脑积水对脑室周围神经干细胞影响的实验研究

目的探讨脑积水对大鼠脑室周围神经干细胞影响。方法6wWistar大鼠70只，随机分为实验组35只，对照组35只，应用显微外科技术向枕大池内注入25％无菌高岭土混悬液0．05ml，分别在高岭土注射后3d，1w，2w，3w，4w处死动物，迅速取脑组织，测侧脑室指数，用免疫组织化学方法动态检测脑室周围Nestin阳性细胞的表达，同样方法向枕大池内注入生理盐水作为对照组。结果实验组28只大鼠成功诱发脑积水并完成实验全过程，对照组30只完成实验全过程。对照组大鼠各对应时间点，侧脑室指数基本相同，实验组大鼠脑室进行性扩大；脑室周围Nestin阳性细胞：对照组细胞数平均193±20．3个并维持，脑积水造模后3d达到最大值，为对照组308％±1％（P〈0．001），1w脑室周围Nestin阳性细胞下降到对照组196％±1％，2w降到对照组水平210±22．4个，3w脑室周围Nestin阳性细胞几乎看不到并持续。结论脑积水引起脑室进行性扩大，脑室周围神经干细胞可能受脑室扩张机械性压迫引起缺血，缺氧影响，参与脑积水病理损害和修复过程。     

米诺环素对脑积水大鼠星形细胞增生的影响

目的 研究米诺环素对脑积水大鼠星形细胞增生的影响.方法 成年雄性SD大鼠100只,应用显微外科技术向枕大池内注入25％无菌高岭土混悬液0.1ml诱导脑积水.取75只造模成功大鼠随机分为实验组和对照组,实验组再分为5个亚组(3、7、14、21、28 d),每个亚组10只,配对对照组5只大鼠.分别于术后3、7、14、21和28 d行MRI检查.实验组给予米诺环素,对照组给予等量生理盐水.Morris水迷宫实验后取脑组织行苏木精-伊红染色、胶质纤维酸性蛋白(GFAP)免疫组化检查.结果 不同时间组脑积水大鼠室周白质和海马中均出现GFAP阳性星形细胞.实验组脑积水大鼠GFAP阳性星形细胞数目明显少于对照组(均P ＜0.01).两组Morris水迷宫实验差异无统计学意义(P＞0.05).结论 米诺环素对脑积水大鼠室周白质和海马星形细胞活化增生具有抑制作用.     

大鼠脑积水模型的建立

目的建立一种成年大鼠脑积水动物模型。方法雄性Wistar大鼠60只，随机分为实验组和对照组，其中实验组48只，再随机平均分为A、B、C．D四个亚组，应用显微外科技术向枕大池内注入25％白陶土混悬液0．1mL，分别在白陶土注射后第1、2、4、6周行MRI检测，鉴定脑积水是否形成，并测定第三脑室层面侧脑室大小。对照组12只用同样方法向枕大池内注人生理盐水0．1mL，2周后行MRI检测。并行病理切片检查。结果实验组有34只大鼠成功诱发脑积水，且脑室随着时间的延长而逐渐扩张。结论白陶土注射法可以制作确切的大鼠脑积水模型，特别适用于急慢性脑积水的研究。     

转化生长因子β1在交通性脑积水中的表达

目的 研究转化生长因子β1(transforming growth factor-β1,TGF-β1)在高岭土诱导大鼠脑积水模型中的表达及意义.方法 将40只Wistar大鼠随机分为两组,Kaolin组:枕大池中注射2%高岭土50μl,造成交通性脑积水模型;Saline组:枕大池中注射生理盐水50μl(阴性对照组).结果 注射后28 d,Kaolin组的脑室扩张程度,颅内软脑膜纤维化程度以及脑脊液中TGF-β1含量均比Saline组明显增高.结论 TGF-β1的高表达与交通性脑积水的发生及发展有关.     

