大鼠脑缺血-再灌流后脑内MPO活性变化及组织损伤病理进观察

目的 :通过测定大鼠局灶性脑缺血 -再灌流后不同时点脑组织中 MPO活性变化 ,探讨炎症反应与脑缺血 -再灌流损伤的关系。方法 :用线栓法制备大鼠大脑中动脉缺血 -再灌流模型 ,检测缺血 3小时后再灌流不同时点脑组织中 MPO活性、脑梗死体积及光镜病理学变化。结果 :缺血组脑组织有 MPO活性升高、中性粒细胞浸润 ,以再灌流后 4 8、 72小时最为明显 ,脑梗死体积、神经元变性程度随再灌流时间延长而加重。结论 :局灶性缺血脑组织中MPO活性与缺血 -再灌流损伤间具有一定的关系 ,炎症反应是加重脑组织损伤的重要因素。     

局灶性脑缺血耐受和星形胶质细胞反应

目的　研究短暂性局灶性脑缺血预处理对永久性局灶性脑缺血的保护作用 ,及最佳预处理时间剂量 ,并探讨星形胶质细胞在脑缺血耐受中的反应。方法　采用开颅方法阻断大鼠大脑中动脉 ,通过观察大鼠脑梗死后神经功能损伤状况、脑梗死体积分析及病理形态学变化 ,评价不同的缺血预处理时间剂量 (10分钟、2 0分钟、30分钟 )对永久性局灶性脑缺血的保护作用。采用胶质纤维酸性蛋白 (GFAP)免疫组化法观察星形胶质细胞在脑缺血耐受中的反应。结果　与对照组相比 ,缺血预处理 2 0分钟未引起明显的神经元损伤 ,但使永久性局灶性脑缺血后神经功能损伤减轻 ,梗死体积明显减小 (P <0 .0 1)。免疫组化显示 ,2 0分钟缺血预处理组及重复缺血组星形胶质细胞在损伤预处理侧广泛激活。结论　 2 0分钟局灶性脑缺血预处理能够有效诱导脑缺血耐受。星形胶质细胞的激活可能与脑缺血耐受中神经元的存活相关。     

升压治疗局灶性脑缺血再灌注损伤的时间窗研究

目的　探讨升压治疗对局灶性脑缺血的保护作用及治疗时间窗。方法　采用大鼠局灶性脑缺血再灌注模型 ,30只大鼠随即分为 6组 :对照组、缺血即刻升压、缺血 1h升压、缺血 2h升压、缺血 3h升压、缺血 4h升压。观察血脑屏障破坏程度、脑梗死体积的情况。结果　缺血后 3h、4h升压后脑梗死体积与对照组分别为 4 0 9.96± 79.34mm3 、4 13.13± 6 8.14mm3 、4 10 .8± 87.6 9mm3 无统计学差异 (P >0 .0 5 ) ,且血脑屏障破坏程度明显大于对照组。结论　缺血 3h再灌注时 ,升压时间窗不超过 2h。     

胰岛素对大鼠局灶性脑缺血再灌注损伤的保护作用

目的 :研究胰岛素对脑缺血再灌注损伤的保护作用。方法 :用线栓法建立大鼠脑缺血再灌注模型 ,按胰岛素不同给药时间分为 4组 ,检测各组不同时限的血糖、神经功能缺陷评分以及梗死灶体积 ,并在电镜下对缺血边缘区进行超微结构观察。结果 :在 6h内给予胰岛素治疗 ,可使神经功能缺陷评分显著降低 ,梗死灶体积明显缩小 ,缺血边缘区超微结构损伤明显减轻。结论 :在有效治疗时窗内 (6h) ,胰岛素可明显减轻脑缺血再灌注损伤     

大鼠局灶脑缺血酪氨酸激酶B表达图像分析

目的 观察局灶脑缺血大鼠酪氨酸酶B(TrkB)阳性神经元的表达,探讨脑缺血损伤与TrkB的关系。方法 制作大鼠局灶脑缺血模型,应用免疫组化方法观察不同缺血时间、不同脑区TrkB阳性神经元数的动态改变,并进行图像分析。结果 正常脑组织内即存在着一定数量的TrkB阳性神经元,脑缺血损伤后,在额、顶叶皮质及尾壳核外侧部的变性坏死区中心,TrkB阳性神经元缺失,而变性坏死区周边的半暗带区TrkB阳性神经元自缺血6h开始明显增多,且持续于整个缺血期。其它部位TrkB表达也不同程度增强。方差分析显示,与正常对照组比较,除假手术组外(P>O.05).缺血组各组均差异显著(P<0.01)。结论 脑缺血损伤后TrkB的表达有显著改变,考虑与神经元的损伤修复机制有关。     

