雌激素在诸多急慢性神经系统疾病中发挥神经保护作用,其具体机制目前认为主要包括神经营养作用、抗凋亡作用和抗炎作用[1].在癫痫中研究最多的是雌激素神经营养作用[2-3],对其抗炎作用研究甚少,而免疫炎症机制在癫痫中的作用越来越受重视[4-5].化学致痫剂、电刺激等多种癫痫模型中均可观察到痫性发作后快速诱导的炎症反应,主要包括小胶质细胞和星形胶质细胞活化、经典炎性细胞因子如白细胞介素( interleukin,IL-1β)、肿瘤坏死因子(tumor necrosis factor,TNF-α)表达增加,同时伴随下游炎症级联反应产生[6].炎症反应在一定程度上可促进癫痫发作病理生理进程,并可导致癫痫相关的海马病理性改变[4,6-7]。
目的 探讨过氧化物酶体增殖物激活受体γ辅激活子(peroxisome proliferator-activated receptor-γ coactivator,PGC)-1α在海人酸(kainic acid,KA)诱导的培养大鼠海马神经元氧化应激及神经损伤中的作用.方法 离体培养大鼠海马神经元,采用电穿孔基因转染技术分别转染PGC-1α shRNA质粒和空载体质粒.培养7天后,用KA刺激上述海马神经元24 h,检测转染空载体质粒海马神经元(空白对照组,n=10)、KA刺激的转染PGC-1α shRNA质粒(实验组,n=11)和KA刺激的空载体质粒海马神经元(KA对照组,n=10)的谷胱甘肽(glutathione,GSH)含量、超氧化物歧化酶(superoxidase dismutase,SOD)和乳酸脱氢酶(lactic dehydrogenase,LDH)活性变化.FJB染色检测KA刺激24 h后实验组和KA对照组培养大鼠海马神经元神经损伤情况.结果 KA刺激24 h,培养的大鼠海马神经元GSH含量和SOD活性分别为(5.74±0.54) μmol·L-1·μg-1 protein和(10.57±1.25) U/mg protein,较空白对照组显著降低[(9.38±0.72) μmol·L-1·μg-1 protein,P<0.01;(23.12±3.23) U/mg protein,P<0.01];LDH活性为(2.21±0.18) mmol NADH,H+/min/100 mg protein,较空白对照组海马神经元显著增高[(1.29±0.09) mmol NADH,H+/min/100 mg protein,P<0.01].转染PGC-1αshRNA质粒组,KA刺激24 h海马神经元GSH含量和SOD活性分别为(3.37±0.42)μmol·L-1·μg-1 protein和(4.54±0.91) U/mg protein,较KA对照组海马神经元明显降低(P均<0.05);LDH活性为(2.74±0.19) mol/NADH+/min/mg protein,较KA对照组海马神经元显著增加(P<0.01).FJB染色显示转染PGC-1α shRNA质粒组,KA刺激24h培养大鼠海马神经元损伤较KA对照组明显增加(P<0.05).结论 PGC-1α基因下调加重KA刺激后培养大鼠海马神经元损伤,可能与其加重氧化应激损伤有关.
BACKGROUND Curcumin, an active ingredient of turmeric with antioxidant and anti-inflammatory properties has recently been reported to have anticonvulsant effects in several animal models of epilepsy. This study aimed to investigate the effects of curcumin on the pilocarpine rat model of status epilepticus. METHODS The effect of intraperitoneal administration of curcumin (30, 100, and 300 mg/kg) on pilocarpine-induced seizures in rats was tested. The correlation between seizure activity and hippocampal levels of nitric oxide synthase and free radicals was quantified. Whether curcumin treatment modulated these parameters was also investigated. RESULTS Curcumin significantly increased seizure threshold at doses of 100 and 300 mg/kg. Rats with pilocarpine- induced seizures showed significantly elevated levels of malonaldehyde, nitric oxide synthase, and lactate dehydrogenase, but decreased levels of superoxide dismutase and glutathione compared with normal control rats. At doses of 100 and 300 mg/kg, curcumin reversed the effects of pilocarpine-induced seizures on nitric oxide synthase, lactate dehydrogenase, glutathione, and superoxide dismutase. However, curcumin did not restore the elevated malonaldehyde levels. CONCLUSION Curcumin has anticonvulsant activity in the pilocarpine rat model of seizures, and that modulation of free radicals and nitric oxide synthase may be involved in this effect.
