依达拉奉对癫痫大鼠脑内谷氨酸的影响

目的 探讨依达拉奉对戊四氮致痫大鼠脑中谷氨酸的影响.方法 30只成年SD大鼠随机分为对照组、癫痫组和治疗组,癫痫组和治疗组大鼠腹腔注射戊四氮60mg/kg,诱导癫痫发作.治疗组于注射戊四氮之前1h经腹腔注射依达拉奉30mg,并观察1h.然后处死大鼠取脑,应用柱前衍生HPLC-荧光法测定大鼠脑皮质谷氨酸(Glu)的含量.结果 治疗组痫性发作潜伏期、平均痫性发作等级及脑内谷氨酸含量与癫痫组相比差异均有显著性(P<0.01).结论 依达拉奉可以通过拮抗氧自由基并抑制谷氨酸的释放,在癫痫发作中发挥保护作用.     

新生期大鼠惊厥发作后血清神经元特异性烯醇酶、S100蛋白的动态变化及其意义

目的探讨新生期大鼠惊厥发作后血清神经元特异性烯醇酶(NSE)、S100蛋白(S100B)的动态变化及其意义。方法 80只新生期SD大鼠随机分为单次对照组(8只)、反复对照组(8只)和单次惊厥组(32只)、反复惊厥组(32只)。新生大鼠惊厥模型采用三氟乙醚诱导法建立。采用ELISA法测定各组大鼠血清NSE、S100B水平。结果单次惊厥组新生期大鼠致痫后12 h、24 h时血清NSE水平均明显高于单次对照组(P0.05~0.01)。反复惊厥组新生期大鼠致痫后12 h、24 h、48 h血清NSE水平均明显高于反复对照组(P0.05~0.01)。单次惊厥组新生期大鼠致痫后24 h时血清S100B明显高于单次对照组(P0.01)。反复惊厥组新生期大鼠致痫后12 h、24 h、48 h时血清S100B水平均明显高于反复对照组(P0.05~0.01)。结论NSE、S100B是新生期惊厥性脑损伤敏感生化指标,反复惊厥更易造成脑损伤。     

癫痫持续状态大鼠脑损害及血清烯醇化酶的变化及意义

目的观察大鼠致痫后血清烯醇化酶(neuron specifi cenolose,NSE)水平变化及海马组织病理学改变。方法采用氯化锂-匹罗卡品联合腹腔注射制成大鼠癫痫持续状态模型(status epileptitus,SE)。用放射免疫法分别对对照组、地西泮干预组、实验组SE后不同时间点血清中NSE水平及常规病理变化进行观测。结果血清NSE水平在大鼠SE后6h开始升高,24~48h达高峰,72h开始下降,1周后趋于正常;实验组血清NSE水平的动态变化与对照组和干预组比较有统计学意义(P<0.05),而且常规病理也可见海马区神经元变性、坏死性改变,以CA1、CA3区及颞叶皮层为重。而对照组和地西泮干预组之间血清NSE水平比较无统计学意义(P>0.05),也无病理形态学变化。结论大鼠SE后可引起脑组织损害,以CA1、CA3区及颞叶皮层损害为主。血清NSE水平是反映神经元损伤的客观生化指标。     

颅脑损伤患者血清与脑脊液IL-1β及NSE水平的变化及临床意义

目的探讨颅脑损伤患者血清与脑脊液IL-1β及NSE水平的变化及临床意义。方法选取2014-06—2016-01我院收治的96例颅脑损伤患者为研究对象(实验组),选取同期门诊健康者30例为对照组,应用双抗体夹心酶联免疫吸附试验法(ELISA)检测样本IL-1β及NSE的含量,比较实验组发病入院后不同时间点与对照组血清与脑脊液IL-1β及NSE的水平。依据患者入院时的格拉斯哥昏迷量表(GCS)评分将其分为轻度组(n=36)、中度组(n=32)和重度组(n=28),对比各组患者血清与脑脊液IL-1β及NSE水平的变化。结果观察组血清及脑脊液IL-1β及NSE水平均明显高于对照组(P0.05);发病入院1d、3d,颅脑损伤患者血清及脑脊液IL-1β及NSE水平均呈升高趋势(P0.05),且在发病后第3天达到高峰;发病入院后第7天,血清及脑脊液IL-1β及NSE水平均轻微下降。轻度、中度、重度组血清及脑脊液IL-1β及NSE水平均明显高于对照组,且随着病情程度的加重,血清及脑脊液IL-1β及NSE水平均呈升高趋势,血清及脑脊液IL-1β及NSE水平与患者病情程度具有明显相关性。脑脊液中IL-1β及NSE水平均高于血清(P0.05)。结论颅脑损伤后患者血清及脑脊液IL-1β及NSE水平可反映颅脑损伤程度,可作为判断颅脑损伤患者预后的敏感指标。     

