慢性应激对大鼠海马CA3区锥体细胞顶树突及血清皮质酮浓度的影响

目的探讨慢性应激对大鼠海马CA3区锥体细胞结构和血清皮质酮浓度的影响。方法将20只雄性Sprague-Dawley大鼠按体质量随机分为应激组和对照组,每组10只。采用高尔基染色法及酶联免疫分析方法,观察慢性强迫游泳应激对大鼠海马CA3区锥体细胞顶树突和血清皮质酮浓度的影响。结果应激组大鼠海马CA3区锥体细胞顶树突的总长度[(112±10)μm]短于对照组[(168±34)μm],差异有统计学意义(P<0.01);一级树突直径[(9.0±1.1)μm]大于对照组[(5.7±0.9)μm],差异有统计学意义(P<0.01);血清皮质酮浓度[(13±14)μg/L]低于对照组[(30±16)μg/L],差异有统计学意义(P<0.05)。结论慢性强迫游泳可引起大鼠海马CA3区锥体细胞顶树突及血清皮质酮浓度的改变。     

慢性冷水游泳应激对大鼠海马、前脑皮层神经颗粒素含量的影响

目的探讨慢性应激对大鼠海马和前脑皮层神经颗粒素(NG)含量的影响。方法将雄性SD大鼠随机分为应激组(予10℃冷水游泳应激,共2周)、装置对照组和正常对照组,每组10只。于应激前后测量三组大鼠的体质量变化情况,并记录每天应激过程中应激组和装置对照组的排便量以考察应激的强度,应激后以Westernblotting方法测定海马和前脑皮层中的NG含量(以NG含量与βActin含量的比值表示)。结果(1)应激前后,三组大鼠的体质量比较,差异均无统计学意义(P>0.05),但应激组的体质量增长相对缓慢;(2)应激第4—14天应激组的排便量多于装置对照组(P<0.01);(3)应激组和装置对照组海马的NG含量[分别为(0.66±0.13)和(0.94±0.26)]低于正常对照组[(1.93±0.53)],差异有统计学意义(P<0.01);(4)应激组前脑皮层的NG含量[(0.45±0.00)]低于装置对照组和正常对照组[分别为(2.76±1.74)和(2.87±1.63)],差异有统计学意义(P<0.01);(5)应激组海马NG含量高于前脑皮层(P<0.01);装置对照组海马NG含量低于前脑皮层(P<0.01);正常对照组海马与前脑皮层NG含量的差异无统计学意义。结论慢性应激导致海马和前脑皮层NG含量显著下降;对于时程长、程度严重、适应不良的冷水游泳应激,前脑皮层受损比海马更为严重;而对于时程长、程度微弱的装置应激,海马则比前脑皮层更为敏感。     

环磷酸腺苷反应元件结合蛋白在吗啡依赖及戒断大鼠脑区的表达

目的　研究吗啡依赖及吗啡戒断时环磷酸腺苷反应元件结合蛋白 (CREB)在大鼠脑内的表达。方法　将 1 5只雄性Sprague Dawley大鼠随机分为正常对照组、吗啡依赖组和吗啡戒断组 ,每组各 5只。于大鼠背部皮下注射吗啡 ,第 1天注射 2 0mg/kg ,逐日递增剂量 ,至第 5天达 1 0 0mg/kg ,形成大鼠吗啡依赖模型。吗啡戒断组大鼠在末次注射吗啡后 1 6h皮下注射纳洛酮 1mg/kg。采用免疫印迹法观察各组大鼠的前额叶皮质、伏隔核和海马等脑区CREB的表达。结果　 (1 )在前额叶皮质 ,吗啡依赖组和吗啡戒断组CREB的含量 (为相对光密度值 )分别为 [(1 31± 1 1 ) % ]和 [(1 33± 1 5) % ] ,均高于正常对照组 [(1 0 0± 1 4 ) % ] ,差异有显著性 (P <0 0 5) ;(2 )在伏隔核 ,三组CREB的差异无显著性(P >0 0 5) ;(3)在海马 ,吗啡戒断组CREB的含量 [(1 4 1± 1 8) % ]高于正常对照组 [(1 0 0± 1 4 ) % ] ,差异有非常显著性 (P <0 0 1 )。结论　大鼠处于吗啡依赖和戒断时CREB的表达在前额叶皮质和海马发生改变 ,表明多个脑区CREB表达的调节参与了阿片类物质依赖的形成     

