三七三醇皂苷对脑缺血再灌注大鼠的保护作用

目的 通过对局灶性脑缺血大鼠不同再灌注时段的动态观察．探讨三七三醇皂苷(PTS)对大鼠局灶性脑缺血／再灌注动物模型的神经行为学和脑梗死体积的保护作用。方法 采用改良的线栓法制备大脑中动脉阻塞(MACO)2h、再灌注不同时间段(3h、6h、12h、24h、48h、72h、7d)的大鼠短暂局灶性脑缺血模型。动物随机分假手术组、生理盐水对照组、三七三醇皂苷(PTS)组。用Zea Longa5分制评分和TTC染色法评价神经行为学和脑梗死体积。结果 神经行为学评分除72h组有明显改善外．其余各组与生理盐水对照组比较无显著性差异。脑梗死体积除再灌注3h、6h外．其余各组与生理盐水组比较差异均有显著性意义。结论 三七三醇皂苷对大鼠局灶性脑缺血及再灌注损伤有一定的保护作用。     

川芎嗪注射液治疗大鼠脑缺血/再灌注损伤的时间窗

目的探讨川芎嗪注射液治疗局灶性脑缺血/再灌注损伤的时间窗。方法40只SD雄性大鼠,随机分为5组(n=8),对照组(即生理盐水组)和川芎嗪注射液治疗组(T1、T2、T4和T6组),分别于缺血/再灌注后1h、2h、4h和6h腹腔注射川芎嗪注射液(20mg/kg),每24h一次,共3次。采用右侧颈内动脉单丝尼龙线栓塞致大脑中动脉阻闭(MCAO)120min建立局灶性脑缺血模型。再灌注后72h,评估神经功能缺陷评分(NDS)并处死动物,取大脑行2,3,5-氯化三苯四唑(TTC)染色,以测量脑梗死容积。结果再灌注后72h测NDS,对照组明显高于T1组(P=0.001)、T2组(P=0.005)和T4组(P=0.002),T1、T2、T4和T6组间NDS无差异。再灌注后72h,对照组的脑梗死容积(205±72mm3)明显大于T1组(116±44mm3,P=0.001)、T2组(127±30mm3,P=0.003)和T4组(135±35mm3,P=0.007);在T1和T6组间也有统计学差异(P=0.035);其余各组的脑梗死容积无明显差异。结论川芎嗪治疗大鼠短暂局灶性脑缺血/再灌注损伤的有效治疗时间窗不宜超过4h。     

IGF-1对大鼠局灶性脑损伤c-fos表达的影响

目的研究胰岛素样生长因子-1(IGF-1)对大鼠局灶性脑缺血再灌注后c-fos表达的影响及与缺血时间关系,探讨IGF-1对脑缺血再灌注损伤的保护作用。方法制作SD大鼠大脑中动脉缺血再灌注模型。将55只SD雄性大鼠随机分为假手术组(n=5)、对照组(n=25)、IGF-1治疗组(n=25),其中后2组按缺血再灌时间(6h、12h、1d、3d、7d)不同可分为5个亚组,每组5只,治疗组于缺血2h再灌注1h后经腹腔注入40μg/kg稀释为1 ml的IGF-1,假手术组及对照组同时腹腔注入生理盐水1 ml。以上动物均在再灌注后规定时间点用4%多聚甲醛经心脏灌注固定,取大鼠脑组织,应用免疫组化S-P法和HE染色检测c-fos蛋白表达及脑组织结构病理变化。结果与对照组相比,治疗组大鼠脑组织c-fos表达明显减少,神经细胞坏死程度明显减轻。结论IGF-1在大鼠局灶性脑缺血再灌注损伤中起保护作用,其作用机制包括降低c-fos的表达,发挥神经保护作用。     

人尿激肽原酶对局灶性脑缺血再灌注大鼠VEGF表达影响的研究

目的 探讨人尿激肽原酶对局灶性脑缺血再灌注大鼠脑组织血管内皮生长因子(VEGF)表达的影响.方法 采用随机数字表法将56只雄性SD大鼠分为假手术组(8只)、生理盐水组(24只)、人尿激肽原酶组(24只),其中生理盐水组、人尿激肽原酶组依据再灌注后不同取材时间又分为6 h,12 h,24 h,72 h,7 d五个亚组.采用线拴法制备大鼠局灶性脑缺血再灌注模型,采用神经功能评分、TTC染色、脑梗死体积测定、光镜检测等方法对不同组大鼠予以评价.采用免疫组化技术观察缺血再灌注不同时间点大鼠脑组织梗死中心区及半影区VEGF表达变化情况.结果 人尿激肽原酶组大鼠神经功能评分低于生理盐水组大鼠(P<0.05);24 h脑梗死体积测定,人尿激肽原酶组平均值为(53 261.96±7 326.75)μm3,生理盐水组平均值为(92 715.84±13 755.44)μm3,差异有统计学意义(P<0.05);人尿激肽原酶组VEGF表达在不同时间点均明显强于生理盐水组(P<0.05).结论 人尿激肽原酶能减轻脑缺血再灌注模型大鼠的神经功能损伤程度,减少脑梗死体积,促进VEGF的表达,具有脑缺血后神经保护作用.     

