硼中子俘获疗法诱导U87胶质瘤细胞凋亡

目的 探讨硼中子俘获疗法(BNCT)对人脑胶质瘤细胞株U87的增殖抑制和诱导凋亡的作用及可能机制.方法 实验分为未照射组(0 Gy)、γ射线对照组(4、8 Gy)、反应堆组(3.5 Gy)、BNCT组(4、8 Gy).采用形态观察、流式细胞仪Annexin V/PI荧光染色、四甲基偶氮唑蓝(MTT)法等方法观察BNCT对U87细胞的增殖抑制和诱导凋亡的作用,以免疫组织化学技术检测P53蛋白的表达,应用western blot检测BCL-2、BAX蛋白表达的变化.结果 硼中子照射后细胞出现典型的凋亡形态改变.BNCT 4、8 Gy组处理后48 h细胞的凋亡率分别为65.1%、85.9%.BNCT 4、8 Gy组细胞生长抑制作用显著高于同等剂量的γ射线照射组(P＜0.01).未照射的U87细胞P53蛋白表达阴性,BNCT4、8 Gy照射后P53蛋白表达阳性.BNCT4、8 Gy照射后BCL-2蛋白表达下降,BAX蛋白上升.结论 BNCT对U87细胞具有显著的增殖抑制作用,并有剂量、时间依赖性特点.     

肿瘤RNA冲击致敏树突状细胞治疗G422胶质母细胞瘤的实验研究

目的 研究G422肿瘤细胞RNA体外冲击致敏的树突状细胞（DC）回输诱导体内产生保护性免疫反应及对颅内荷瘤小鼠的免疫治疗效应，探讨以DC为基础的疫苗对脑胶质瘤治疗的可行性。方法 提取G422胶质母细胞瘤RNA冲击致敏DC制成疫苗，分别进行免疫保护和免疫治疗的体内实验，以及细胞毒性T淋巴（CTL）体外诱导及活性检测，并与PBS，未经致敏的DC，G422肿瘤细胞RNA组进行对照。结果 疫苗能诱导产生针对G422肿瘤抗原特异性CTL，具有非常显著性差异（P＜0．01），接种疫苗后的小鼠能抵抗G422的再次攻击（P＜0．01），疫苗组生存期较对照组延长（P＜0．05）。结论 肿瘤RNA体外冲击致敏DC，然后将之回输免疫接种至颅内荷瘤小鼠能显著地诱导机体产生抗原特异性CTL，激活抗肿瘤T细胞，具有免疫保护和免疫治疗作用，为DC疫苗免疫治疗胶质瘤提供了实验基础及理论依据。     

内皮抑素基因在其治疗的G422小鼠胶质母细胞瘤中的表达

目的观察内皮抑素（End）在携带小鼠内皮抑素基因的腺病毒（Ad-mEnd）治疗的G422荷瘤小鼠瘤体内的表达。方法用昆明种G422皮下荷瘤小鼠24只，在成瘤直径约3mm时分为空病毒保存液组、携带绿色荧光蛋白基因的腺病毒（Ad-GFP）组、Ad-mEnd单剂量组和Ad-mEnd重复给药组。各组小鼠瘤体内各注入相应试剂。用RT-PCR和western blot等方法测定End在肿瘤内的表达。结果Ad-mEnd单剂量组和重复给药组的mRNA值分别为2．73和5．14；重复给药组持续高水平表达，而单剂量组只能维持2周。结论End在Ad-mEnd治疗的小鼠G442瘤体内有良好表达，多次治疗可维持End的表达量。     

^60Co头部照射与卡氮介合用双脑荷G422瘤小鼠的治疗作用及对免疫功能的影响

本实验观察了头关照射与卡氮介（BCNU）合用对脑荷G422瘤小鼠的治疗作用，结果表明：二者合用不仅能显著延长荷瘤鼠的平均生存期，同时还可部分减轻BCNU的对荷瘤鼠脾脏T、B淋巴细胞增殖的抑制。     

硼中子俘获疗法诱导U251胶质瘤细胞凋亡

目的研究硼中子俘获疗法（BNCT）能否诱导体外培养的U251细胞发生凋亡，并探讨其诱导细胞凋亡的机制。方法采用四甲基偶氮唑蓝（MTT）法绘制细胞生长曲线，应用光镜、荧光显微镜、透射电子显微镜观察BNCT后细胞形态改变；使用流式细胞仪检测细胞凋亡率；利用细胞克隆形成实验分析细胞存活分数；用免疫组织化学方法检测相关蛋白表达的变化。结果在体外试验中BNCT对U251细胞的杀伤力强，并观察到了典型的细胞凋亡改变，4、8Gy照射后48h流式细胞仪检测，细胞凋亡率分别为60．2％、80．6％。在凋亡过程中，p53蛋白表达明显增高，而bcl-2蛋白表达下调。结论BNCT可诱导U251细胞发生凋亡，其机制可能与p53基因表达上调及bcl-2基因表达下调有关。     

