大鼠急性颅脑损伤后早期脑微血管改变的形态学研究

报道大鼠实验性脑损伤后早期，１０分钟至２４小时，大脑皮层微血管减少，并有“微无血管区”，微血管内可见微血栓形成，血脑屏障通透性增加，出现脑水肿，提示微循环障碍缺血是产生外伤性脑水肿的重要病因因素，救治重型颅脑损伤要重视防治脑微循环障碍，纠正脑缺氧。     

外伤性脑水肿脑组织单胺递质变化的实验研究

在急性外伤性脑水肿模型上利用荧光分光法检测了脑损伤后１、２、４、８小时单胺递质、脑含水量及病理形态学的改变。结果表明：５－羟色胺（５－ＨＴ）、去甲肾上腺素（ＮＥ）和多巴胺（ＤＡ）在脑损伤后１、２小时无显著性改变，４小时均有显著性增高，８小时又降至正常水平。脑含水量在脑损伤后１小时有显著性增高（ｐ＜０．０１），损伤后８小时较４小时有显著性升高。病理形态学观察到脑外伤后血管源性脑水肿。并发现在血管源性脑水肿同时伴有细胞毒性脑水肿。实验结果提示ＮＥ、５－ＨＴ和ＤＡ通过引起脑组织毛细血管痉挛，脑血流量下降，使脑微循环发生障碍，加剧脑损伤的缺血、缺氧，使脑水肿进一步发展。     

AQP4在大鼠脑缺血再灌注损伤过程中作用机制

目的:探讨AQP4在大鼠脑缺血再灌注损伤过程中对脑损伤、脑水肿形成等的影响以及作用机制。方法:采用SD大鼠复制脑局限性缺血再灌注模型,应用免疫组织化学方法检测脑内AQP4蛋白,记录大鼠神经功能缺损程度、血脑屏障通透性、脑水肿程度的动态变化。结果:1.脑局限性缺血再灌注损伤后脑内AQP4蛋白水平迅速降低,至再灌注后12～24小时达最低水平,至再灌注7天时恢复到正常水平。2.脑水肿程度峰值出现在再灌注损伤第24～72小时、Evans蓝最大通透率出现在再灌注损伤第24～72小时。3.神经功能缺损最重的时间点出现在再灌注损伤的第24小时。4.分析再灌注24小时伤侧半球AQP4与同时间点的神经功能缺损评分的相关性,结果显示AQP4水平与神经功能缺损评分呈负相关性(R=-0.9767,P=0.023)。结论:1.脑缺血再灌注损伤过程中AQP4水平的迅速下降,是机体对脑损伤所作出的一种保护性反应,具有阻止血脑屏障破坏、减轻血管源性脑水肿和细胞源性脑水肿的效应。2.调节缺血后脑内AQP4的功能和表达水平可望成为新的治疗脑缺血再灌注损伤的靶点。     

腺苷A1受体激动剂CHA对缺血性脑水肿的影响

在沙土鼠脑半球缺血模型上，观察了腺苷Ａ１受体激动剂ＣＨＡ（Ｃｙｃｌｏｈｅｘｙｌａｄｅｎｏｓｉｎｅ）对缺血８ｈ内的卒中发生率、卒中症状、以及脑水肿的影响。分析了脑水肿程度与卒中症状的关系。结果显示：ＣＨＡ可以延迟沙土鼠缺血后卒中发生时间，降低卒中发生率，改善卒中症状，减轻缺血性脑水肿。卒中指数与脑组织比重呈明显的负相关。提示腺苷减轻脑水肿，可能是其抗缺血性脑损伤的保护作用之一。     

猫局部脑缺血:SPECT与病理

报告20只猫,在MCA闭塞7日内脑损伤的特点,SPECT呈像结果。计论了缺血程度、缺血持续时间与脑损伤的关系。提示在卒中的急性期,解除或缓解脑水肿是治疗缺血性脑损伤的关键。放射强度比值用来评价脑缺血程度具可信性。     

通心络对大鼠脑缺血-再灌模型脑保护作用的研究

目的探讨通心络胶囊对脑缺血再灌注损伤的保护作用机制。方法用Zea Longa方法制作大鼠大脑中动脉缺血-再灌模型,观察不同剂量的通心络对缺血-再灌脑损伤大鼠脑组织形态学、脑脊液、行为学等的影响。结果通心络不同剂量均能降低脑缺血-再灌损伤大鼠神经功能评分,减轻脑水肿、缩小脑梗死面积、降低脑脊液中兴奋性氨基酸及乳酸含量。结论通心络对脑缺血再灌注损伤有保护作用。     

大鼠弥漫性颅脑损伤后脑水肿和病理学变化

目的探讨大鼠弥漫性颅脑损伤后病理学变化规律及意义。方法成年健康SD雄性大鼠100只，以自由落体法建立大鼠弥漫性颅脑损伤模型，随机平均分为对照组及外伤后1h、3h、6h、12h、24h、48h、72h、7d和14d等10组．检测大鼠脑组织含水量并观察脑组织中炎症反应、毛细血管和神经元的结构变化。结果外伤后脑皮层组织含水量呈上升趋势．3h含水量有较大幅度升高，24h达高峰，其后下降，14d时仍处于较高水平，伤后6、12、24、48和72h组与对照组相比．脑组织含水量明显高于对照组（P〈0．05）。脑组织炎症反应、毛细血管和神经元结构变化与脑水肿变化相平行。结论弥漫性颅脑损伤后发生缺血、缺氧．导致微循环障碍，最终血-脑屏障结构破坏，神经细胞的代谢活动紊乱，使脑组织发生继发性脑损伤。弥漫性颅脑损伤后脑水肿是造成继发性脑损伤病理学变化的基础。     

实验性不同时间缺血性脑水肿病理观察

本组实验采用犬头颞部开窗、结扎脑底动脉,动态的观察了脑缺血6、12小时,1、2、3、4、5、7天后脑水肿病理变化过程和规律。实验观察证明,脑缺血性水肿过程可分为:脑缺血阶段,脑水肿、坏死阶段,脑损伤修复阶段。缺血12小时出现血管周围白细胞浸润。缺血2天脑水肿最为显著。缺血4天出现吞噬细胞。脑缺血后水肿其白质水肿比灰质更为明显。     

重型颅脑损伤后中枢性低钠血症的诊断与鉴别

重型颅脑损伤后中枢性低钠血症是临床常见的并发症，并且随脑水肿的发展而加重继发性脑损伤，而其临床表现往往被颅脑损伤掩盖，加上脱水剂的使用和限制液体的摄入等原因，容易漏诊、误诊。     

缺血性脑卒中与脑组织β—EP含量及脑比重的关系及丹参的影响

在沙土鼠脑缺血模型上，用放射免疫分析法测定了脑组织中的β－内啡肽（β－Ｅｎｄｏｒｐｈｉｎ，β－ＥＰ）的含量，观察了缺血后脑组织β－ＥＰ含量的变化及丹参对缺血后β－ＥＰ含量变化和卒中症候的影响。结果显示：沙土鼠缺血８ｈ后β－ＥＰ含量显著增加，且与卒中定候呈正相关，与脑比重呈负相关。丹参可以改善卒中症候，减轻脑水肿，抑制缺血后β－ＥＰ的升高．提示缺血后中枢β－ＥＰ的增加将会加重缺血性损伤，丹参对内源性阿片肽系统具有抑制作用，这可能是其抗缺血性脑损伤的机理之一。     

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.