经鼻给予VEGF治疗脑缺血/再灌注大鼠的量效关系

目的探讨经鼻给予血管内皮生长因子(VEGF)治疗脑缺血/再灌注损伤大鼠的量效关系。方法48只SD大鼠随机分为四组:低剂量组(100μg/mL)、中剂量组(200μg/mL)、高剂量组(500μg/mL)及盐水对照组(n=12)。通过阻塞大脑中动脉制作大鼠局灶性脑缺血90 m in再灌注损伤模型。缺血后1d、7d和14 d行神经功能评价,14 d动物被麻醉,行组织学检查,应用图像分析系统计算梗死体积、评价血管形成。结果与对照组相比,经鼻给予中剂量VEGF,可明显降低梗死体积,改善神经功能(P<0.01);而低和高剂量组对比于对照组,不能降低脑缺血后大鼠脑梗死体积和改善神经功能(P>0.05)。与对照组相比,经鼻给予中和高剂量VEGF,可增加缺血后脑表面血管形成(P<0.01);而低剂量组对比于对照组,不能促进脑缺血后血管生成(P>0.05)。结论经鼻给予中剂量VEGF可有效降低脑缺血/再灌注损伤大鼠梗死体积,改善神经功能,增加血管密度。因此经鼻给予中等剂量(200μg/mL)VEGF是治疗脑缺血/再灌注损伤的最佳剂量,其可用于进一步评价VEGF作用的有效实验剂量。     

门冬氨酸钾对局灶性脑缺血再灌注大鼠的保护作用研究

目的 观察门冬氨酸钾对大鼠局灶性脑缺血再灌注后神经细胞凋亡的保护作用。 方法 采用雄性SD大鼠右侧大脑中动脉闭塞模型,缺血2 h,再灌注22 h。大鼠随机分为5组,每组10 只,在缺血后1 h经腹腔注射给予生理盐水（1 ml/kg）或不同剂量门冬氨酸钾（10 mg/kg、25 mg/kg、 62.5 mg/kg和125 mg/kg）,观察不同剂量门冬氨酸钾对大鼠脑缺血再灌注后神经功能缺损和梗死 体积的影响。另取32只大鼠随机分为溶剂对照组和门冬氨酸钾组,在缺血后1 h腹腔注射生理盐水 （1 ml/kg）或门冬氨酸钾（62.5 mg/kg）,同时设立假手术组16只,检测三组大鼠脑组织三磷酸腺苷 （adenosine triphosphate,ATP）和乳酸水平（每组10只）,以及凋亡性细胞情况（每组6只）。 结果 与溶剂对照组比较,62.5 mg/kg剂量的门冬氨酸钾能显著改善神经功能缺损（P <0.001）, 降低梗死体积（P =0.011）;与溶剂对照组比较,25 mg/kg剂量的门冬氨酸钾能减少梗死体积 （P =0.040）,但神经功能评分无差异;10 mg/kg和125 mg/kg剂量的门冬氨酸钾组神经功能评分和 梗死体积与溶剂对照组均无差异。与溶剂对照组比较,门冬氨酸钾（62.5 mg/kg）能减少ATP的下降 （P =0.036）和细胞凋亡（P <0.001）。 结论 门冬氨酸钾对大鼠局灶性脑缺血再灌注后的细胞凋亡有保护作用。     

硫辛酸对大鼠脑缺血再灌注损伤的神经保护作用

目的研究硫辛酸对大鼠局灶性脑缺血再灌注损伤的保护作用,进一步探讨其机制。方法 54只雄性清洁SD大鼠按照随机原则平均分成3组:假手术组(18只)、脑缺血再灌注组(对照组18只)、脑缺血再灌注+硫辛酸治疗组(治疗组18只)。大鼠大脑中动脉局灶性缺血2 h(MCAO),再灌注24 h。治疗组在再灌注同时经颈外静脉给予硫辛酸20 mg/kg,假手术组和对照组给予相同体积的溶媒。采用TTC染色法检测大鼠脑组织梗死体积;采用RT-PCR法检测大鼠脑组织TNF-α的表达;采用TUNEL法检测大鼠脑组织凋亡细胞数。结果与假手术组相比,对照组和治疗组大鼠脑组织梗死体积,TNF-α的表达和凋亡细胞数均明显增加(均P0.05)。与对照组相比,治疗组大鼠脑组织梗死体积,TNF-α的表达以及凋亡细胞数均明显减少(均P0.05)。结论我们的研究结果表明,硫辛酸对大鼠脑缺血再灌注损伤具有保护作用,可能机制为减轻脑缺血再灌注引起的炎症反应和细胞凋亡。     