贝伐珠单抗联合高压氧治疗小鼠胶质母细胞瘤的效果

目的 探讨贝伐珠单抗（Bev）联合高压氧（HBO）对小鼠胶质母细胞瘤（GBM）的治疗作用。方法 体外培养U251细胞,随机分为对照组、Bev组（Bev作用24 h）、HBO组（HBO治疗1次）和Bev+HBO组（Bev作用24 h后,接受HBO治疗1次）,采用MTT法检测细胞增殖能力,采用划痕实验和Transwell小室实验检测细胞迁移和侵袭能力。取100只雄性BALB/c裸鼠,右侧纹状体注射U251细胞建立GBM模型,造模后7 d随机分为对照组（腹腔注射PBS,3次/周,连续2周）、Bev组（腹腔注射Bev,5 mg/kg,3次/周,连续2周）、HBO组（HBO治疗,1次/d,连续2周）、Bev+HBO组（同时接受Bev和HBO处理2周）;每组取10只小鼠记录生存时间;每组取5只小鼠,HE染色测定肿瘤体积;每组取5只小鼠,CD34免疫组化染色测定肿瘤组织微血管密度（MVD）;每组取5只小鼠,PCR检测肿瘤组织基质金属蛋白酶（MMP）9 mRNA表达水平。结果 Bev对U251细胞增殖能力无明显影响（P>0.05）,明显增强U251细胞迁移和侵袭能力（P<0.01）;明显降低肿瘤组织MVD（P<0.05）,明显增加肿瘤组织MMP9 mRNA表达水平（P<0.05）,但对荷瘤小鼠肿瘤体积及生存时间无明显影响（P>0.05）。HBO明显抑制U251细胞增殖、迁移、侵袭能力（P<0.01 ）,明显降低荷瘤小鼠肿瘤组织MMP9 mRNA表达水平（P<0.01）,但对荷瘤小鼠生存时间、肿瘤体积及肿瘤组织MVD均无明显影响（P>0.05）。Bev联合HBO明显抑制U251细胞增殖、侵袭和迁移能力,明显降低荷瘤小鼠肿瘤组织MVD和MMP9 mRNA水平（P<0.05）,明显缩小肿瘤体积（P<0.05）,明显延长荷瘤小鼠的生存时间（P<0.01）。结论 单独应用Bev或HBO对GBM小鼠肿瘤体积及生存时间无明显影响,但Bev联合HBO明显抑制小鼠GBM生长,明显延长小鼠生存时间。     

少突胶质细胞瘤的诊断和分子标记物研究进展

少突胶质细胞瘤是起源于少突胶质细胞的肿瘤，2007年WHO最新分级将少突胶质细胞瘤分为低级别少突胶质细胞瘤（Ⅱ级）、高级别少突胶质细胞瘤（Ⅲ级）和多形性恶性胶质瘤（Ⅳ级）。在由胶质细胞分化的肿瘤中，其发生率排在第三位，占颅内原发肿瘤的4．2％，胶质细胞瘤的5％～20％。少突胶质细胞瘤多见于成人，其中40～60岁为发病高峰期，约有55％的病例出现在这一时期。     

树突状细胞疫苗治疗G422胶质母细胞瘤的实验研究

目的研究G422肿瘤细胞RNA体外冲击致敏的树突状细胞(DC)回输诱导体内产生保护性免疫反应及对颅内荷瘤小鼠的免疫治疗效应,探讨以树突状细胞为基础的疫苗对脑胶质瘤治疗的可行性.方法提取G422胶质母细胞瘤RNA或肿瘤提取物冲击致敏DC制成疫苗,分别进行免疫保护和免疫治疗的体内实验,以及细胞毒性T淋巴细胞(CTL)体外诱导及活性检测,并与PBS、未经致敏的DC、G422肿瘤细胞RNA组进行对照.疫苗能诱导产生针对G422肿瘤抗原特异性CTL,差异具有非常显著性(P＜0.01),接种疫苗后的小鼠能抵抗G422的再次攻击(P＜0.01),荷瘤小鼠接种疫苗后生存期较对照组延长(P＜0.05).结果疫苗能诱导产生针对G422肿瘤抗原特异性CTL,差异具有非常显著性(P＜0.01),接种疫苗后的小鼠能抵抗G422的再次攻击(P＜0.01),荷瘤小鼠接种疫苗后生存期较对照组延长(P＜0.05).结论肿瘤RNA或肿瘤提取物冲击致敏DC能诱导小鼠产生抗原特异性CTL,激活抗肿瘤T细胞,具有免疫保护和免疫治疗作用.该实验为DC疫苗免疫治疗胶质瘤提供了实验基础.     

