Curative effect of edaravone in the treatment of patients with transient cerebral ischemia and its mechanism / 中国基层医药

Objective To study the curative effect of edaravone in the treatment of patients with transient cerebral ischemia and its mechanism.Methods 92 patients with TIA treated in our hospital from January 2015 to December 2015 were selected,they were randomly divided into observation group and control group,with 46 cases in each group.Both two groups were given conventional treatment,while the observation group added intravenous infusion of edaravone injection,two groups were treated for 2 weeks.Then,the efficacy and adverse reactions during treatment in two groups were compared.The levels of serum tumor necrosis factor alpha(TNF -α),transforming growth factor beta 1(TGF -β1)and matrix metalloproteinase -9(MMP -9)were detected by enzyme -linked immunosorbent assay(ELISA)in two groups before treatment and 1d,4d,7d,14d after treatment.The levels of high/low shear viscos-ity(HSV /LSV),plasma viscosity(PV),as well as fibrinogen(Fib)were also compared before treatment and 14d after treatment.Results The total effective rate of the observation group was 89.13%,which was significantly higher than 71.74% in the control group(χ2 =4.420,P <0.05).The levels of HSV,LSV,PV and Fib in two groups 14d after treatment were significantly lower than before treatment,which of the observation group were significantly lower than the control group,the differences were statistically significant(P <0.05).The serum levels of TNF -α[(5.99 ± 2.36)pg/mL,(5.82 ±2.34)pg/mL],TGF -β1 [(13.94 ±3.18)pg/L,(12.33 ±3.57)pg/L]and MMP -9 [(42.94 ±11.65)ng/mL,(38.26 ±17.58)ng/mL]in the observation group at 7d and 14d after treatment were sig-nificantly lower than before treatment,the differences were statistically significant (t =4.703,6.031,5.667;5.074, 7.623,6.150;all P <0.05),and which in the observation group were lower than the control group in the same peri-od,the differences were statistically significant(t =2.025,5.344,5.894;2.616,6.120,2.228;all P <0.05).The levels of above indicators 14d after treatment in the control group were significantly lower than before treatment,the differences were statistically significant(P <0.05).There were no serious adverse reactions in the two groups during the treatment.Conclusion Edaravone has obvious curative effect in the treatment of patients with TIA,which works by regulating the hemodynamic and the levels of TNF -α,TGF -β1 and MMP -9,it is safe and worthy of promotion.

Clinical Observation of Clopidogrel Combined with Aspirin in the Treatment of Transient Ischemic Attack in the Elderly / 中国药房

OBJECTIVE:To observe the efficacy and safety of clopidogrel combined with aspirin in the treatment of transient ischemic attack in the elderly. METHODS:90 elderly patients with transient ischemic were randomly divided into observation group(50 cases)and control group(40 cases). All patients received conventional treatment,statins,low molecular weight dextran and urokinase,etc.,symptomatic treatment was conducted for patients combined with other underlying diseases. Based on it,con-trol group received 100 mg Aspirin enteric-coated tablet,once a day;observation group additionally received 75 mg Clopidogrel bi-sulfate tablet,once a day. No other antiplatelet drugs were allowed. They treatment for 6 months. Clinical efficacy,platelet func-tion indexes(CD63,CD62p)before and after treatment,recurrence rate and incidence of cerebral stroke after 6 months follow-up in 2 groups were observed,and the incidence of adverse reactions was recorded. RESULTS:The total effective rate in observation group was significantly higher than control group,recurrence rate and incidence of cerebral stroke were significantly lower than con-trol group,the differences were statistically significant(P<0.05). After treatment,CD63 and CD62p levels in 2 groups were sig-nificantly lower than before,and observation group was lower than control group,the differences were statistically significant(P<0.05). And there were no obvious adverse reactions during treatment. CONCLUSIONS:Based on conventional treatment,clopido-grel combined with aspirin shows better efficacy than aspirin alone in the treatment of transient ischemic attack in the elderly,it can reduce the incidence of cerebral stroke and recurrence rate,with good safety.

