脑出血大鼠血肿周围白介素-10的表达及其与脑水肿的相关性

目的 探讨脑出血(ICH)大鼠血肿周围白介素-10(IL-10)的表达及其与脑水肿的相关性.方法 130只SD大鼠随机分为正常对照组、假手术组和ICH组;应用肝素化Ⅶ型胶原酶建立大鼠ICH模型;制模后12 h、24 h、48 h、72 h、7 d及14 d应用Bederson量表评定神经功能缺损程度,干/湿重法测定脑组织含水量,免疫组化方法检测脑组织血肿周围IL-10的表达.结果 (1)ICH组大鼠神经功能缺损评分与脑组织含水量均在ICH 12 h升高,48 h达高峰,7 d后恢复正常.(2)ICH组脑组织IL-10表达ICH 12 h明显升高,14 d达高峰,各时间点间均显著高于正常对照组和假手术组(P＜0.05～0.01).(3)ICH组神经功能缺损评分与脑组织含水量呈正相关(r=0.761,P＜0.01),脑组织IL-10表达与脑组织含水量、神经功能缺损评分呈负相关(r=-0.65,-0.753,均P＜0.01).结论 ICH大鼠血肿周围脑组织IL-10表达逐渐升高,可能参与了ICH后减轻脑水肿、促进神经功能恢复的脑保护作用.     

实验性脑出血后脑组织核因子-κB表达和含水量的变化及其相关性

目的 研究实验性脑出血(ICH)后血肿周围脑组织核因子-κB(NF-κB)表达和脑组织含水量的改变及其相关性.方法 采用自体不凝血注人大鼠尾状核制备ICH模型;用免疫组化法检测血肿周围脑组织NF-κB表达;用干湿重法测脑组织含水量.结果 与对照组相比,ICH 6h组血肿周围脑组织NF-κB表达开始明显增加,ICH 48h组达高峰,并持续到ICH 1周(P＜0.01～0.05);脑组织含水量ICH 12h组开始增多,24h组显著增高,72h组达高峰;NF-κB表达和脑组织含水量ICH 24h～1周组与假手术组之间差异有统计学意义(均P＜0.01);ICH后NF-κB阳性细胞数与脑组织含水量呈正相关(r=0.644,P＜0.01),NF-κB表达从开始到高峰均早于脑组织含水量的变化.结论 ICH后脑组织NF-κB表达增加,NF-κB可能通过炎性机制参与了ICH后继发脑水肿的形成.     

CVF干预对大鼠实验性脑出血后C9表达及脑水肿的影响

目的 研究大鼠实验性脑出血后血肿周围补体成分C9的表达情况及其与脑水肿的关系,探讨补体C9在脑出血后继发性损伤中的作用以及应用眼镜蛇毒因子（CVF）干预后的影响.方法 采用立体定向技术,将自体不凝血注入大鼠尾状核制备脑出血模型,将动物分为假手术组、出血组和CVF干预组,分别在不同时间断头取脑,连续切片作补体C9免疫组化染色和HE染色.结果 脑出血后2 h血肿周围脑组织开始表达C9,24 h达高峰;各组与假手术组之间比较有差异（P＜0.01）;血肿周围脑组织含水量在ICH后6 h开始增加（P＜0.05）,12 h明显增加,24～72 h达高峰（P＜0.01）,此后逐渐回落,2 w基本恢复正常水平.对侧半球相应部位及假手术对照组脑组织含水量没有明显变化;C9的表达脑组织含水量呈正相关关系（r=0.833,P＜0.05）;经CVF干预后,血肿周围组织C9表达量及脑组织含水量明显下降,干预组与出血组之间比较有显著差异（P＜0.01）.结论脑出血后补体级联激活,C9表达明显增加,脑组织含水量增加,经CVF干预后,C9表达下降,脑水肿减轻,能达到神经保护作用.     