应激对大鼠海马谷氨酸、天冬氨酸和γ-氨基丁酸含量的影响

目的　探讨应激对大鼠海马谷氨酸、天冬氨酸和γ 氨基丁酸 (GABA)含量的动态影响。方法　将 72只健康雄性大鼠随机分为 5个应激暴露不同时间组和对照组 ,每组 12只。利用高效液相色谱仪 紫外检测法 ,分别于应激第 1,3,7,14和 2 8天观察应激对大鼠海马谷氨酸、天冬氨酸及GABA含量的影响。结果　应激第 1天组大鼠海马谷氨酸和天冬氨酸含量与对照组相比 ,差异无显著性 ;但GABA含量 [(2 74 7± 0 339) μmol/g]低于对照组 [(3 719± 0 5 2 8) μmol/g;P <0 0 5 ]。应激第 3,7,14和 2 8天组谷氨酸含量 [分别为 (7 818± 0 799) μmol/g ,(9 0 0 7± 0 5 2 0 ) μmol/g,(8 0 4 9± 0 733) μmol/g和 (8 12 9± 1 5 5 6 ) μmol/g]高于对照组 [(6 4 11± 0 6 38) μmol/g];天冬氨酸含量 [分别为 (2 717± 0 2 5 8)μmol/g,(2 6 96± 0 317) μmol/g,(2 82 8± 0 4 6 8) μmol/g和 (4 6 4 9± 0 6 37) μmol/g]也高于对照组 [(2 0 0 3± 0 2 71) μmol/g];均P <0 0 1。应激第 14天组和 2 8天组GABA含量 [分别为 (4 4 6 2± 0 883) μmol/g和(4 4 97± 0 85 7) μmol/g]高于对照组 (P <0 0 5～0 .0 0 1) ,应激第 3天组和 7天组的GABA含量与对照组间的差异无显著性。结论　应激第 3天开始     

丹参多酚酸对慢性应激抑郁大鼠脑内细胞因子和糖皮质激素系统的影响北大核心CSCD

目的明确抑郁大鼠海马及前额叶皮质细胞因子和糖皮质激素系统的变化,探讨丹参多酚酸的干预作用及其机制。方法 38只雄性大鼠随机分为空白对照组(n=8)、应激对照组(n=7)、应激氟西汀组(n=8)、应激丹酚酸组(n=7)和应激联合组(n=8)等5组。除空白对照组外,其余4组采用慢性温和应激方法造模,持续6周,第4周起按照分组进行药物治疗,持续3周。第6周末时取大鼠前额叶皮质和海马,采用多因子检测方法检测细胞因子白介素1β(interleukin-1β,IL-1β)、白介素2(interleukin-2,IL-2)、干扰素γ(interferon-γ,IFN-γ)和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)及皮质酮水平,采用RT-PCR和western blot方法检测糖皮质激素受体(glucocorticoid receptor,GR)基因核受体亚家族3C组成员1 (nuclear receptor subfamily 3, group C,member 1,Nr3c1)和FK506结合蛋白(FK506 binding protein, Fkbp5)mRNA及其蛋白表达水平。结果应激对照组前额叶皮质IL-1β和TNF-α、海马IFN-γ和TNF-α及前额叶皮质和海马皮质酮水平高于空白对照组、应激氟西汀组、应激丹酚酸组和应激联合组(P<0.05)。所有大鼠前额叶皮质IL-1β与皮质酮水平呈正相关(r=0.34,P=0.04),海马TNF-α与皮质酮水平呈正相关(r=0.39,P=0.02)。应激对照组前额叶皮质Fkbp5 mRNA表达量较其他4组均升高(P<0.01),海马Fkbp5 mRNA、前额叶皮质和海马FKBP5蛋白、前额叶皮质和海马Nr3c1 mRNA及GR蛋白表达水平的组间差异均无统计学意义(P>0.05)。结论慢性应激大鼠前额叶皮质和海马促炎细胞因子和皮质酮水平、前额叶皮质Nr3c1和Fkbp5 mRNA表达水平增加,细胞因子与皮质酮水平呈正相关。丹参多酚酸和抗抑郁药物氟西汀可逆转这一变化。     