实验性脑积水脑能量代谢的研究

1．建立脑积水模型：重10～15kg成年健康雄性脑室正常20条杂种狗，随机分为对照组、诱导后3d、8d、4个月4组，各5条。速眠新肌注全麻，穿刺枕大池，注入无菌25％高岭土悬浊液0．3ml／kg诱导脑积水，CT检查证实。     

VEGF在实验性脑积水大鼠脑组织中的表达

目的 探讨血管内皮生长因子（VEGF）在脑积水后脑组织中的表达状况。方法 雄性Wistar大鼠60只，随机分为实验组和对照组，其中实验组48只，再随机平均分为A、B、C、D四个亚组，应用显微外科技术向枕大池内注入25％白陶土混悬液0．1ml，分别在白陶土注射后第1、2、4、6周行MRI检查，获取鼠脑冠状切面的T2图象，鉴定脑积水是否形成。之后24h内处死动物并迅速取脑组织，应用免疫组织化学方法分别测定各组大鼠脑组织不同部位VEGF表达情况。其余12只用同样方法向枕大池内注入生理盐水作为对照组。结果 34只大鼠成功诱发脑积水。与对照组相比，实验组脑组织中VEGF表达均明显升高，尤其是脑室周围白质更为明显。结论 VEGF可能参与脑积水的病理损害和恢复过程。     

大鼠实验性脑室出血后水通道蛋白1在脑内的表达及意义

目的 观察大鼠脑室出血后水通道蛋白1(AQP1)在大鼠脑内的表达变化,探讨其与脑出血后慢性脑积水之间的关系. 方法 将45只Wister大鼠按照随机数字表法分为3组:正常对照组(5只,不作任何处理)、假手术对照组(20只,侧脑室内注入0.1 mL生理盐水)、实验组(20只,侧脑室内注入0.1 mL枸橼酸化的自体静脉血),后2组再分别分为术后3 d、7 d、14 d、30 d4个时相点,每时相点5只.分别采用免疫组化、原位杂交方法观察大鼠脑室出血后不同时间AOP1蛋白及AQP1 mRNA在大鼠脑内的表达变化. 结果 实验组30 d时相点4只大鼠出现脑积水(4/5)、其余组别未出现慢性脑积水.正常对照组大鼠AQP1蛋白在脉络丛上皮细胞顶质膜强烈表达,室管膜、纵裂池、软脑膜、蛛网膜、硬脑膜也有较强烈表达;实验组大鼠脑室出血后3 dAQP1蛋白表达减少,7 d表达继续减少,14 d表达最弱,与正常对照组、假手术对照组比较,差异均有统计学意义(P<0.05),30d表达仍较弱.大鼠AQP1 mRNA在脑内的表达强度较AQP1蛋白弱,表达部位及变化与AQP1蛋白基本一致. 结论 AQP1作为水通道蛋白不仅参与脑脊液的分泌,可能也参与脑脊液的循环吸收过程;大鼠实验性脑室出血后AQP1表达下调导致脑脊液吸收减少可能也参与脑出血后慢性脑积水的形成.     

大鼠脑室出血后急性期脑损伤病理特点的初步探讨

目的 初步探讨大鼠脑室出血后急性期脑损伤的病理特点. 方法 健康成年雄性SD大鼠38只按随机数字表法分为对照组和脑室出血组,分别采用立体定向技术向右侧脑室内注入生理盐水200 μL或自体股动脉血200 μL手术建模.术后24 h观察大鼠体质量减轻情况,采用小动物Micro-CT扫描及大体标本脑室切面观察脑室铸型;采用干湿重法测定术后24 h大鼠脑组织含水量;采用伊文思蓝染色法(24 h时)和IgG免疫荧光染色法(48 h时)观察大鼠血脑屏障损伤情况.结果 术后24 h时脑室出血组体质量减轻(5.29％±0.59％)明显高于对照组(3.36％±1.10％),差异有统计学意义(P＜0.05).脑室出血组Micro-CT扫描及脑室切面可见脑室积血铸型并明显扩张.脑室出血组双侧大脑半球脑组织含水量(左侧:78.25％±0.29％;右侧:78.46％±0.21％)均明显高于对照组(左侧:77.64％±0.25％;右侧:77.91％±0.10％),差异有统计学意义(P＜0.05).术后24 h时脑室出血组伊文思蓝脑组织渗出量明显高于对照组,48h时脑室出血组侧脑室脉络丛免疫球蛋白IgG表达明显高于对照组. 结论 脑室出血后脑损伤除脑积水外还存在急性脑水肿、血脑屏障损伤等病理损害,其可能是脑室出血后除继发脑积水外急性脑损伤的重要环节.     