PTZ致痫大鼠海马区神经元损伤的研究

目的:为了解癫痫(Epilepsg,EP)发生后大脑海马区的损害情况,本文采用戊四氮诱导建立大鼠癫痫模型, 采用酶标免疫吸附法(EIA)和免疫组化染色法检测NSE的改变,使用电子显微镜研究超微结构的改变,探讨EP后脑组织的损坏情况。方法:雄性SD大鼠54只,随机分为对照组(A=13)及实验组(41只)。实验组腹腔注射(IP)PTZ 50mg/ kg体重1次,对照组IP生理盐水。根据EP发作分级,0-1级7只,视为B组,立即取脑:2级以上发作34只,随机抽样于EP发作后0h(C=10);6h(D=14);24h(E=10)断头。取脑前抽取躯干血,分离海马。A、D组随机抽取3只进行电镜观察。采用EIA法测试血清和海马NSE-值;以S-P免疫组化染色法染色,观察各组大鼠海马的NSE表达。结果:实验组海马和血清的NSE均明显高于对照组:即使无EP大发作,但有兴奋症状的大鼠,NSE亦高于对照组,表明也有脑组织损害。免疫组化染色显示:对照组海马组织几乎未见NSE的表达,即大发作后海马的NSE表达明显增加,但随时间推移而降低。电镜观察发现EP后大鼠海马CA1区的神经元细胞出现水肿、基质密度变淡、微丝溶解消失、细胞器减少、毛细血管周围间隙扩大等明显改变。结论:EP发作对大鼠海马区神经细胞造成了明显的损害。     

白藜芦醇对戊四氮致痫大鼠脑脊液、血清S1OOB蛋白的影响

目的 研究白藜芦醇(Res)对戊四氮致痫大鼠脑脊液、血清S100B蛋白的影响.方法 采用戊四氮(PTZ)腹腔注射建立慢性癫痫模型,造模成功后予以Res(15 mg/kg·d)灌胃干预10 d;采用酶联免疫吸附法测定脑脊液、血清S100B蛋白含量,海马标本行Nissl染色.结果 经28 d连续给药,18只大鼠符合Racine点燃标准,Res干预组大鼠痫性发作潜伏期明显延长,且发作时间明显低于癫痫模型组、二甲基亚砜组(P＜0.05).海马Nissl染色提示Res干预对大鼠海马CA1、CA3区神经元有保护作用(P＜0.05),而对齿状回保护作用不明显(P＞0.05).Res干预组大鼠脑脊液、血清S100B蛋白含量低于癫痫模型组、二甲基亚砜组(P＜0.05).结论 Res降低PTZ致痫大鼠脑脊液、血清S100B蛋白含量,或许减缓癫痫发作脑损伤发挥神经保护作用.     

颅脑损伤患者血清NSE的含量变化及临床意义

目的动态监测颅脑损伤患者血清神经元特异性烯醇化酶(NSE)的含量变化,并探讨NSE与颅脑损伤程度及其预后之间的关系。方法用酶联免疫测定法检测86例颅脑损伤患者的血清NSE含量,并分析其与颅脑损伤严重程度及患者预后的关系。结果颅脑损伤患者血清NSE水平明显高于对照组(P<0.05);重度颅脑损伤患者血清NSE水平又明显高于中、轻度颅脑损伤者(P<0.05);重度颅脑损伤预后不良者的血清NSE水平则明显高于预后良好者(P<0.05)。结论血清NSE水平与脑损害的严重程度呈正相关,可作为评估颅脑损伤预后的重要指标。     

癫大鼠血清、海马组织中神经元特异性烯醇化酶和S-100β蛋白的变化及其临床意义

目的探讨红藻氨酸(KA)诱导癫疒间大鼠血清及海马组织中神经元特异性烯醇化酶(NSE)和S100β蛋白(S100β)的变化及其临床意义。方法180只Wistar大鼠随机分为对照组、KA组和卡马西平(CBZ)组,后两组再按癫疒间发作后1h、4h、12h、24h、48h和72h不同时点分为6个亚组。以放射免疫法(RIA)和酶联免疫吸附试验(ELISA)分别测定大鼠血清和海马匀浆液中NSE和S100β的变化。结果癫疒间发作72h内,血清和海马匀浆液中NSE和S100β的含量是一个动态变化过程,且呈同步变化的趋势,在12h时均达到峰值。在4～48h时,KA组和CBZ组的二者含量均明显高于对照组(P<0.05～0.01)。结论癫疒间发作后NSE和S100β的含量升高,二者可作为癫疒间发作后脑组织损伤的一个参考指标。     

