82%) . Conclusion TBL and LBL combined with PDCA circle teaching improves the students' basic theory, prac-tical operation and doctor-patient communication ability, whose satisfaction has also significantly increased, which is worth popularizing in the clinical practice teaching of neurology.

Comparison of the clinical effect of different doses of rosuvastatin in the treatment of hyperlipidemia and carotid atherosclerotic plaque in young ischemic stroke patients / 中国基层医药

Objective To observe the efficacy and safety of rosuvastatin in the treatment of hyperlipidemia and carotid atherosclerotic plaque in young ischemic stroke patients.Methods In prospective study,264 young ischemic stroke patients with hyperlipidemia and carotid atherosclerotic plaque were randomly divided into low dose group,middle dose group,high dose group,88 cases in each group.All patients were given rosuvastatin immediately after dinner,in doses of 5mg,10mg,20mg,respectively,for eight months.Then,the changes of hyperlipidemia and carotid atherosclerotic plaque in the three groups were surveyed,and its safety by the observation of clinical symptoms and monitoring of adverse reactions after eight months were assessed.Results Before treatment,the blood fat and carotid atherosclerosis plaque index in the three groups had no statistically significant differences (all P >0.05). After treatment,the total cholesterol,triglycerides,low -density lipoprotein cholesterol of the high dose group were (1.67 ±0.68)mmol/L,(3.23 ±0.53)mmol/L,(1.83 ±0.62)mmol/L,which of the middle dose group were (1.93 ±0.74)mmol/L,(3.73 ±0.23)mmol/L,(2.24 ±0.73)mmol/L,which of the low dose group were (2.16 ± 0.77)mmol/L,(4.06 ±0.93)mmol/L,(2.93 ±0.35)mmol/L.These indicators were decreased than before treat-ment [(2.79 ±0.72)mmol/L,(5.40 ±0.67)mmol/L,(3.64 ±1.03)mmol/L,(2.75 ±0.81)mmol/L,(5.59 ± 0.95)mmol/L,(3.43 ±0.92)mmol/L and (2.83 ±0.53)mmol/L,(5.84 ±0.79)mmol/L,(3.83 ±0.88)mmol/L].The decrease of the high dose group was higher than the middle and low dose group,the difference was statistically significant(F =6.61,P 0.05),and no serious adverse reaction was found.Conclusion The high dose rosuvastatin treatment can reverse the nature of plaque, decrease the thickness of the plaques and lower blood lipid of young ischemic stroke with hyperlipidemia and carotid atherosclerotic plaque,which is better than middle and low dose,and has better security.There is no serious adverse reaction.It is worth for clinical promotion.

Effects of FKBP51 acting on Caspase-3 and rat hippocampal CA1 area neuronal necrosis in cerebral ischemia reperfusion injury / 中国基层医药

Objective To explore the effect of FKBP51 acting on Caspase-3 and hippocampal CA1 area neu-ronal necrosis in cerebral ischemia reperfusion injury of rat.Methods SD rats were randomly divided into Sham group,ischemia reperfusion group ( I/R group ) , TE buffer group ( TE group ) , FKBP51 antisense oligonucleotide group (FKBP51 ASODN group) and FKBP51 missense oligonucleotide group (FKBP51 MSODN group).Transient global cerebral ischemia rats models were made by four-vessel method.We used Western blot to detect the expression of FKBP51,the effect of FKBP51 ASODN to FKBP51 expression and Caspase-3 activity;while we used HE staining technique to detect FKBP51 ASODN effect to rat hippocampal CA1 area neuronal necrosis.Results (1) In Sham group and I/R group (0min,15min,30min,1h,3h,6h,1d,3d),FKBP51 expressed,and the difference among the groups was no statistical significance (F=0.64,P>0.05).(2)The expression of FKBP51 in FKBP51 ASODN group was obviously reduced, and the difference was statistically significant compared with Sham group ( t =8.21, P <0.05).(3)The expression of Cleaved-Caspase-3 in Sham group obviously declined than the other groups,the differ-ence between them was statistically significant (F=12.31,P<0.05);The expression of FKBP51 in FKBP51 ASODN group was decreasing compared with FKBP51 MSODN group,and the difference was statistical significance(t=9.71, P<0.05).(4)HE staining showed:the number of Sham group (186.3 ±2.5) hippocampal CA1 pyramidal cells was most.The cells arranged densely,and nucleoli were large and round,the difference was statistically significant com-pared with the other groups (χ2 =81.91,P<0.05);The hippocampal CA1 pyramidal cells of I/R group (15.4 ± 2.6),TE group (18.5 ±2.2) and FKBP51 MSODN group (17.5 ±1.8) were almost completely disappeared,only left a few residual cells,a great quantity of denaturated cells which presented karyopykosis,tinctorialed endochylema, ruptured of membrane and released cell content;the hippocampal CA1 pyramidal cells FKBP51 ASODN group (92.8 ±2.6) survival increased significantly compared with other group,the difference was statistically significant (χ2 =52.36,P<0.05).Conclusion In cerebral ischemia reperfusion injury,FKBP51 can enhance the activation of Caspase-3 (Cleaved-Caspase-3) expression and inhibit the survival of the neurons.