猪实验性脑室出血后慢性脑积水模型的建立及蛛网膜下腔脑脊液循环的改变

目的建立猪实验性脑室出血后慢性脑积水动物模型,对脑出血后慢性脑积水的发生机制进行初步研究。方法雌性贵州小型猪20只,健康对照组5只、实验组15只。实验组分别将15ml(1只)、12ml(1只)、8ml(13只)枸橼酸化的自体静脉血注入侧脑室内建立猪实验性脑室出血后慢性脑积水动物模型;健康对照组不作处理。采用MRI动态观察脑室变化,SPECT观察蛛网膜下腔CSF循环的改变,观察病理及超微结构改变。结果健康对照组死亡1只(1/5)、实验组死亡4只(4/15)。实验组脑室出血后30d有7只(7/11)形成慢性脑积水;健康对照组未出现脑积水。脑室出血后各时相点蛛网膜下腔核素显影均局限在椎管穿刺点附近,显示CSF循环障碍持久存在;脑室出血后蛛网膜下腔轻度增宽、蛛网膜细胞间隙纤维样结构增多,未形成脑积水动物的病理改变较形成脑积水者轻。结论猪脑室出血后蛛网膜下腔的CSF循环吸收障碍可能与电镜所发现的蛛网膜纤维化有关;蛛网膜纤维化可能是出血后慢性脑积水的主要形成原因之一。     

辛伐他汀抑制慢性颞叶癫痫形成的初步研究

目的 研究辛伐他汀对慢性颞叶癫痫大鼠脑组织病理改变及癫痫发作的影响.方法 成年雄性Wistar大鼠72只按照随机数字表法分为对照组、盐水组及辛伐他汀组,每组24只.对照组大鼠单侧脑室内单次注入生理盐水1 μL;盐水组大鼠单侧脑室内注入海人酸(KA)致痫成功0.5 h后,生理盐水灌胃(1 mg每公斤体质量),每日1次,连续14d;辛伐他丁组大鼠单侧脑室注入KA致病成功0.5h后,进行辛伐他汀灌胃(1 mg每公斤体质量),每日1次,连续14d.致痫后3d、4个月、5个月、6个月4个时间点处死大鼠,制作脑组织石蜡切片进行Timm's染色、Nissl染色、GFAP染色,观察慢性颞叶癫痫大鼠脑组织病理改变:同时记录大鼠的癫痫发作,参照Racince's分级法分级并计分. 结果 与盐水组相比,辛伐他丁组小鼠CA3区和齿状回的神经元丢失减少,胶质细胞增生减少,苔状纤维发芽程度明显减轻,癫痫发作级别降低,差异有统计学意义(P＜0.05). 结论 辛伐他汀在慢性颞叶癫痫的形成过程中起到了长期的神经保护作用.     