经颅磁刺激对脑梗死大鼠学习记忆与健侧海马锥体细胞树突和突触结构的影响

目的研究经颅磁刺激(TMS)对脑梗死后大鼠学习记忆功能,以及海马锥体细胞树突和突触结构的影响。方法将48只雄性SD大鼠随机分为正常组、模型组和TMS组,每组16只。采用线栓法对模型组和TMS组大鼠制作一侧大脑中动脉闭塞的脑梗死模型,并在制模后第2天,对TMS组给予每天2次、每次30个脉冲的TMS治疗,疗程4周;观察各组大鼠治疗后在Y-迷宫中的学习记忆成绩和梗死对侧海马锥体细胞树突和突触结构变化。结果(1)TMS组大鼠学习尝试次数[(18.4±4.8)次]少于模型组[(26.4±5.4)次;P<0.01],记忆再现次数[(6.1±1.3)次]多于模型组[(3.7±1.2)次;P<0.01];(2)TMS组海马CA3区锥体细胞树突顶树突总长度[(196±35)μm]长于模型组(175±33)μm;P<0.01]。(3)TMS组的突触后致密物质厚度[(68±11)nm]宽于模型组[(62±10)nm],穿孔性突触百分比(27.5%)高于模型组(10.0%),突触间隙[(16.7±1.8)nm]窄于模型组[(21.3±2.3)nm],均P<0.01和P<0.05。结论TMS能促进脑梗死大鼠学习记忆功能的恢复,其机制可能与海马锥体细胞树突和突触结构的改变有关。     

丹参多酚酸对慢性应激抑郁大鼠脑内细胞因子和糖皮质激素系统的影响

目的明确抑郁大鼠海马及前额叶皮质细胞因子和糖皮质激素系统的变化,探讨丹参多酚酸的干预作用及其机制。方法 38只雄性大鼠随机分为空白对照组(n=8)、应激对照组(n=7)、应激氟西汀组(n=8)、应激丹酚酸组(n=7)和应激联合组(n=8)等5组。除空白对照组外,其余4组采用慢性温和应激方法造模,持续6周,第4周起按照分组进行药物治疗,持续3周。第6周末时取大鼠前额叶皮质和海马,采用多因子检测方法检测细胞因子白介素1β(interleukin-1β,IL-1β)、白介素2(interleukin-2,IL-2)、干扰素γ(interferon-γ,IFN-γ)和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)及皮质酮水平,采用RT-PCR和western blot方法检测糖皮质激素受体(glucocorticoid receptor,GR)基因核受体亚家族3C组成员1 (nuclear receptor subfamily 3, group C,member 1,Nr3c1)和FK506结合蛋白(FK506 binding protein, Fkbp5)mRNA及其蛋白表达水平。结果应激对照组前额叶皮质IL-1β和TNF-α、海马IFN-γ和TNF-α及前额叶皮质和海马皮质酮水平高于空白对照组、应激氟西汀组、应激丹酚酸组和应激联合组(P0.05)。所有大鼠前额叶皮质IL-1β与皮质酮水平呈正相关(r=0.34,P=0.04),海马TNF-α与皮质酮水平呈正相关(r=0.39,P=0.02)。应激对照组前额叶皮质Fkbp5 mRNA表达量较其他4组均升高(P0.01),海马Fkbp5 mRNA、前额叶皮质和海马FKBP5蛋白、前额叶皮质和海马Nr3c1 mRNA及GR蛋白表达水平的组间差异均无统计学意义(P0.05)。结论慢性应激大鼠前额叶皮质和海马促炎细胞因子和皮质酮水平、前额叶皮质Nr3c1和Fkbp5 mRNA表达水平增加,细胞因子与皮质酮水平呈正相关。丹参多酚酸和抗抑郁药物氟西汀可逆转这一变化。     