Remifentanil alleviates transient cerebral ischemia-induced memory impairment through suppression of apoptotic neuronal cell death in gerbils / 대한마취과학회지

BACKGROUND: During neurosurgical procedures, patients are often exposed to hypoxic and ischemic brain damage. Cerebral ischemia leads to neuronal cell death and eventually causes neurological impairments. Remifentanil is a new ultra-short acting phenylpiperidine opioid analgesic. In this study, we evaluated remifentanil to determine if it exerts an anti-apoptotic effect in the hippocampal dentate gyrus following transient global ischemia in gerbils. METHODS: Step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemical staining for caspase-3 were performed. RESULTS: The numbers of TUNEL-positive cells and caspase-3-positive cells in the dentate gyrus were increased by ransient global ischemia. Latency in the step-down avoidance task was increased by transient global ischemia. Results revealed that apoptotic cell death in the dentate gyrus was increased significantly following transient global ischemia, resulting in memory impairment. However, treatment with remifentanil suppressed ischemia-induced apoptosis in the dentate gyrus, thereby alleviating the memory impairment that was induced by ischemic cerebral injury. CONCLUSIONS: These results indicate that remifentanil may exert a neuroprotective effect on ischemic brain damage during surgery.

Neuroprotection of Alpinia katsumadai Seed Extract against Neuronal Damage in the Ischemic Gerbil Hippocampus is Linked to Altered Brain-Derived Neurotrophic Factor / 한국실험동물학회지

The extract of Alpinia katsumadai, a member of the family Zingiberaceae, shows anti-inflammatory effects and antioxidant activity. We observed the neuroprotective effects of the extract from Alpinia katsumadai seed (EAKS) against ischemic damage in gerbils administered oral EAKS (25, and 50 mg/kg) once a day for 7 days before transient cerebral ischemia. In the 50 mg/kg EAKS-treated ischemia group, about 67% of neurons in the hippocampal CA1 region (CA1) survived after ischemia/reperfusion (I/R) based on cresyl violet staining. We observed that EAKS treatment significantly maintained brain-derived neurotrophic factor (BDNF) immunoreactivity in the ischemic CA1 region after I/R. In addition, protein levels of BDNF in the 50 mg/kg EAKS-treated ischemia group were much higher than those in the vehicle-treated ischemia group after I/R. These findings indicate that repeated supplementation of EAKS protects neurons from ischemic damage, such that BDNF is distinctively maintained in ischemic areas.

Alterations of chaperone hsp40 anti its influence on the CAI neurons death after transient cerebral ischemia / 中华急诊医学杂志

Objective To investigate the alteration of chaperone hsp40 and its effects on the dealyed neuron death in the CAI neurons after transient cerebral ischemia.Method Twenty-minute transient global ischemia rat model was used.Following different repeffusion period,all the 28 wistar rats were divided into sham-operation group ,4-hour recovery group,24-honr recovery group and 72-hour recovery gronp,7 ratsin in each group,Immunochemistry and laser scanning confocal microscopy were used to observe the distributional alteration of hsp40 in the neurons.Differential centrifuge and westemblot analysis were used to analyze the quantitative alteration of hsp40 and its redistribution in the neurons.Results lnanunechemistry and laser scanning confocal microscopy showedthe reduction of hsp40 first in cytosol,then in the nucleus until all the neurons in the CAI region died.Differential centrifuge and westemblot analysis showed the quantity of hsp40 decreased from (1.00_+0.21) to (0.23±0.13)(P<0.01) after 24-hour repeffusion;the quantity of hsp40 in the protein aggregates increased from (1.00±0.18) to(8.61±1.89)(P<0.01) after24-hour reperfusion.Conclusions The reduction of hsp40 in the neurons of hippocampus CA1 region is an important factor resulting in protein aggregates formation.