Effect of FKBP51 on JNK pathway in cerebral ischemia-reperfusion injury / 中国医师杂志

Objective To investigate effect of FK506 binding protein 51 (FKBP51) on the c-JunN-terminal kinase (JNK) pathway in cerebral ischemia-reperfusion injury.Methods Transient global cerebral ischemia rat models were made by four-vessel method.Healthy male SD (Sprague Dawley) rats were randomly divided into:sham group,ischemia/reperfusion group (I/R group),FKBP51 antisense oligonucleotide group (FKBP51 ASODN group),FKBP51 missense oligonucleotide group (FKBP51 MSODN group),and solvent control group (TE group).The effect of FKBP51 ASODN on expression of FKBP51 protein and JNK was detected,and c-Jun phosphorylation was detected by Western blot.Results (1) FKBP51 protein expression in the FKBP51 ASODN group was reduced.The change of FKBP51 protein expression between the FKBP51 ASODN and sham groups was statistically significant (P ＜ 0.05).(2) The expression differences of total JNK protein between all the groups were not statistically significant (P ＞ 0.05).The expression of p-JNK in sham group was significantly less than the other groups (P ＜ 0.05).The expressions of p-JNK in I/R 3d,TE,and FKBP51 MSODN groups were higher relative to Sham group; however,the differences among those three groups were not statistically significant (P ＞ 0.05).The expression of p-JNK in FKBP51 ASODN group was significantly less than FKBP51 MSODN group (P ＜ 0.05).(3) The expression differences of total c-Jun protein among all groups were not statistically significant (P ＞ 0.05).The expression of p-c-Jun in sham group was significantly less than the other groups (P ＜ O.05).The expressions of p-c-Jun in I/R 6 h,TE,and FKBP51 MSODN groups were higher relative to the sham group; however,the differences among those three groups were not statistically significant (P ＞ 0.05).The expressions of p-c-Jun in FKBP51 ASODN group was significantly less than FKBP51 MSODN group (P ＜ 0.05).Conclusions FKBP51 might activate JNK signaling pathway in cerebral ischemia-reperfusion injury.

Effect of the FKBP51 · PHLPP · Akt signal module on the phosphorylation of Akt and hippocampal neuronal injury after the cerebral ischemia/reperfusion / 中华行为医学与脑科学杂志

Objective To investigate the effects of the FKBP51 · PHLPP · AKT signal module on the phosphorylation of Akt and hippocampal neuronal injury after the cerebral ischemia / reperfusion induced neuronal death in rat hippocampus.Methods Transient(15 min)brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats.6 rats were used in each group.The antisense oligodeoxynucletides(AS ODN)of PHLPP2 (PH domain and leucine rich repeat protein phosphatases) was used to suppress the assembly of FKBP51 · PHLPP · Akt signal module by intracerebroventricular infusion once per day for 3 days before ischemia.After 6 hours reperfusion,interactions of PHLPP2 and FKBP51 (FK506 binding protein 5) with Akt were detected by immunoprecipitation (IP) and the phosphorylation of Akt was detected by western blot (IB).After 5 days reperfusion,rats were perfusion-fixed with paraformaldehyde and Hematoxylin-Eosin staining was used to examine the survival number of CA1 pyramidal cells of hippocampus.Results Compared to PHLPP2 MS ODN group(1.24±0.24,1.68±0.11,0.58±0.01),PHLPP2 AS ODN suppressed the assembly of the FKBP51 · PHLPP · Akt signaling module(1.06±0.01,1.04±0.13),and increased the phosphorylation of Akt(0.76±0.02) (P＜0.05).Furthermore,compared to PHLPP2 MS ODN group (20.1±2.5),the number of surviving neurons significantly increased in PHLPP2 AS ODN group(88.3±2.7)(P＜0.05).Conclusion The increasing assembly of FKBP51 · PHLPP · Akt signal module can damage CA1 pyramidal cells of hippocampus by inhibiting the phosphorylation level of Akt.

