MSCTA及DSA对模型兔颈动脉狭窄的评价

目的 探讨多层螺旋CT血管造影术(MSCTA)及数字减影血管造影术(DSA)对粥样硬化性颈动脉狭窄模型兔的诊断价值.方法 30只兔中的10只做为空白对照组,余20只兔颈动脉外膜置人改良的硅胶橡胶圈后,给予兔高胆固醇饲料喂养2周诱导颈动脉狭窄模型兔,采用股动脉插管方法行MSCTA及DSA检查,观察模型兔颈动脉狭窄程度及影像学征像,比较二者对颈动脉粥样硬化性狭窄的诊断价值.结果 MSCTA及DSA均可显示颈动脉管腔狭窄的部位、范围、程度及形态以及颈动脉的血管走向,MSCTA对颈动脉狭窄敏感程度较高,但对颈动脉狭窄的特异性诊断不如DSA.结论 MSCTA和DSA能较好的反应模型兔的颈动脉狭窄部位、形态.     

颈动脉粥样硬化斑块中COX-2、mPGES-1表达及塞来昔布对其的影响作用

目的探讨兔颈动脉粥样硬化斑块中环氧化物酶-2（COX-2）、诱导型前列腺素合成酶-1（mPGES-1）的表达机制及塞来昔布对其表达的影响。方法采用32只雄性新西兰大白兔．其中正常对照组8只（A组），另24只将特制的硅橡胶圈置于兔右侧颈动脉。术后给予1％高胆固醇喂养14d，建立兔颈动脉粥样硬化性狭窄动物模型，将模型兔随机分为颈动脉狭窄无干预组（B组1、小剂量塞来昔布治疗组（15mg／kg，C组），大剂量塞来昔布治疗组（35mg／kg，D组），每组各8只。治疗4周后取双侧颈动脉并分为平等2段，分别行半定量逆转录聚合酶链反应（RT—PCR）及Western blot法测定颈动脉斑块干预后COX-2及mPGES-1的表达。结果与A组比较,B、C、D组颈动脉粥样硬化模型兔的斑块中COX-2及mPGES．1表达增高，差异具有显著性（P〈0．05）；与B组比较，C、D组颈动脉斑块的C0X-2及mPGES．1表达显著下调，差异有显著性（P〈0．051。结论在颈动脉粥样硬化斑块的病理过程中炎症反应可能起着主导作用。塞来昔布干预可抑制COX-2及mPGES—1的表达，减缓颈动脉粥样硬化的进展。     

颈动脉粥样硬化斑块ABCA1表达及辛伐他丁干预的影响

目的 探讨模型兔颈动脉粥样硬化斑块三磷酸腺苷结合盒运转体A1（ATP bindingcassette A1,ABCA1）、视黄酸X受体（Retinoid X recepter,RXRα）表达机制及辛伐他丁对其表达的影响.方法 32只新西兰大白兔,分为4组,空白对照组8只（A组）,余24只于兔右侧颈动脉放置改良的硅橡胶圈加1%高胆固醇喂养的方法建立粥样硬化斑块性颈动脉狭窄动物模型.颈动脉狭窄模型无干预对照组8只（B组）;小剂量辛伐他丁治疗组8只（辛伐他丁每天2.5mg/kg每天1次;C组）;大剂量辛伐他丁治疗组8只（辛伐他丁5mg/kg,每日1次,D组）.辛伐他丁干预前后检测兔模型静脉血的TG、TC、LDL及HDL水平,干预4周后处死动物取右侧颈动脉狭窄段及对侧相应段血管,以WesternBlot法测定其ABCA1、RXRα蛋白质表达量.结果 与A组比较,B、C、D组的ABCA1、RXRα蛋白质表达水平下调（P＜0.05）;辛伐他丁治疗4周后,与B组比较,C、D组ABCA1、RXRα蛋白质表达水平均有所上调（P＜0.05）;与C组比较,D组的ABCA1、RXRα蛋白质表达水平下调无统计学意义（P＞0.05）;与B组比较,C、D组的血脂水平显著下降（P＜0.05）.结论 ABCA1、RXRα蛋白表达下调可能参与颈动脉粥样硬化形成的机制,辛伐他丁可能通过上调ABCA1、RXRα蛋白质表达的机制,而有益于抗动脉粥样硬化斑块形成作用.     

