丹红注射液对脑缺血再灌注损伤大鼠ICAM-1表达的影响

目的 探讨丹红注射液对脑缺血再灌注损伤大鼠ICAM-1表达和白细胞浸润的影响.方法 SD大鼠24只,随机分为假手术组(n=8)、缺血再灌注组(n=8)和bFGF组(n=8).应用线栓法制作大鼠局灶性脑缺血再灌注模型,大脑中动脉阻塞1 h再灌注损伤24 h,术前治疗组丹红注射液预处理3 d,假手术组及缺血再灌注组用生理盐水预处理,采用免疫组织化学法染色和组织HE染色检测缺血区脑微血管内皮ICAM-1的表达及白细胞计数.结果 缺血再灌注组与假手术组相比ICAM-1表达明显升高,白细胞浸润明显(P<0.05).丹红治疗组ICAM-1表达较缺血再灌注组明显减少,白细胞浸润程度减轻(P<0.05).结论 丹红注射液预处理可降低局灶性脑缺血再灌注损伤大鼠ICAM-1表达,减轻白细胞浸润,提示抑制粒细胞黏附作用是其脑保护作用机制之一.     

大鼠脑缺血再灌注模型ICAM-1表达与白细胞浸润关系及亚低温干预治疗的研究

目的　研究大鼠局灶性脑缺血再灌注后不同时程脑组织中的细胞间粘附分子 1 (ICAM 1 )表达规律 ,及其与白细胞浸润的关系 ,并探讨亚低温的治疗作用。方法　采用大鼠大脑中动脉 (MCA)线拴闭塞 /再通法建立大鼠局灶性脑缺血 再灌注模型 ,常温组分别于脑缺血 3小时再灌注 2小时、8小时、2 4小时、48小时、72小时后断头取脑 ;假手术组及亚低温组于脑缺血 3小时再灌注 2 4小时断头取脑 ,行ICAM 1免疫组化及组织HE染色 ,测定ICAM 1表达阳性微血管数及白细胞计数。结果　⑴脑缺血再灌注后 2小时 ,脑缺血的坏死周边区的微血管内皮细胞表达ICAM 1出现增高趋势 ,并于 2 4小时达到高峰 ,各组之间及各组与假手术组间均有显著差异 (均P <0 0 5) ;⑵脑缺血再灌注 8小时出现白细胞浸润 ,且浸润高峰也在 2 4小时 (P <0 0 1 ) ;⑶ICAM 1的表达与白细胞浸润呈正相关 (r =0 .82 7,P <0 0 1 ) ;⑷缺血早期进行亚低温治疗能明显减轻缺血再灌注后ICAM 1的表达及减少白细胞浸润 (P <0 0 1 )。结论　脑缺血再灌注后ICAM 1可介导白细胞和内皮细胞的粘附 ,加速白细胞的浸润 ,提示ICAM 1是造成脑缺血损伤的重要因素之一 ;亚低温的干预治疗能明显减轻缺血再灌注后脑组织病理形态学的损害程度。     

细胞间粘附分子-1在慢性糖尿病大鼠局部脑缺血再灌流损伤中的作用

目的探讨ICAM-1在糖尿病脑缺血再灌流损伤中的作用.方法采用线栓法脑缺血再灌注模型,比较糖尿病及正常大鼠缺血再灌注后脑内ICAM-1的表达、炎性细胞浸润及梗塞大小.结果糖尿病大鼠缺血再灌注组脑组织受到的缺血损害明显重于正常缺血再灌注大鼠组;糖尿病缺血大鼠脑内微血管内皮细胞ICAM-1的表达以及炎性细胞浸润程度明显高于正常缺血对照组(P＜0.05).结论糖尿病可加重局灶性脑缺血再灌流损伤并增强炎性反应的程度.超负荷血糖条件下ICAM-l可能是加重糖尿病脑缺血再灌流损伤的机制之一.     

大鼠脑缺血再灌注后ICAM-1的表达与白细胞浸润关系的研究

目的 研究大鼠局灶性脑缺血再灌注后脑组织中细胞间粘附分子－1（ICAM－1）的表达与白细胞浸润的关系，并探讨亚低温的治疗作用。方法 采用大鼠大脑中动脉阻断（MCAO）模型，经免疫组化及HE染色，测定ICAM－1表达阳性微血管数及白细胞计数。结果 （1）脑缺血再灌注后，脑缺血坏死周边区的微血管内皮细胞表达ICAM－1及白细胞浸润增多，并于24h达到高峰，二者之间呈正相关（P＜0．01）；（2）缺血早期进行亚低温治疗能明显减轻缺血再灌注后ICAM－1的表达及减少白细胞浸润（P＜0．01）。结论 脑缺血再灌注后ICAM－1可介导白细胞和内皮细胞的粘附；亚低温干预治疗可减轻缺血再灌注后脑组织的损害。     