Effects of a Rho kinase inhibitor fasudil hydrochloride on GluR6 and neuronal apoptosis in cerebral ischemia/reperfusion injury / 中华行为医学与脑科学杂志

Objective To investigate the neuralprotective effect of Rho kinase inhibitor fasudil hydrochloride in cerebral ischemia/reperfusion injury in rats.Methods The SD rats were randomly divided into four groups:the sham group,the ischemia/reperfusion group,the fasudil hydrochloride group and the physiological saline group.Fasudil hydrochloride were injected intraperitoneally 30 minutes before ischemia.And the physiological saline group were treated with the intraperitoneal injection of the same volume of saline.The phosphorylation and protein expression of GluR6 at 6 hours during reperfusion were detected using immunoprecipitation and immunoblotting analysis to examine the effect of Fasudil hydrochloride.Furthermore,TUNEL staining was used to examine the apoptosis of neurons in rat hippocampal CA1 regions after 3 days reperfusion.Results 1.Immunoprecipitation and immunoblotting analysis were used to analyze the phosphorylation of GluR6 in serine site.The results showed that the GluR6 serine phosphorylation level increased significantly at 6h of reperfusion compared with the sham group (P＜0.05).Fasudil hydrochloride group could inhibit the increased phosphorylation of GluR6 at 6h of reperfusion compared with the ischemia/reperfusion group and saline group,respectively (P ＜ 0.05).2.TUNEL staining was used to examine the apoptosis of neurons in 3 days after reperfusion in CA1 regions of hippocampus.The results indicated that significant numbers of TUNEL positive cells (40.20 ± 2.77) were observed 3 days after ischemia/reperfusion.The numbers of viable neurons per 1 mm length of CA1 pyramidal cells were quantitatively analyzed.Fasudil hydrochloride markedly decreased the neuronal loss compared with the ischemia/reperfusion group (19.80 ± 2.86) (P＜0.05).Conclusion Fasudil hydrochloride can inhibit induced phosphorylation of GluR6 by the ischemia/reperfusion.Fasudil hydrochloride can reduce the neurons apoptosis in hippocampal CA1 regions,and perform a neuralprotective effect on ischemia/reperfusion injury in rats.

Rho kinase inhibitor fasudil protect neurons in hippocampal CA1 region following cerebral ischemia reperfusion through inhibiting MLK3-JNK signal transduction pathway in rats / 国际脑血管病杂志

Objective To investigate the effect of Rho kinase inhibitor fasudil on taxed lineage kinase 3 (MLK3), c-Jun NH2-terminal kinase (JNK) phosphorylation, caspase-3expression, and neuronal injury in hippocampal CA1 region follwong cerebral ischemic rep erfusion in rats. Methods A total of 72 Sprague-Dawley rats were randomly divided into sham operation, ischemia-reperfusion, normal saline, and fasudil groups. A global cerebral ischemic model was prepared by four-vessel ligation. The levels of MLK3 and JNK phosphorylation, and caspase-3 expression were detected by Western blot analysis. Cresy1 violet staining was used to detect the numbers of survival neurons in hippocampal CA1 region. Results When 6 hours after ischemia-reperfusion, the level of MLK3 phosphorylation in the fasudil group (1.13 ± 0. 03)was significantly lower than that in the normal saline group (2. 08 ± 0. 01 ,P = 0. 000 3), while the levels of MLK3 was no significant difference. When 3 hours after ischemia-reperfusion, the level of JNK phosphorylation in the fasudil group (1.27 ±0. 02)was significantly lower than that in the normal saline group (2.09 ±0. 01, P=0. 000 2), while the levels of JNK was no significant difference. When 6 hours after ischemia-reperfusion, the expression level of caspase-3in the fasudil group (1.28 ± 0. 02) was significantly lower than that in the normal saline group (2. 10 ± 0. 01, P = 0. 000 6). When 5 days after ischemia-reperfusion, the pyramidal cells in hippocampal CA1 region almost completely disappeared in the ischemia-reperfusion group, and only a few cells left (9. 8 ±2. 1). The numbers of survival pyramidal cell (8. 28 ± 3.2) in hippocampal CA1 region in the fasudil group was significantly more than that in the normal saline group (11.8 ± 1.6, P ＜0. 05). Conclusions Fasudil may significantly inhibit the ischemia-reperfusion-induced phosphorylation of MLK3 and JNK, as well as the expression of caspase-3, and thus reduce neuronal injury in hippocampal CA1 region.