高脂喂养加干燥气体损伤构建颈动脉狭窄动物模型

目的探讨建立经济实用、稳定可靠的适合颈动脉粥样硬化性狭窄外科治疗研究的动物模型的条件。方法日本大耳白兔40只,采用血管内膜气体干燥损伤法在动物的颈总动脉上造成特定条件的损伤(160ml/min×15min),然后以特定高胆固醇饲料(饲料中含2%的胆固醇和6%的花生油)喂养动物不同时间(30天,60天和90天)。通过血脂测定、DSA、HE染色方法评价各组动物血管狭窄程度,再观察其病理改变特点。结果病理检查证实:随着喂养时间的延长,动脉粥样硬化程度在加重,高脂喂养加干燥气体损伤90天时,血管狭窄率达71.53±3.65%,动脉的粥样硬化病理改变已属十较成熟的粥样斑块期。结论按本实验方法,90天时颈动脉狭窄程度和病理改变程度符合颈动脉粥样硬化性狭窄外科治疗之实验研究需要。     

利舒康对兔颈动脉斑块中COX-2 mRNA表达的影响

目的探讨利舒康对兔颈动脉斑块中COX-2mRNA表达的影响。方法选取32只雄性新西兰大白兔,其中正常对照组8只(A组),24只硅橡胶圈兔颈动脉粥样斑块的动物模型。将模型兔随机分为颈动脉斑块无干预组(B组)、小剂量利舒康治疗组(50mg/kg,C组),大剂量利舒康治疗组(400mg/kg,D组),每组8只。治疗4周后取双侧颈动脉并分为平等2段,采用实时荧光定量PCR(RT-qPCR)技术检测A、B、C、D组COX-2mRNA的相对表达量。结果与A组比较,B组颈动脉粥样硬化模型兔的斑块COX-2mRNA表达增高,差异有统计学意义(P0.05);与B组比较,C、D组颈动脉斑块COX-2mRNA表达明显下调,差异有统计学意义(P0.05)。结论利舒康的干预下兔颈动脉粥样斑块的COX-2mRNA下调,有可能具有抗动脉粥样硬化的炎性反应作用。     

脑梗死患者血清ESM-1表达水平与颈动脉粥样硬化性狭窄的关系

目的 探讨脑梗死患者血清ESM-1表达水平与颈动脉狭窄关系。方法 选取79例CI患者作为CI组,49例无(CI)患者为无脑梗死组,根据颈动脉粥样硬化性狭窄程度将受试者分为4个亚组,比较各亚组间血清ESM-1水平差异有统计学意义。结果 随着颈动脉粥样硬化性狭窄程度的逐渐增加,血清ESM-1表达水平也随之逐渐升高。结论 血清ESM-1表达水平与颈动脉粥样硬化性狭窄程度存在正相关性。     

家兔颈动脉粥样硬化模型的建立

目的寻找一个建立家兔颈动脉粥样硬化模型的简单、重复性好的方法.方法 35只日本大耳白兔随机分成3组:正常组5只,高脂喂养组15只和高脂喂养加手术组15只.正常组普通饲料喂养,高脂喂养组给予高脂喂养,高脂喂养加手术组喂养1周后行颈动脉空气干燥术,并分别在喂养2、4、6周行脑血管DSA和观察颈动脉粥样硬化的病理变化.结果喂养4、6周时就可以形成颈动脉粥样硬化的病变,DSA可以发现颈动脉狭窄,内膜中膜比(I/M):1.05±0.008(喂养4周时),1.11±0.007(喂养6周时).结论利用高脂喂养加颈动脉空气干燥法可以建立一种成熟的颈动脉粥样硬化模型,而且此方法简单、重复性好,有利于进行颈脉粥样硬化的实验研究.     