The Change of Expression in Amyloid Precursor Protein mRNA and Amyloid Precursor Protein by Transient Ischemia

Although the mechanism has not been clearly understood, it has been reported that various altered gene expressions are induced by cerebral ischemia. In order to investigate the effects of transient cerebral ischemia on the amyloid precursor protein(APP) metabolism, the 3 isoforms of APP mRNA and the APP were examined. Rats were given ischemic insult through middle cerebral artery occlusion and reperfusions using blunted 4-0 nylon thread after exposure of cervical region. Groups were assigned with each being 1 hour occlusion and 1hr, 3hrs, 8hrs, 1day, 3days, 7days after reperfusion. The rats were then sacrificed and cerebral cortex of each animal was dissected. The mRNA level of APP770, 751, 695 was investigated by reverse transcription coupled polymerase chain reaction (RT-PCR) and the protein amount of APP was investigated by Western blotting method. The results showed that transient ischemia induced the change of APP mRNA. The APP mRNA which encodes the KPI(Kunitz-type protease inhibitor) domain began to increase after 1 day, reaching a maximun at 3 days, and then decreased to control level in the 7 days. The protein level of APP was same until 7 days. We conclude that transient cerebral ischemia alters the gene expression of APP isoforms. Therefore, we speculate that some factors regulating the splicing of APP gene transcript may also undergo ischemia-induced changes and the increase in levels of KPI-APP following ischemia might be associated with pathological changes during the ischemic process.

Clinical Efficacy of Danshen and Chuanxiongqin Injection for Frequent Attacks of Transient Cerebral Ischemia: Observation of 40 Cases / 中国药房

OBJECTIVE:To observe the clinical curative effect of Danshen and Chuanxiongqin injetion for frequent attacks of transient cerebral ischemia. METHODS: A total of 78 patients with frequent attacks of transient cerebral ischemia were enrolled:40(treatment group) were assigned to receive Danshen and Chuanxiongqin injection 10 mL with 0.9% physionlogical saline 200 mL iv gtt q.d, 38 (control group) to receive Xuesaitong injection 10 mL with 0.9% physiological saline 200 mL iv gtt q.d for 14 days(for both group).RESULTS: There were significant differences between the treatment group and the control group in effective rate (95.00% vs.57.89% respectively) (P

Studies on the mechanism responsible for delayed neuronal death in hippocampus after transient cerebral ischemia in gerbils / 中国病理生理杂志

DND in the gerbil hippocampus was performed by bilateral occlusion of carotid arteries for 20 min followed by reperfusion 2 or 7 days. The contents of Ca~(2+) and MDA in drosal hippocampus were measured after two days reperfusion. Neuronal density in CA1 sector of hippocampus was used as an parameter. Effects of nimodipine and Superoxide dismutase (SOD) on DND in hippocampus were observed after 7 days reperfusion.The results indicated that the levels of Ca~(2+) and MDA were increased significantly. DND in hippocampal CA1 sector was ameliorated by both nimodipine and SOD significantly. It was suggested that Ca~(2+) and Iipid peroxidation play an important role in the development of DND hippocampus after transient forebrain ischemia in gerbils. Calcium Antagonist and free radical scavenger have obvious protective effects on DND in hippocampus.

A Morphological Study on Hippocampal Damage after Transient Cerebral Ischemia in Gerbils / 昆明医科大学学报

Gerbils were sacrificed at 12 hours,1,2,4 and 7 days after a 20 minute occlusion of both carotid arteries.The morphological changes of the dorsal hippocampus were observed at varying times of recirculation.Under a light microscope,the histopathologis changes of the hippocampus were observed in several subfields.The neurons in CA_1 sector were particularly sensitive to ischemia.The changes in the CAl subfield were very slow,and almost all of the pyramidal cells in the CAl sector were destroyed and disappeared after a 4 day recirculation. The CAl subfield was selected for electron microscopy,and an increase in the cisterns of the endoplasmic reticulum was observed after the 1-2 day recirculation.The results suggest that the hippocampal damage in CAl sector after transient cerbral ischemia is different from the neuronal damage of the other parts of the brain.Delayed neuronal death and selective vulnerability were the main characteristics.