Survey of public awareness, attitudes, and understanding toward epilepsy in Nhan Chinh, Hanoi, Vietnam, in 2003

PURPOSE: Many studies have shown that cultural and social awareness of, attitudes toward, and knowledge about epilepsy can have an impact on the acceptance of treatment. The aim of this study is to characterize public awareness of attitudes toward and understanding of epilepsy in a Vietnamese community and to compare results with those obtained in other cultures. METHODS: A survey concerning the knowledge, attitudes, and practices of Vietnamese people with respect to epilepsy was carried out in the Nhan Chinh precinct of Hanoi. One thousand people were randomly selected for face-to-face interviews regarding epilepsy. RESULTS: Of the subjects surveyed, 54.6% had heard of epilepsy; 45.5% knew someone with epilepsy; 49.2% had witnessed an epileptic seizure; 56% would not allow their son or daughter to marry someone with epilepsy; 42.1% did not believe that epileptic patients could hold down a normal job; 77.8% believed that epilepsy is an organic disorder of the brain; 23.8% thought that epilepsy is a form of dementia; and 91% thought that epileptic patients require medical care. CONCLUSION: As compared with surveys conducted in other countries, our survey showed that the awareness of epilepsy in this Vietnamese community is limited, and gives rise to alternative attitudes and practices.     

Diphenylhydantoin, Phenobarbital, and Primidone in Saliva, Plasma, and Cerebrospinal Fluid

Diphenylhydantoin, primidone, and phenobarbital were determined in saliva and plasma of 164 patients by gas-liquid chromatography. The saliva ratio was about one-tenth in patients on diphenylhydantoin, 0.32-0.38 on phenobarbital alone and with other drugs, 0.97 and 0.96 on primidone alone and with other drugs. The S/P ratio of phenobarbital was similar in patients treated with primidone alone or with co-medication. For diphenylhydantoin and primidone, the S/P and CSF/plasma ratio were similar; for phenobarbital the S/P ratio was lower due to the difference in pH of saliva and CSF. Thus the concentration in saliva serves as a measure of the nonprotein-bound or free concentration in plasma with the advantage that saliva is easy to obtain. Co-medication does not change the S/P ratio for the three drugs studied. The high correlation between levels in plasma and in saliva allows the plasma levels to be predicted from the concentration in saliva.     

Ethnicity,sleep, mood,and illumination in postmenopausal women

Background  

This study examined how ethnic differences in sleep and depression were related to environmental illumination and circadian rhythms.     

Arterial antithrombotic effects of aspirin, heparin, enoxaparin and clopidogrel alone, or in combination, in the rat

INTRODUCTION: Many antithrombotic drugs may have a deleterious effect on normal haemostasis leading to bleeding complications. The aim of this study was to determine if sub-therapeutic (low) doses of antithrombotic agents, when administered in combination, have enhanced efficacy without augmentation of bleeding time. MATERIALS AND METHODS: The antithrombotic effects of i.v. aspirin (4-30 mg/kg), heparin (100-500 U/kg), enoxaparin (4-30 mg/kg) and clopidogrel (10-20 mg/kg) were studied in a rat Folts-like preparation of carotid arterial thrombosis. The frequency of cyclic flow reductions (CFRs; indicating occlusive thrombus formation) and bleeding time were measured. Drug doses that were singly ineffective at preventing occlusive thrombus formation were tested in the following combinations: aspirin (10 mg/kg) with heparin (250 U/kg); aspirin (4 mg/kg) with enoxaparin (4 mg/kg); and aspirin (10 mg/kg) with clopidogrel (10 mg/kg). RESULTS: Control period (pretreatment) CFRs were not significantly different between groups; average 7.0+/-0.3 CFRs/30 min (n=64). Tail bleeding time before drug(s) was 3.1+/-0.1 min (n=86). When administered alone, aspirin (4-30 mg/kg), heparin (250 U/kg) or enoxaparin (4 mg/kg) had no effect on CFRs or bleeding time. Heparin (500 U/kg), enoxaparin (10 and 30 mg/kg) and clopidogrel (20 mg/kg) significantly decreased CFRs. Single administration of heparin (500 U/kg) or enoxaparin (30 mg/kg) increased bleeding time by 4- or 11-fold. When co-administered, aspirin 10 mg/kg and heparin 250 U/kg decreased CFRs, but also increased bleeding time by 11-fold. However, combination of aspirin and enoxaparin (4 mg/kg each), or aspirin and clopidogrel (10 mg/kg each), decreased CFRs with no effect on bleeding. CONCLUSIONS: In a preparation of arterial thrombosis in the rat, combinations of sub-efficacious (low) doses of aspirin with enoxaparin or clopidogrel inhibited thrombus formation without augmenting bleeding time. However, low-dose aspirin combined with heparin, whilst inhibiting thrombus formation, exacerbated bleeding time. If these findings translate into the clinic, the use of effective low-dose combinations may have therapeutic advantages.     