颈动脉狭窄动物模型的构建及核因子-κB和胰岛素样生长因子-1的表达

目的 探讨建立经济实用、稳定可靠的适合颈动脉粥样硬化性狭窄外科治疗研究的动物模型的条件.通过测量核因子(NF)-κB、胰岛素样生长因子(IGF)-1的表达,探讨它们在颈动脉粥样硬化性狭窄发生、发展中的作用.方法 日本大耳白兔40只,采用血管内膜气体干燥损伤法在动物的颈总动脉上造成特定条件的损伤(160 ml/min×15 min),然后以特定高脂饲料(饲料中含2%的胆固醇和6%的花牛油)喂养动物不同时间(30、60和90 d).通过血脂测定、DSA、HE染色评价各组动物血管狭窄程度,再观察其病珲改变特点.应用免疫组织化学方法观察NF-KB和IGF-1在动脉粥样硬化斑块中的表达特点.结果 病理检查证实:随着喂养时间的延长,动脉粥样硬化程度加重,高脂喂养加干燥气体损伤90 d时,血管狭窄率达71.53%±3.65%(q=568.417,P=0.000),动脉的粥样硬化病理改变已属较成熟的粥样斑块期.正常血管的内膜和中膜内均未见明显的NF-κB和IGF-1的表达,模型组血管斑块内NF-κB、IGF-1表达呈强阳性,表达面积分别为59.66%±12.04%(t=22.98,P＜0.01)、54.48%±12.92%(t=5.76,P＜0.01),明显高于对照组(分别为8.34%±2.66%和16.38%±8.22%).结论 按本实验方法,90 d时颈动脉狭窄程度和病理改变程度符合颈动脉粥样硬化性狭窄外科治疗的实验研究需要.NF-κB及其靶基因IGF-1的激活与动脉粥样硬化病变的发生和发展密切相关,在颈动脉粥样硬化斑块形成过程中发挥重要作用.     

颈动脉粥样硬化性狭窄动物模型的建立

目的 探讨建立经济实用、稳定可靠的适于颈动脉粥样硬化性狭窄(CASS)外科治疗研究的CASS动物模型的条件。方法 新西兰白兔25只，采用血管内膜气体干燥损伤法在动物的颈总动脉上造成特定条件的损伤，然后以特定高脂饲料喂养动物不同时间。评价各组动物血管狭窄程度和病理改变特点。结果 1月组、2月组和3月组各组中重度狭窄均达到80％。病理检查证实高脂喂养2个月时，动脉的粥样硬化病理改变已属于较成熟的纤维斑块期。结论 按本实验方法，损伤后喂养2个月的动物颈动脉狭窄程度和病理改变程度皆符合CASS外科治疗之实验研究需要。     

小檗碱对家兔颈动脉粥样硬化干预的实验研究

目的　探讨小檗碱对家兔颈动脉粥样硬化形成的干预作用。方法　2 4只日本大耳白家兔随机分成正常组、对照组和小檗碱干预组,正常组8只,普通饲料喂养5周;对照组8只,高脂喂养一周后行颈总动脉内膜空气干燥术,术后继续喂养4周;小檗碱干预组8只,高脂喂养一周后行颈总动脉内膜空气干燥术,术后继续高脂喂养并每日肌肉注射小檗碱,剂量为5 mg/ kg,时间为4周。实验满5周后,行右侧脑血管造影(DSA)术并观察正常组、对照组和小檗碱干预组的颈动脉的病理变化和计算内膜中膜比(I/ M)。结果　正常组的颈动脉的内膜围一层单皮细胞,中膜为规则的平滑肌肌层;对照组内膜明显增厚,中膜变薄,HE染色可见大量泡沫细胞堆积和坏死的物质;小檗碱干预组内膜也有增厚的现象,增厚程度明显小于对照组,HE染色见有泡沫细胞形成,堆积程度小于对照组。DSA发现对照组的颈动脉有不同程度的狭窄,而小檗碱预防组的家兔没有发现明显的颈动脉狭窄。结论　小檗碱可以干预家兔颈动脉粥样硬化的形成过程,延缓粥样硬化的发生。     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.