猪苓多糖对脐血造血干细胞体外扩增及干细胞移植后免疫重建的调节效应★

目的：人脐血造血干细胞得以移植于小鼠体内，其理论基础是放射线照射使小鼠骨髓枯竭，龛位腾出，为移植的脐血造血干细胞提供空间，而猪苓多糖是从中药猪苓中提取的多糖成分，具有免疫调节抗肿瘤作用，也是一种非T细胞促有丝分裂素，对放射线照射有一定的防护作用。观察猪苓多糖对脐血造血干细胞体外扩增及干细胞移植后免疫重建效应。 方法： 实验于2004-06/2006-05在兰州大学基础医学院免疫研究所完成。①实验材料：清洁级BALB/c小鼠由兰州生物制品研究所提供，8周龄，体质量约20 g，雌雄各半，实验过程中对动物处置符合动物伦理学标准。脐血样本由兰泰医院妇产科提供，产妇及家属对实验知情同意，并经医院伦理委员会批准。猪苓多糖由兰州大学第一医院提供。②实验方法：应用20，17.5，12.5，7.5 mg/L猪苓多糖体外扩增培养脐血造血干细胞，并测定细胞增殖率及CD34+细胞数。将BALB/c小鼠分为正常对照组：尾静脉、腹腔注射等量生理盐水；照射空白组：3.5Gy经60Coγ放射线照射联合尾静脉、腹腔注射等量生理盐水；照射药物组：3.5Gy经60Coγ放射线照射联合尾静脉注射等量生理盐水、腹腔注射猪苓多糖；照射移植组（n =15）：3.5Gy经60Coγ放射线照射联合脐血造血干细胞移植、腹腔注射等量生理盐水；照射移植药物组：3.5Gy经60Coγ放射线照射联合脐血造血干细胞移植、腹腔注射猪苓多糖。③实验评估：观察小鼠生存状况及血常规变化，流式细胞仪测定CD3、CD4、CD8、CD19水平。 结果：57只小鼠均进入结果分析。①12.5 mg/L猪苓多糖增殖效率最为显著（P < 0.01），流式细胞仪测定显示CD34+细胞数扩增了6.33倍。移植药物组小鼠死亡率最低，死亡高峰集中在照射移植后7~14 d左右。②移植药物组小鼠血象恢复正常，并且时间明显短于其他实验组（P < 0.05）。③细胞及体液免疫恢复情况，移植药物组小鼠各项指标水平与正常小鼠无差别（P > 0.05），与其他各组小鼠比较，除CD4、CD19水平与照射移植小鼠无差别外均有差别（P < 0.05）。 结论：猪苓多糖对脐血造血干细胞有明显扩增作用，并能促进脐血造血干细胞移植小鼠免疫造血重建。     

Olig-2在人脑胶质细胞瘤中的表达及临床意义

目的研究少突胶质细胞转录因子-2（Olig-2）在人脑胶质细胞瘤组织中的表达,并探讨其临床意义。方法采用免疫组化sP法和蛋门印迹技术（Westernblot）,检测96例脑胶质细胞瘤患者的手术标本,WHO分类：Ⅰ级26例,Ⅱ级28例,Ⅲ级20例,Ⅳ级22例;组织学分类：巨细胞星形胶质细胞瘤26例,少突胶质细胞瘤28例,间变性星形胶质细胞瘤20例,多形胶质母细胞瘤10例,髓母细胞瘤12例和10例颅脑损伤内减压脑组织标本中Olig-2蛋白的表达水平：结果免疫组化结果表明：巨细胞星形胶质细胞瘤阳性表达牢为23．08％（6／26）,少突胶质细胞瘤阳性表达率为82．14％（23／28）,间变性星形胶质细胞瘤阳性表达率为40．00％（8／20）,多形胶质母细胞瘤阳性表达率为30．00％（3／10）,髓母细胞瘤阳性表达率为75．00％（9／12）和正常脑组织阳性表达率为60．00％（6／10）;Olig-2阳性率在良性（Ⅰ＋Ⅱ）和恶性（Ⅲ＋Ⅳ）中分别为53．70％（29／54）和47．62％（20／42）,统计学处理无明显差异（P〉0．05）;少突胶质细胞瘤Olig-2阳性率82．14％（23／28）和其它病理类型肿瘤阳性率38．24％（26／68）比较有明显差异（P〈0．05）;Westernblot结果显示少突胶质细胞瘤中Olig-2蛋白的表达明显高于其它类型胶质细胞瘤及正常脑组织（P〈0．05）。结论Olig-2在少突胶质细胞瘤中明显高表达,但表达水平与脑胶质细胞瘤恶性程度无明显相关,Olig-2可以作为人脑少突胶质细胞瘤与其它类型胶质细胞瘤鉴别诊断的重要标记物.     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

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.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

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.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.