实验性脑出血后脑组织核因子-κB表达和含水量的变化及其相关性

目的研究实验性脑出血（ICH）后血肿周围脑组织核因子-кB（NF-кB）表达和脑组织含水量的改变及其相关性。方法采用自体不凝血注入大鼠尾状核制备ICH模型;用免疫组化法检测血肿周围脑组织NF-кB表达;用干湿重法测脑组织含水量。结果与对照组相比,ICH6h组血肿周围脑组织NF-кB表达开始明显增加,ICH48h组达高峰,并持续到ICH1周（P〈0.01~0.05）;脑组织含水量ICH12h组开始增多,24h组显著增高,72h组达高峰;NF-кB表达和脑组织含水量ICH24h~1周组与假手术组之间差异有统计学意义（均P〈0.01）;ICH后NF-кB阳性细胞数与脑组织含水量呈正相关（r=0.644,P〈0.01）,NF-кB表达从开始到高峰均早于脑组织含水量的变化。结论ICH后脑组织NF-кB表达增加,NF-кB可能通过炎性机制参与了ICH后继发脑水肿的形成。     

红细胞致脑出血后血肿周围脑组织HO-1的表达

目的　观察红细胞致脑出血后血肿周围脑组织 HO- 1的表达、脑组织含水量的变化。方法　采用立体定向法将自体浓缩红细胞注入大鼠脑基底节区制作实验动物模型 ,通过免疫组化、干湿重法 ,观察血肿周围脑组织 HO- 1的表达及脑组织含水量。结果　血肿周围脑组织 HO- 1在 6 h即开始表达 ,2 4 h明显增多 ,2 4～ 4 8h达高峰 ,脑组织含水量在 2 4 h无明显变化 ,4 8h有所增加 ,72 h显著增加并达到高峰 ,随后逐步下降。二者成正相关 ( r=0 .773,P<0 .0 5 )。结论　 HO- 1的表达在红细胞致脑水肿的形成过程中起着重要的作用     

脑出血灶周HIF-1α的表达与脑水肿的实验研究

目的明确脑出血后灶周脑组织不同时间点HIF-1α蛋白的表达规律,在脑水肿的发生、发展过程中的可能作用,相关性及临床意义。方法本研究以不同时间点高血压脑出血患者开颅手术中取的脑出血灶周组织为病例组标本,按发病时间分为<6 h、6~24 h、24 h~3 d、>3 d组。以手术入颅路径上远离血肿处少许破坏的的脑组织做为对照组标本,通过干湿称重法测脑含水量,同时应用免疫组化染色方法,RT-PCR方法观察各组各时间点病灶周围脑组织HIF-1α的表达变化。结果 (1)脑组织水含量的变化,脑出血后脑水肿程度随出血时间的延长逐渐加重,在出血6 h内含水量即开始增高,24 h后较明显增高,3 d左右达到峰值,之后减轻(P<0.05)。(2)脑出血血肿灶周组织中HIF-1α圴有表达,对照组与出血组相比均有显著性意义(P<0.05),且出血组各时间点间比较均有差异(P<0.05)。出血6 h后免疫阳性细胞数开始增加,24 h~3 d组阳性细胞数最多,之后逐渐下降。HIF-1α与脑水肿成正相关。结论 (1)脑出血灶周HIF-1α的表达明显升高,与脑水肿密切相关。(2)HIF-1α的异常表达在高血压脑出血后脑水肿中起重要作用,促进脑水肿的发生,为脑出血的治疗提供新的靶点。     

大鼠实验性脑出血后血肿周围水通道蛋白-4动态变化的研究

目的研究大鼠脑出血后血肿周围水通道蛋白4(AQP4)的动态变化及其与脑水肿、脑损伤程度的关系。方法采用SD大鼠自体动脉血注入尾状核建立脑出血模型,应用免疫组织化学法、干湿重法、Alexis法分别检测大鼠脑出血后不同时间点血肿周围AQP4、脑组织含水量及神经功能缺损程度的动态变化。结果①血肿周围AQP4在脑出血后12h表达开始增强,1～3d达到高峰,7d后略高于正常,14d基本恢复正常。②脑组织含水量在出血后6h增加,1～3d达到峰值,7d明显减轻,14d基本恢复正常。③神经功能缺损从出血后6h开始,最重的时间点是12h～3d,7d明显减轻,14d基本恢复正常。④脑出血后血肿周围AQP4的表达与脑组织含水量之间存在关联(x2mh=16.49,P<0.05)。⑤脑出血后血肿周围AQP4的表达与神经功能缺损程度之间存在关联(x2mh=15.07,P<0.05)。结论①AQP4的表达与脑水肿、脑损伤的发生发展密切相关,是引起出血性脑水肿脑损伤的重要因素之一。②早期积极控制脑出血后AQP4的过度表达将是减轻和预防脑出血后脑水肿脑损伤的有效途径。     