环磷酰胺对大鼠脑缺血再灌注后脑组织中ICAM-1、白细胞影响的研究

目的观察环磷酰胺对大鼠脑缺血再灌注后脑组织中ICAM-1表达、白细胞浸润的影响。方法36只雄性SD大鼠分为假手术组和脑缺血再灌注组。脑缺血再灌注组中包括环磷酰胺治疗组和生理盐水对照组,每组按脑缺血2h后再灌注2h、4h、6h、24h又分为4个亚组。脑缺血再灌注组于脑缺血2h再灌注后2h、4h、6h、24h处死动物,用免疫组织化学法观察再灌注后不同时间点脑组织中ICAM-1的表达,HE染色法观察白细胞的浸润程度。结果(1)脑缺血再灌注后,脑缺血坏死区周边ICAM-1的表达及白细胞的浸润增多,并于24h达高峰;环磷酰胺组在相同再灌注时间点的ICAM-1表达及白细胞的浸润均明显低于对照组。(2)ICAM-1的表达与白细胞的浸润呈现正相关性。结论脑缺血再灌注后,ICAM-1的表达上调,介导了白细胞和内皮细胞的粘附,参与了脑缺血再灌注损伤的过程。环磷酰胺治疗组ICAM-1的表达、白细胞的浸润均少于对照组,说明环磷酰胺有抑制粘附分子表达上调、抑制白细胞浸润的作用,因而具有神经保护的作用,为该治疗应用于临床提供了理论基础。     

大鼠脑缺血再灌注区ICAM-1表达与白细胞浸润的 观察及丹参的影响☆

】　目的　观察细胞间粘附分子(ICAM-1)蛋白在大鼠脑缺血再灌注的不同时程脑组织中的表达与中性白细胞浸润程度的关系及丹参对它们的影响。方法　SD大鼠分为3组假手术组、对照组及丹参组。大脑中动脉缺血2 h再灌注2 h、12 h、24 h、48 h、72 h、7 d、14 d后，分别进行ICAM-1免疫组织化学及组织HE染色。结果　在脑缺血再灌早期，脑微血管内皮细胞ICAM-1免疫反应开始逐渐增加，再灌注48 h达到高峰，再灌注14 d接近正常水平，同时脑缺血区中性白细胞浸润也随之增加，在时程上与ICAM-1表达同步。丹参组，再灌注48 h后，ICAM-1免疫阳性血管数及中性白细胞的浸润比同时间对照组明显降低。结论　脑缺血ICAM-1的表达与中性白细胞浸润密切相关，丹参能降低ICAM-1的表达，抑制中性白细胞的浸润。     

β-七叶皂甙钠对大鼠局灶性脑缺血再灌注后NF-κB、ICAM-1、VCAM-1表达的影响

目的探讨大鼠局灶性脑缺血再灌注脑组织缺血区不同时间点NF-кB、ICAM-1、VCAM-1蛋白表达的变化,及β-七叶皂甙钠干预效果。方法采用大鼠大脑中动脉闭塞法(MCAO)制作局灶性脑缺血再灌注模型,用免疫组织化学方法观察大鼠脑缺血再灌注不同时间段,NF-кB、ICAM-1、VCAM-1蛋白的表达。并在大鼠于脑缺血前24h、1h及再灌注即刻分别腹腔给予β-七叶皂甙钠5mg/kg,2h MCAO,再灌注24h、48h后取脑,运用TTC染色测算脑梗死体积,免疫组化染色检测NF-кB、ICAM-1、VCAM-1蛋白表达,分析β-七叶皂甙钠的干预效应。结果(1)脑缺血后缺血区脑组织NF-кB及ICAM-1、VCAM-1表达均增加,NF-kB于再灌注后12～24h表达达高峰,Ⅰ- CAM-1于再灌注后24h表达达高峰,VCAM-1于再灌注后24～48h表达达高峰。(2)NF-кB的表达与血管内皮I- CAM-1、VCAM-1的表达呈正相关。(3)β-七叶皂甙钠能显著降低脑缺血再灌注后24h和48h缺血区NF-кB、ICAM- 1及VCAM-1的表达增加。(4)β-七叶皂甙钠能明显减轻脑缺血再灌注后的脑组织损伤,再灌注24h脑梗死体积减少41.8%。结论(1)脑缺血再灌注后NF-кB、ICAM-1、VCAM-1大量表达,这可能是脑缺血再灌注损伤机制之一。(2)脑缺血后NF-кB的活化可能与微血管内皮细胞ICAM-1、VCAM-1蛋白表达调控有关。(3)β-七叶皂甙钠能够减轻脑缺血后的脑组织损伤,有神经保护作用。     