丹参酮ⅡA对大鼠脑缺血-再灌注损伤细胞间黏附分子-1表达及髓过氧化物酶活性的影响

目的 探讨丹参酮ⅡA对脑缺血-再灌注损伤大鼠的保护作用及其对细胞间黏附分子-1表达及髓过氧化物酶活性的影响.方法 80只Wistar大鼠随机分为假手术组、缺血-再灌注组(缺血组)、丹参酮ⅡA小剂量治疗组[小剂量组,15mg/(kg·d)]和丹参酮ⅡA大剂量治疗组[大剂量组,30mg/(kg·d)];线拴法建立局灶性脑缺血-再灌注大鼠模型,治疗组大鼠于手术前连续生理盐水灌胃后给予不同剂量的丹参酮ⅡA.免疫组织化学方法观察脑缺血-再灌注大鼠额顶叶皮质细胞间黏附分子-1表达水平、髓过氧化物酶活性、脑组织含水量及梗死灶体积.结果 脑缺血-再灌注后24 h,缺血组细胞间黏附分子-1表达阳性的血管数为(63.00±4.74)根/5个高倍视野,髓过氧化物酶活性为(0.42±0.04)U/g,与假手术组[0和(0.03±0.01)U/g]比较,差异有统计学意义(均P＜0.01);小剂量组细胞间黏附分子-1表达阳性的血管数为(41.20±4.55)根/5个高倍视野,髓过氧化物酶活性为(0.33±0.02)U/g,大剂量组分别为(26.40±3.78)根/5个高倍视野和(0.23±0.03)U/g,均低于缺血组(P＜0.01),两剂量组之间比较差异有统计学意义(P＜0.01).缺血组脑组织含水量为(92.13±2.62)%,梗死灶体积为(194.10±10.99)mm3,与假手术组[(81.09±1.47)%和0]比较差异有统计学意义(均P＜0.01);小剂量组脑组织含水量为(87.88±1.86)%,梗死灶体积为(140.86±5.25)mm3大剂量组分别为(83.36±2.90)%和(112.20±10.78)mm3,均低于缺血组(P＜0.01),两剂量组之间比较差异有统计学意义(P＜0.01).结论 丹参酮ⅡA对脑缺血-再灌注损伤具有保护作用,其机制可能与缺血-再灌注后细胞间黏附分子-1表达水平和中性粒细胞浸润受到抑制有关.     

免疫干预对大鼠缺血再灌注脑损伤的保护作用

目的:探讨免疫抑制剂甲基强的松龙对大鼠缺血再灌注脑损伤的保护作用。方法:采用改良的大鼠局灶性脑缺血再灌注损伤线栓模型,将缺血1h再灌注大鼠分为假手术组、生理盐水组、甲基强的松龙组,观察脑梗塞体积、血清胞浆酶及微血管内聚集与粘附的多形核白细胞(PMNL)的变化。结果:甲基强的松龙能够缩小脑梗塞的体积,使血清LDH、CK、CK-BB明显降低,并减少PMNL在微血管内聚集与粘附。结论:甲基强的松龙干预后能够减轻脑缺血再灌注损伤。     

莱菔硫烷对大鼠局灶性脑缺血再灌注损伤的保护作用及机制研究

目的 探讨莱菔硫烷对大鼠局灶性脑缺血再灌注损伤的保护作用及机制.方法 采用线栓法制备大鼠大脑中动脉阻断局灶性脑缺血模型,分别于MCAO后1h腹腔注射莱菔硫烷2.5mg/kg、5mg/kg、10mg/kg.于缺血2h再灌注24h时进行神经行为缺损评分,TTC染色评价脑梗死体积,测定脑组织中超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量.免疫荧光组织化学染色法检测黄核蛋白NQ01和脂质过氧化酶Prx6的表达.结果 莱菔硫烷给药组与对照组相比均能改善大鼠脑缺血再灌注后神经行为缺损评分,减少脑梗死体积.其中5mg/kg组能显著改善大鼠脑缺血再灌注后神经行为缺损评分,减少脑梗死体积,增强SOD活性,降低MDA含量.免疫荧光组织化学染色法提示NQ01和Prx6的表达明显增强.结论 莱菔硫烷对大鼠局灶性脑缺血再灌注损伤有神经保护作用,其机制可能与上调内源性抗氧化蛋白NQ01和Prx6的表达有关.     

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.     

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.