实验性大鼠脑出血后TNF-α、ICAM-1的表达和脑水肿的研究

目的:探讨TNF-α、ICAM-1在大鼠脑出血后脑水肿中的表达及意义。方法:利用立体定向技术建立中等 量大鼠自体尾动脉血脑出血模型(50μl),于脑出血后6h、24h、48h、72h处死大鼠,进行脑含水量测定,并于脑出血后3h、 6h、12h、24h、48h、72h、7d处死大鼠,进行TNF-α、IGAM-1的免疫组化染色,并对结果进行统计处理。结果:大鼠脑出血 后脑水肿于48h达到高峰;大鼠脑组织表达TNF-α也于48h达到高峰,高于假手术组,分别为58．4±6．19和2±1．12,P <0．01;ICAM-1表达72h达高峰,与假手术组比较存在显著性差异,分别为7．8±0．84和0．8±0．84,P<0．01。结论: TNF-α、ICAM-1在大鼠脑出血后血肿周围表达的高峰与脑水肿高峰存在时间上的相关性,提示高表达的TNF-α、ICAM- 1可能参与了脑水肿形成。     

补体在脑出血后脑组织损伤机制中的作用

目的研究补体C9在大鼠实验性脑出血(ICH)后血肿周围组织中的表达情况,探讨补体C9在ICH后脑水肿中的作用以及应用眼镜蛇毒因子(CVF)干预后对血肿周围组织C9表达及脑组织含水量变化的影响。方法采用立体定向技术,将自体不凝血注入大鼠尾状核制备ICH模型,将动物分为假手术组、出血组和CVF干预组,分别在不同时间断头取脑,连续切片分别作补体C9免疫组化染色和HE染色,并进行脑组织含水量测定(干湿重法)。结果ICH后2h血肿周围脑组织开始表达C9,24h达高峰。血肿周围脑组织含水量在ICH后2h开始增加(P<0.05),6h明显增加,24～72h达高峰(P<0.01),此后逐渐回落,1周基本恢复正常水平,脑组织含水量与C9的表达呈正相关关系(r=0.938,P<0.01);对侧半球相应部位及假手术对照组脑组织含水量没有明显变化;经CVF干预后,血肿周围组织C9表达明显下降,干预组与出血组之间比较有显著差异(P<0.01)。CVF干预组脑组织含水量明显低于常规ICH组(P<0.01)。结论脑出血后补体级联激活C9表达明显增加,并证明通过CVF干预后,C9表达下降,脑水肿减轻,能达到神经保护作用。     

脑出血灶周组织ICAM-1与MMP-9表达的实验研究

目的研究大鼠实验性脑出血后血肿周围脑组织细胞间粘附分子-1（ICAM-1），基质金属蛋白酶-9（MMP-9）的表达。方法采用立体定向技术将自体不凝血注入大鼠尾状核区制备脑出血模型，免疫组化染色法检测血肿周围脑组织ICAM-1，MMP-9的表达。结果脑出血后6h血肿旁有少量ICAM-1表达阳性细胞，12h开始增多，3d达高峰；脑出血后6h血肿周围就有较多MMP-9表达阳性细胞，2d时阳性细胞最多；脑出血后ICAM-1与MMP-9的表达呈正相关（y=0．768，P〈0．05）。结论血肿周围组织ICAM-1、MMP-9表达上调提示两者可能参与了脑出血后继发性脑损伤。     

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.     

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.     

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.     

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.     

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.