去铁酮对大鼠脑出血后铁超载、活性氧含量及神经功能的影响

目的研究去铁酮(Dfp)对大鼠脑出血后铁超载情况下总铁含量、活性氧含量及神经功能缺损的影响。方法采用大鼠Ⅳ型胶原酶定位注射到大鼠右侧基底节区来制造脑出血模型,用原子吸收光谱法测定脑组织中的总铁含量,通过化学荧光法测定活性氧含量,并观察各组大鼠的神经功能缺损体征。结果 (1)脑出血(ICH)组及Dfp处理组各组较同期假手术(SH)组总铁含量显著增多,且ICH组以7 d最多(P<0.05);Dfp组与ICH组相比脑组织总铁含量显著减少(P<0.05)。(2)ICH组及Dfp组各组较同期SH组相比活性氧含量显著增多,以7 d最多(P<0.05);Dfp组与ICH组相比,活性氧含量各组之间没有统计学意义(P>0.05)。(3)ICH组和Dfp组各时间点神经功能评分均显著增高,以1 d~3 d最高,之后逐渐下降,差异无统计学意义(P>0.05)。结论数据显示大鼠脑出血后总铁含量显著增加,活性氧含量明显升高,并且有明显的神经功能缺损;Dfp可明显降低脑出血后脑组织中的总铁含量,但活性氧含量未发生明显变化,且不能改善神经功能缺损。     

去铁酮对大鼠脑出血后三价铁转运体及神经功能的影响

目的观察去铁酮(Dfp)对大鼠脑出血后铁超载情况下铁蛋白(Ft)、转铁蛋白(Tf)、转铁蛋白受体(TfR)及神经功能的影响。方法采用大鼠Ⅳ型胶原酶定位注射制造脑出血模型,应用免疫组化方法观察不同组别、时间段Ft、Tf、TfR的表达变化,同时观察神经功能评分。结果与假手术对照组相比,脑出血组Ft免疫阳性细胞数3 d、7 d、14 d显著增多,7 d最多;Tf免疫阳性细胞数各时间点均显著增高,以3 d、7 d最多;TfR免疫阳性细胞数1 d、3 d、7 d显著增多,以3 d、7 d最多;去铁酮干预组与脑出血组有相同变化趋势,但升高程度明显低于脑出血组;脑出血组、去铁酮干预组各时间点神经功能评分均显著增高,以1 d³ d最高,之后逐渐下降,差异无统计学意义。结论去铁酮可降低脑出血后Ft、Tf、TfR表达上调的程度,不能改善大鼠脑出血后神经功能障碍;脑出血后自身Ft、Tf、TfR的表达上调可能起神经保护作用。     

去铁胺干预对大鼠脑出血后水通道蛋白4 mRNA表达及脑水含量的影响

目的观察水通道蛋白4(AQP4)及脑水含量在脑出血模型组及去铁胺(DFO)模型干预组的动态变化。以期阐明AQP4及DFO在脑出血后水肿形成中的机制及作用。方法采用自体血脑出血模型,应用RT-PCR方法观察AQP4mRNA的表达,干湿重法测量血肿周围的脑水含量。结果 AQP4 mRNA表达在ICH各组及DFO干预3d、7d组较假手术组明显增高,且以第3天最高。DFO干预各组与同期ICH组相比AQP4mRNA表达显著降低, DF0干预第14天组AQP4 mRNA表达与对照组无差别。脑水含量显示在ICH第1、3、7天组及DFO干预3d组较假手术组明显增高,且以第3天最高;ICH 14d组及DF0干预第7天、第14天组均与正常组无差别;DFO干预第3天及第7天组较ICH组同期脑水含量显著减少。相关分析显示AQP4mRNA表达及脑水含量之间存在正相关关系。结论 AQP4在脑出血后水肿形成及消退中可能起重要作用,去铁胺可能为干预脑出血后水肿形成的有效手段。     

实验性脑出血后大鼠行为学和血肿周围组织病理学的研究

目的观察大鼠脑出血后不同时间点神经行为学和血肿周围脑组织病理学的特点。方法将成年SD大鼠随机分为假手术组和脑出血组;脑出血组大鼠通过立体定向术向脑内注入VII型胶原酶制成脑尾状核出血模型,并按不同时间点（1、3、7、14、28d）分为5个亚组。采用神经功能评分和HE染色分别观察脑出血大鼠神经行为学和脑组织形态学的改变。结果与假手术组相比,脑出血组大鼠的神经行为学评分3d时最明显[3d与1、7d无明显差异（P〉0.05）;与14d和28d有显著差异（P〈0.05）]。脑出血后1d在尾壳核区域可见血肿形成,呈椭圆形或不规则形;3d时脑水肿明显;7d时血肿周围脑组织有胶质细胞增生;14d时血肿区逐渐形成不规则囊腔;28d时囊腔仍然存在,出血周边区见胶质细胞进一步增多。结论脑出血后神经行为学的改变、血肿及囊腔的形成与出血时间有关。     

急性脑出血血肿体积动态变化研究

目的 研究急性脑出血血肿体积动态变化.方法 对30例急性期脑出血患者分别于起病6h以内、1d、3d、7d、14d进行头颅CT扫描,采用体视学法对脑出血血肿及周围低密度水肿灶进行测量,计算二者比值,并根据出血量将患者分为少量及中等量出血组,比较2组血肿、水肿体积及CSS评分. 结果 脑出血急性期血肿体积逐渐缩小,周围低密度水肿灶体积逐渐扩大,7～14d达高峰,差异有统计学意义(P＜0.05),血肿体积与周围低密度水肿灶体积有相关性(|r|=0.75),2组的血肿/水肿比值差异无统计学意义(P＞0.05),2组的CSS评分差异有统计学意义(P＜0.05),但2组的水肿体积与CSS评分无相关性.结论 急性脑出血后起病至3d血肿体积无明显变化,水肿体积小,3～7d后血肿开始逐渐缩小,而水肿明显扩大,14d达高峰.少量及中等量出血血肿及水肿体积变化规律相同,血肿量直接影响CSS评分,而与水肿量无明显相关性.     