Changes in gamma-aminobutyrate, glutamate, aspartate, glycine, and taurine contents in the striatum after unilateral nigrostriatal lesions in rats

Contents of five amino acids (gamma-aminobutyrate (GABA), glutamate, aspartate, glycine, and taurine) were assayed in the rat striatum in which nigrostriatal pathways were unilaterally destroyed by 6-hydroxydopamine. GABA content in the operated side was significantly increased 1 month after the surgery compared with that in the nonoperated side. Contents of four other amino acids assayed did not change significantly. Among possible mechanisms for this elevation we postulated that sprouting of the GABAergic terminals in the striatum would be most probable.     

Prevalence, knowledge, attitude, and practice of epilepsy in Kerala, South India

PURPOSE: To ascertain the prevalence and pattern of epilepsy and to characterize and quantify knowledge, attitude, and practice (KAP) toward epilepsy among the people of the state of Kerala, which is distinguished from the rest of India by a high level of literacy and health awareness of its population. METHODS: We conducted a door-to-door survey covering the entire population of 238,102 people residing in 43,681 households in a semiurban area of central Kerala. The screening questionnaire administered by medical social workers had a sensitivity of 100% for identifying persons with epilepsy. Neurologists examined all the individuals suspected of having epilepsy. We evaluated KAP toward epilepsy among 1,118 subjects (439 males and 679 females; mean age, 33.3 years; age range, 15-85 years) from households without epilepsy in the study area. RESULTS: Through a three-phased survey, we ascertained 1,175 cases (616 males and 559 females) with active epilepsy, providing a crude point prevalence ratio of 4.9 cases per 1,000 people and an age-adjusted prevalence ratio of 4.7 cases per 1,000 population. The highest age-specific prevalence rate of 6.5 per 1,000 occurred in the 10- to 19-year-old age group. Sex-specific prevalence rates did not significantly differ. The proportion of generalized and localization-related epilepsies was 58.8% and 30.6%, respectively. Ninety-nine percent of the KAP respondents had read or heard about epilepsy. Thirty-one percent and 27% thought epilepsy was a hereditary disorder and a form of insanity, respectively. About 40% of the respondents felt that individuals with epilepsy could not be properly educated or employed. Eleven percent would object to their children having contact with epileptic children. CONCLUSIONS: The prevalence and pattern of epilepsy in central Kerala, South India, do not differ from that of developed countries. Although the awareness of epilepsy among the people of Kerala was comparable to that of developed countries, the attitudes were much more negative. The need for educating the people of Kerala on epilepsy and for incorporating an adequate knowledge of epilepsy in the school curricula cannot be overemphasized.     

Progression in idiopathic,diabetic, paraproteinemic,alcoholic, and B12 deficiency neuropathy

We determined prospectively the clinical and electrophysiological progression of idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy in 606 subjects over 3 years. We hypothesized that idiopathic peripheral neuropathy would demonstrate slower progression when compared with other etiologies. Laboratory assessments were used to determine the etiology of peripheral neuropathy at baseline and after 3 years. When compared with peripheral neuropathy related to type 1 or type 2 diabetes mellitus, subjects with idiopathic peripheral neuropathy progressed much slower, but demonstrated similar rates of progression to that of the other groups. Overall, detectable progression was minimal over 3 years. After 3 years, only 3% of cases of idiopathic peripheral neuropathy had any potentially identifiable causes discovered. Clinical and electrophysiological detection of very slow progression for these five types of peripheral neuropathy is possible using currently established clinical scales and standard electrophysiological techniques.