In view of feature that temperature of motor could increase in abnormal condition,the paper proposed a design scheme of temperature monitoring system of motor based on 1-wire bus.Taking motor of fuming furnace of some company as an example,it introduced hardware structure and design of upper computer software of the system in details and gave problems needed pay attention to in process of installation and debugging of the system.The actual application showed that the system has high measuring precision and meets engineering requirements.
A new temperature control method based on grey PID algorithm was put forward.In liquor fermentation process,gray model has been established based on gray system theory which could estimate and compensate the uncertain part of the system.The experimental results showed that such method could effectively improve system response speed and system control accuracy.
临床资料患者男性,55岁,因"双耳耳鸣、听力下降1个月,头痛9 d,口角歪斜2 d"于2009年1月20日入院.患者于2008年12月20日起出现双耳蛙鸣样耳鸣伴进行性听力下降,3周后出现双侧颞枕部持续性针刺样剧烈疼痛.2009年1月18日突发口角歪斜,进食时右口角漏液,无视物成双、饮水呛咳及肢体麻木、乏力,拟诊"多脑神经病变"收治入院.既往体健,否认冶游史.入院体检:意识清楚,智能正常,右侧角膜反射迟钝,右侧周围性面瘫,双耳神经性聋,余脑神经及四肢运动共济、感觉检查均正常,颈软,脑膜刺激征(-).
脑栓塞是常见的卒中类型(约占10%~20%),碘油相关性脑栓塞(lipiodol brain embolism,LBE)却非常罕见.绝大多数LBE为经导管肝动脉化疗栓塞(hepatic transcatheter arterial chemoembolization,TACE)治疗肝癌过程中或延后发生.TACE治疗病史、关联性临床表现及特征性神经影像学表现对本病的诊断有重要意义[1,2].本文报道新近诊断的1例LBE病例并结合目前已有病例报道对该病进行详细阐述.
Aim:To investigate the clinical manifestation and neuro-imaging changes of infarction in the territory of anterior cerebral artery(ACA) to guide the clinical work.Methods:The clinical data of 22 patients who were diagnosed ACA infarction were analyzed.Among them,cognitive functions were examined in 12 patients using Mini-Mental State Examination(MMSE) or Montreal Cognitive Assessment Beijing Version (MoCA).Results:In the 22 ACA infaction patients,corpus callosum(n=16) and interior side of frontal lobe (n=16) were most frequently affected.The most common symptom was motor dysfunction(n=20),in which leg weakness dominant hemiparesis(n=7) and leg monoparesis(n=4) were the main form.Other manifestations include hypobuli/indifference(n=12),urinary disorder(n=10),sensory defect(n=7) and aphasia(n=3).Among the 12 patients whose cognitive functions were examined,8 persons showed cognitive dysfunction. Conclusion:There are various clinical features of ACA infarction,and identifying this particular territory of brain infarction should be careful.
BACKGROUND:Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats.METHODS:With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses.RESULTS:Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds).CONCLUSION:Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.
Objective To investigate the effect of curcumin on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptor-mediated calcium influx in cultured rat hippocampal neurons. Methods The hippocampal neurons from SD rat embryos (17 days old) were cultured for 9 days, and fluorescent calcium chelator and confocal microscopy calcium imaging were used to observe the changes in intracellular free calcium in the neurons following stimulation with 100 μmol/L KA. The effect of curcumin pretreatment at different concentrations (10, 30, 50, 100, 200 and 300 μmol/L) for 30 min on 100 μmol/L KA-induced intracellular calcium changes in the neurons were evaluated, and the effect of 15 μmol/L curcumin on intracellular calcium in the neurons stimulated with 10, 30, 50, 100, 200 and 300 μmol/L KA were also assessed. Cobalt staining was used to examine the expression of calcium permeable AMPA/KA channel in the hippocampal neurons treated with 30 and 100 μmol/L KA. Results Curcumin pretreatment at different concentrations for 30 min significantly relieved the elevation of flee calcium concentration induced by 100 or 30 μmol/L KA (P<0.05), and the effect was especially obvious with 15 μmol/L KA curcumin. Both 30 and 100 μmol/L KA increased the ratio of cobalt staining-positive hippocampal neurons, and curcumin pretreatment at 15 μmol/L, but not at 5 or 30 μmol/L, significantly reduced the ratio of the positive neurons (P<0.05). Conclusion Curcumin at appropriate concentrations can modulate calcium influx mediated by AMPA and KA in cultured rat hippocampal neurons, which might be one of the anti-epileptic mechanisms of curcumin