β-七叶皂甙钠对大鼠局灶性脑缺血再灌注后NF-κB、ICAM-1、VCAM-1表达的影响

目的 探讨大鼠局灶性脑缺血再灌注脑组织缺血区不同时间点NF-κB、ICAM-1、VCAM-1蛋白表达的变化,及β-七叶皂甙钠干预效果.方法 采用大鼠大脑中动脉闭塞法(MCAO)制作局灶性脑缺血再灌注模型,用免疫组织化学方法观察大鼠脑缺血再灌注不同时间段,NF-κB、ICAM-1、VCAM-1蛋白的表达.并在大鼠于脑缺血前24h、1h及再灌注即刻分别腹腔给予β-七叶皂甙钠5mg/kg,2h MCAO,再灌注24h、48h后取脑,运用TTC染色测算脑梗死体积,免疫组化染色检测NF-κB、ICAM-1、VCAM-1蛋白表达,分析β-七叶皂甙钠的干预效应.结果 (1)脑缺血后缺血区脑组织NF-κB及ICAM-1、VCAM-1表达均增加,NF-κB于再灌注后12～24h表达达高峰,ICAM-1于再灌注后24h表达达高峰,VCAM-1于再灌注后24～48h表达达高峰.(2)NF-κB的表达与血管内皮ICAM-1、VCAM-1的表达呈正相关.(3)β-七叶皂甙钠能显著降低脑缺血再灌注后24h和48h缺血区NF-κB、ICAM-1及VCAM-1的表达增加.(4)β-七叶皂甙钠能明显减轻脑缺血再灌注后的脑组织损伤,再灌注24h脑梗死体积减少41.8%.结论 (1)脑缺血再灌注后NF-κB、ICAM-1、VCAM-1大量表达,这可能是脑缺血再灌注损伤机制之一.(2)脑缺血后NF-κB的活化可能与微血管内皮细胞ICAM-1、VCAM-1蛋白表达调控有关.(3)β-七叶皂甙钠能够减轻脑缺血后的脑组织损伤,有神经保护作用.     

大鼠脑缺血再灌注模型粘附分子VCAM-1表达的研究

目的 探讨血管内皮细胞粘附分子（vascular cell molecule-1,VCAM-1)在脑缺血再灌注损伤中的作用和机制。方法 制作大脑中动脉梗死模型。分别于再灌注后6h,24h,36h,48h和7d5个时相点用免疫组化方法观察大鼠模型脑缺血区域VCAM-1的表达，并与永久性脑梗死，假手术组和正常大鼠组比较。结果 （1）正常对照组无VCAM-1的表达，假手术组在6h,24h,36h和48h均无VCAM-1的表达；（2）永久性脑梗死组6h后，在梗死周边区大脑微血管内皮细胞上和神经元上有VCAM-1的明显表达，24h表达达高峰，36-48h开始减弱，7d后完全消失；（3）缺血再灌注组6h后，在缺血周边区大脑神经元上和微血管内皮细胞上有较弱表达，24-48h达高峰，7d后在内皮细胞上仍有VCAM-1的持续表达。结论 缺血再灌注模型脑缺血区域有VCAM-1的表达，VCAM-1可能是缺血再灌注损伤的机制之一。     

局灶性脑缺血/再灌注损伤后大鼠脑组织tPA表达变化与细胞凋亡研究

目的　探讨大鼠脑缺血 /再灌注后脑组织内组织型纤溶酶原激活物 (t PA)表达变化及与细胞凋亡的关系和意义。方法　采用大鼠局灶性脑缺血 /再灌注模型 ,应用免疫组化染色及原位杂交技术检测脑组织 t PA表达变化 ,TU NEL 染色观察神经元的凋亡及其发生规律。结果　 t PA蛋白及 m RNA在缺血再灌注早期即开始表达 ,主要见于皮质损伤区周围及海马区 ,阳性着色的神经元表达明显 ,血管表达较弱。再灌注 4 8h神经元表达明显增强 ,缺血灶及其周边的微血管内皮表达也明显增强。再灌注 72 h表达有所下降。凋亡细胞主要出现于大脑皮质及尾壳核病变中心区的周围 ,再灌注 4 8～ 72 h达高峰。结论　脑缺血 /再灌注损伤可诱导神经元及血管内皮细胞 t PA表达增加 ,t PA可能通过促进细胞凋亡而介导再灌注损伤。     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.