升压联合亚低温治疗对局灶性脑缺血再灌注的脑保护作用

目的　观察升压联合亚低温治疗对大鼠局灶性脑缺血再灌注的脑保护作用。方法　 32只大鼠随机分为对照组、升压组、亚低温组、升压 亚低温组 ,采用大鼠局灶性脑缺血再灌注模型 ,观察各组神经功能缺损评分和脑梗死体积。结果　升压组、亚低温组及升压 亚低温组神经功能缺损评分 (P <0 .0 5 )、脑梗死体积 (P <0 .0 1)均明显低于对照组 ;升压 亚低温组脑梗死体积明显低于升压组和亚低温组 (P <0 .0 5 )。结论　升压、亚低温对局灶性脑缺血再灌注损伤有明显脑保护作用 ,升压联合亚低温应用效果更佳     

大鼠局灶性脑缺血损伤中IGF-I mRNA表达

目的　观察局灶性脑缺血损伤中 IGF- I m RNA的表达特点 ,探讨其调控机制。方法　采用自体血凝块注入颈内动脉的方法制作大鼠局灶性脑缺血 2 h、4 h、6 h、12 h、2 4 h、4 8h模型 ,应用原位杂交及 RT- PCR方法 ,检测缺血中心区及半暗带区 IGF- I m RNA的表达。结果　局灶性脑缺血损伤时 ,缺血中心区及半暗带区 IGF- I m R-NA表达增加 ,尤以缺血半暗带区增加明显。结论　 IGF- I对局灶性脑缺血损伤具有保护作用。     

依达拉奉对大鼠局灶性脑缺血Caspase-3、Bcl-xl表达的影响

目的探讨依达拉奉对局灶性脑缺血损伤过程中脑细胞Caspase-3、Bcl-xl表达的影响及其机制。方法采用光镜、免疫组化方法检测大鼠局灶性脑缺血后梗死体积、病理变化及不同时间Caspase-3、Bcl-xl表达,应用依达拉奉对上述指标进行干预。结果局灶性脑缺血时Caspase-3、Bcl-xl的表达水平呈动态变化,Caspase-3表达于缺血24h达高峰,Bcl-xl表达于缺血6h达高峰,依达拉奉可使Caspase-3表达下降,Bcl-xl表达增加;依达拉奉能明显减小缺血后24h的梗死体积,减轻神经细胞损伤。结论依达拉奉干预可使脑缺血后Caspase-3表达减弱,Bcl-xl表达增强,缩小梗死体积,从而减轻神经元损伤。依达拉奉调整Caspase-3、Bcl-xl蛋白表达变化,可能是其脑保护作用机制之一。     

牛磺酸对大鼠局灶性脑缺血-再灌注损伤的全脑保护作用

目的探讨牛磺酸(Tau)对局灶性脑缺血—再灌注损伤全脑保护作用。方法应用血栓栓塞法制作大鼠短暂性局灶性脑缺血—再灌注动物模型。应用苏木精—伊红染色方法研究神经元核周体损伤。应用免疫组组化学方法检测大鼠类淀粉样前体蛋白(APP)和微管相关蛋白tau—1表达,定量研究轴突和少突胶质细胞损伤。结果牛磺酸能减小局灶性脑缺血—再灌注后神经元核周体损伤体积(P<0.01),保护灰质。牛磺酸能减小局灶性脑缺血—再灌注后缺血侧脑组织总的APP分数(P<0.01)和含tau—1免疫反应阳性少突胶质细胞体积(P<0.01),对轴突和少突胶质细胞有保护作用。结论牛磺酸可减轻局灶性脑缺血—再灌注时脑缺血区灰质和白质的损伤,对局灶性脑缺血—再灌注损伤具有全脑保护作用。     

棓丙酯对大鼠急性脑缺血再灌注损伤的保护作用

目的探讨棓丙酯注射液对大鼠急性脑缺血-再灌注损伤的保护作用及其可能机制。方法采用线栓法制备大鼠右侧大脑中动脉栓塞所致的缺血-再灌注模型。观测神经功能学评分、脑梗死面积、光镜和电镜下形态结构、超氧化物歧化酶活性及丙二醛含量变化。结果与模型组相比,棓丙酯注射液能降低大鼠急性脑缺血-再灌注后神经功能学评分、梗死面积、缺血区脑组织MDA含量,并且能够减轻脑组织形态学和超微结构损伤、升高SOD活性。结论棓丙酯注射液对大鼠急性局灶性脑缺血-再灌注损伤有保护作用,其机制可能与升高SOD活性、清除自由基有关。     

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.     

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.     

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.     

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.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.