苯妥英钠对应激鼠血清和海马NO含量的影响

目的　探讨慢性应激对大鼠血清和海马一氧化氮 (nitricoxide,NO)含量的影响及苯妥英钠对它们的效应。方法　利用强迫游泳作为应激源制作慢性应激模型 ,采用硝酸还原酶法测定各组大鼠血清和海马NO的含量。结果　对照组、应激组和应激给药组之间大鼠血清NO的含量差异无显著性 ;应激组大鼠海马NO的含量 (4 70± 15 9)nmol/g显著高于对照组 (2 34± 77)nmol/ g和应激给药组(2 0 2± 89)nmol/g (P <0 .0 1) ,后两组间的差异无显著性。结论　慢性应激对大鼠血清NO含量无影响 ,但可诱导大鼠海马NO含量升高 ,苯妥英钠可以抑制慢性应激所致海马NO的过度生成。     

慢性应激对大鼠海马CA3区长时程增强的影响

目的　探讨慢性应激对大鼠海马CA3区长时程增强 (LTP)的影响及机制。方法　将 34只Wistar大鼠随机分成应激组 (8只 )、应激 +盐水组 (8只 )、应激 +MK 80 1组 (8只 )及空白对照组 (1 0只 ) ,应激刺激为饮水冲突模型 ,分别于实验初和LTP检测前 1天评定大鼠情绪性行为 ,在应激 1 5天后检测大鼠强直性LTP ,测量强直后 1 ,5 ,1 0 ,30 ,60 ,90 ,1 2 0minLTP群体峰电位幅度及峰潜期。结果(1 )应激前各组情绪性行为评分的差异均无显著性 ;应激后 ,应激 +盐水组 [(4 33± 0 50 )分 ]、应激 +MK 80 1组 [(3 60± 0 55)分 ]及应激组 [(2 90± 0 74)分 ]的评分均高于对照组 [(2 0 2± 1 1 6)分 ] ,差异有显著性 (P =0 0 0 0 ) ;(2 )应激组测试刺激阈值较对照组高 (45V∶30V) ;(3)在强直后第 1 ,90min时的LTP群体峰电位变化率应激组 [分别为 (2 1 1± 58) %和 (2 4 3± 69) % ]、应激 +盐水组 [分别为 (1 69±92 ) %和 (1 82± 1 61 ) % ]低于对照组 [分别为 (30 2± 2 1 0 ) %和 (30 3± 1 4 1 ) % ]和应激 +MK 80 1组 [分别为(375± 99) %和 (489± 2 36) % ] ,差异有显著性 (P <0 0 5) ,应激 +MK 80 1组与对照组的差异无显著性 ;(4)各应激组于各时点LTP峰潜期均较对照组长 ,但差异未呈显著性。结论　慢性     

电针及氟西汀对抑郁大鼠行为学及海马神经元凋亡的影响

目的 探究电针及氟西汀对慢性应激抑郁大鼠行为学及海马神经元凋亡的影响.方法 65只Sprague-Dawley雄性大鼠,按随机数字表随机分为空白组、空白电针组、模型组、电针组、氟西汀组,每组13只.慢性应激后进行行为学评价;采用膜联蛋白V-异硫氰酸荧光素/碘化丙啶双染法检测海马神经元凋亡率;采用免疫组织化学方法检测海马bcl-2蛋白表达.结果 模型组大鼠旷场试验水平穿越格数[(1.6±1.3)格]、竖立次数[(0.4 ±0.2)次]、体质量增加量[(34±18)g]均明显低于空白组[分别为(51.1 ±22.3)格、(13.2±4.6)次、(128 ±21)g],P均＜0.05;海马神经元细胞凋亡率[(67±10)%]高于空白组[(53±13)%],P＜0.05;海马组织bcl-2蛋白阳性细胞计数[(28±10)个/mm<'2>]低于空白组[(78±22)个/mm<'2>],P＜0.05.电针组[分别为(39.3 ±14.3)格,(9.6 ±4.1)次,(81±43)g]、氟西汀组[分别为(37.2±15.1)格,(9.3±4.6)次,(80 ±35)g]上述指标均明显高于模型组(P＜0.05);海马神经元细胞凋亡率[电针组(30±9)%,氟西汀组(51±13)%]均低于模型组(P＜0.05);海马组织bcl-2蛋白阳性细胞计数[电针组(56±18)个/mm<'2>,氟西汀组(62±24)个/mm<'2>]均高于模型组(P＜0.05),而电针组与氟西汀组间的差异无统计学意义(P＞0.05).结论 电针和氟西汀可改善抑郁大鼠行为学症状,这种改善与海马细胞凋亡机制有一定相关性.     

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.     

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.     

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.     

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.     

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.