Objective To observe the dynamic changes of estradiol(E2)and pregnenolone (PREG)levels in serum and hippocampus of female rats with epilepsy and explore the relationship between E2 level in the hippocampus and severity of seizure. Methods The seizure model was established by injecting kainite(KA)into the hippocampus of amygdala-kindled rats.The behaviors at the moment of epileptic seizure were observed and serum and hippocampus samples were collected at 0,1,2,3,4,5,6,12 and 24 h after seizure.Rats in the control group was injected the same volume of saline at the sanle time points.The levels of E2 and PREG in the Seizure and control groups were measured by radioimmunoassay and enzyme linked immunosorbent assay,respectively.These results were statistically analyzed. Results Epileptic Seizure was showed after KA injection 5 to 10 min with the strongest seizure appearing at 3 h.The level of E2 was not significantly different in serum of the rats with epileptic seizure.While the level of E2 significantly changed in the hippocampal tissue after seizure:it elevated 1h after epileptic seizure,peaked at 4 h and returned to normal at 12 h;statistically significant differences of E2 level in the hippocampai tissue was showed among different time points(P<0.05).Besides,the E2 level in the hippocampus was increased gradually with the aggravation of the seizure(R~2=0.646,P<0.05).No significant differences were found in the PREG level of the hippocampal tissues between the rats treated with KA and the rats in the control group. Conclusion Epileptic seizure can induce local E2 synthesis in the rat hippocampus,thus,the E2 level in the hippocampus and severity of seizure is positively correlative.
缺血性脑卒中二级预防策略是建立脑卒中医疗体系的重要组成之一.其主要措施包括生活方式调整(如饮食、锻炼和戒烟)、管理可干预危险因素(如高血压、糖尿病、血脂异常和心房颤动)、抗血栓治疗(抗血小板和抗凝)和外科手术(如颈动脉内膜切除术和血管内支架置入)[1].虽然已制定了相应的标准和指南,但最近完成的药物临床试验仍可作为临床指南修订的证据补充,也为临床决策的实施提供参考.
bjective:To introduce a novel and highly efficient method of electroporation hased gene transfection into the cul- tured hippocampal neurons.Methods:Primary embryonic day 17 rat hippocampal tissues were obtained,and dissociated until homogeneously dispersed in the media.Following dissociation,the suspension was centrifugated.The supernatant was aspi- rated and the ceils were re-suspended in 100μl Rat Neuron Nucleofector(tm) solution (Amaxa Biosystems) followed by addition of 2μg of CAG-RE plasmid.The mixture of cells,Nucleofector(tm) solution and cDNA were transfered to a 2 mm electropo- ration cuvette inserted in the Nucleofector(tm).Program O-03 was used for transfecting the cells.Immediately after transfec- tion,cells were plated into the dishes with the cultured medium at densitiy of 1.0×10~5cells/cm~2.Changed the medium 4 hours later,ells were observed with fluorescent microscope in different time after transfection.Results:Neurons grew well.The ex pression of gene could be observed 24 hours after transfection until 2 weeks.The efficiency of transfection was about 60% 80%.Conclusion:Nucleofection provides the possibility for a fast and efficient method for cDNA delivery and gene function in cultured hippocampal neurons.
Wilson病,亦称肝豆状核变性,是少数可治性、常染色体隐性遗传铜代谢障碍性疾病[1],exon8是突变热区之一,首发症状多样,常累及肝、脑、肾、骨骼等,易延误诊治.在我们近200例患者资料中,仅1例表现为肝占位而行手术探查,现报告如下.
<正> 高胆固醇血症与动脉粥样硬化密切相关,是冠心病的重要危险因素之一。并非所有流行病学资料一致提示高胆固醇血症与缺血性卒中呈正相关,但近期大规模临床试验为我们提供了他汀类药物在卒中一级预防中的循证医学证据。一、高胆固醇血症与卒中流行病学尽管高胆固醇血症与卒中关系尚存在争议,但总体认为是缺血性卒中的重要危险因素之一。哥本哈根城市心脏研究对19698例受试者随访10年,结果支持胆固醇水平与
Although current epidemiological studies have not demonstrated that there is an association between serum cholesterol concentration and stroke, the effect of statins has been confirmed in the high-risk (mainly coronary heart disease, diabetes or hypertension) and advanced-age populations in the primary prevention studies. Statins have a good safety profile, and they do not increase the risk of intracerebral hemorrhage. The effect of statins in the secondary prevention of ischemic stroke remains to be confirmed by the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study.