脑出血微创术后鞘内注射地塞米松疗效观察

目的评估脑出血微创血肿引流术后鞘内注射地塞米松对脑出血患者颅内血肿周围水肿的疗效。方法 162例经微创血肿引流术治疗的脑出血患者随机被分为观察组(81例)和对照组(81例)。观察组微创术后给予血肿腔内注射地塞米松,每日2 mg,连用5 d;对照组鞘内未注射地塞米松外,其治疗方法等均与观察组保持一致,以2组血肿周围水肿大小和神经功能缺损作为评分标准。结果观察组微创术后7 d和14 d血肿周围水肿大小较对照组明显减小,差异有统计学意义(P0.05或P0.01);观察组术后7 d和14 d神经功能缺损评分与对照组比较明显改善,差异有统计学意义(P0.05或P0.01)。2组在治疗过程中未见相关的药物不良反应。结论脑出血微创术后鞘内注射地塞米松可明显减轻脑血肿周围水肿,并能促进脑出血患者的神经功能恢复。     

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。     

脑出血急性期合并高血压患者血压与血肿、水肿的相关性研究

目的研究脑出血急性期合并高血压患者血压与血肿、水肿的相关性。方法选取我院接诊的30例脑出血急性期合并高血压患者为研究对象。调查分析30例患者脑出血后1d、3d、5d、7d血压、血肿体积以及血肿周围水肿体积,进而计算出1~3d、3~5d及5~7d的血压变化率、血肿变化率以及血肿周围水肿变化率。结果患者脑出血后,随着出血时间的增加,收缩压、舒张压以及平均血压均持续升高,但血肿体积及血肿周围水肿体积并未随着脑出血时间的增加而持续增加。患者收缩压变化率与血肿变化率呈正相关(r=0.764 1,P=0.0000),收缩压变化率与血肿周围水肿变化率呈正相关(r=0.518 2,P=0.025 3),平均血压变化率与血肿变化率以及血肿周围水肿变化率无相关性,舒张压变化率与血肿变化率以及血肿周围水肿变化率无相关性。结论脑出血急性期合并高血压患者脑出血后血压显著升高,收缩压波动可能促使血肿以及血肿周围水肿扩大。     

静脉泵控尼莫地平治疗高血压脑出血临床研究

目的探讨早期应用尼莫地平治疗急性高血压脑出血及控制继发性再出血的临床疗效,分析可能机制。方法将符合入组标准的82例急性高血压脑出血患者随机分为2组,实验组42例,应用尼莫地平注射液微量泵静脉泵入,共7d;对照组40例,应用20%甘露醇注射液静滴,2组其余基础治疗均相同。2组均在入院时、入院后1、3、7、21d行头颅CT检查,测量血肿体积、血肿周围水肿带体积,并给予神经功能缺损评分,入院时及28d后行生活自理能力量表评分,并进行比较。结果2组在血肿体积、血肿周围水肿带体积、神经功能缺失评分、生活自理能力量表评分等方面差异均有统计学意义(P均0.05),实验组疗效显著优于对照组。结论脑出血急性期给予尼莫地平降压止血治疗,不仅可以降低血肿扩大及再出血的发生风险,减轻血肿周围水肿带,且可以降低致残率,改善临床转归。     

大鼠脑出血模型中神经细胞凋亡与自由基水平的相关性

目的 研究脑出血后血肿周围组织不同自由基水平对于细胞凋亡的影响.方法 成年SD大鼠随机分为4组:假手术组、模型组、1mg/kg依达拉奉组、3 mg/kg依达拉奉组,各组又根据造模后处死动物的不同时间(6 h,12 h,24 h,48 h,72 h,7 d,14 d)分为七个亚组,假手术组中每个亚组1只大鼠,其余三组中每个亚组6只大鼠.左尾壳核立体定向注入自体血80 μL,制作大鼠脑出血动物模型.分光光度计法检测血肿周围丙二醛(mflonaldehyde,MDA)及羟自由基含量,末端转移酶标记技术(terminal deoxynucleotidyltransfemse-mediated dUTP-biotin nick end labeling,TLINEL)检测血肿组织周围细胞凋亡数,并分析血肿周围组织自由基水平和凋亡相关性.结果 (1)模型组羟自由基及MDA含量较假手术组明显增加,四组间进行统计学分析,具有显著性差异.(2)模型组和两种剂量的依达拉奉组均于6 h即可观察到TUNEL阳性细胞,24 h明显增加,72 h时达到高峰,7 d时明显减少,14 d时于血肿周边仍可见少量阳性细胞.(3)凋亡细胞数与脑组织产生自由基能力(r=0.2003)及MDA含量(r=0.6563)具有相关性.结论 脑出血后细胞凋亡数和自由基水平变化趋势相同,二者具有相关性,提示自由基可能参与诱导出血后神经元及胶质细胞凋亡.     

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.