生酮饮食对幼鼠戊四氮诱导痫性发作的影响及海马CA3区形态学观察

目的　探讨生酮饮食 (KD)对幼鼠戊四氮 (PTZ)诱导痫性发作阈值的影响及海马结构的病理改变。方法　通过尾静脉输注 PTZ,测定 KD饲料和普通饲料喂养两组 Wistar幼鼠的痫性发作阈值 ,并对其抽搐行为进行评分 ,同时对致痫后两组幼鼠海马 CA3区的病理学改变进行观察。结果　KD组幼鼠 PTZ诱导的痫性发作阈值明显高于对照组 (P <0 .0 1 ) ,但两组痫性发作的强度差异无显著性 (P >0 .0 5 )。 KD组幼鼠海马 CA3区正常锥体细胞计数较对照组明显增多 ,神经元损伤程度较轻。结论　KD可提高幼鼠 PTZ诱导的痫性发作阈值 ,但不影响发作强度 ;KD可减少痫性发作次数 ,对致痫幼鼠具有神经保护作用。     

唑尼沙胺对戊四氮致痫小鼠认知功能的影响

目的探讨唑尼沙胺(ZNS)对癫痫小鼠的认知功能影响及抗癫痫作用。方法利用戊四氮(PTZ)致痫小鼠模型,通过Morris水迷宫实验、神经元特异性烯醇化酶(NSE)及海马组织形态学的改变,观察ZNS对癫痫小鼠的认知功能影响及抗癫痫作用。结果正常组小鼠无惊厥发作,血清NSE水平在正常范围,海马组织结构正常;癫痫组惊厥出现时间早,发作程度重,血清NSE水平明显高于其它两组,海马组织结构紊乱、疏松;ZNS组惊厥出现时间晚,发作程度轻,血清NSE水平略高于正常组而显著低于癫痫组,海马组织结构无显著变化。结论 ZNS有明确抗癫痫作用,通过控制癫痫发作,有效的改善致痫小鼠的认知功能。     

癫痫患者血清和脑脊液神经元特异性烯醇化酶的测定

目的 探讨癫痫发作对脑神经元的损伤。方法 应用酶联免疫反应法动态测定癫痫发作后患者血清和脑脊液（CSF）中神经元特异性烯醇化酶（NSE）的含量。结果 癫痫组血清和CSF中NSE含量在发作后明显升高，血清NSE水平在发作后第1天最高，1周左右开始下降，2周左右降至正常；抽搐发作及频繁发作时，血清和CSF中NSE升高更明显。结论 癫痫发作引起血清和CSF中NSE水平的升高；癫痫发作导致神经元损伤，抽搐发作及频繁发作时神经元损伤更严重。     

Analysis of cerebrospinal fluid glial fibrillary acidic protein after seizures in children

PURPOSE: To evaluate pediatric seizure patients for astrocytic injury by measuring cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP), determine risk factors for GFAP elevation after seizures, and compare seizure-induced astrocyte injury with neuronal injury by concurrent measurement of CSF neuron-specific enolase (NSE). METHODS: CSF obtained from pediatric patients (n = 52) within 24 h of seizure was assayed for GFAP and NSE. Retrospective chart review was performed for seizure type, duration, and etiology. RESULTS: Overall, children with seizures had elevated CSF GFAP compared with controls (p = 0.0075), but no elevation of NSE (p = 0.1437). No effect of seizure type or etiology was found, but a significant positive effect of seizure duration (p = 0.0010) and status epilepticus (p = 0.0296) was seen on CSF GFAP. Individually, seven children (13%) had elevated GFAP (>440 pg/ml); in five children, the increased GFAP was not accompanied by elevations in NSE (<12 ng/ml). Five children with elevated GFAP had symptomatic etiologies for their seizures, but the etiology of one child with elevated GFAP was cryptogenic, and one had febrile seizures. CONCLUSIONS: Elevation of CSF GFAP after seizures suggests that astrocytic injury may occur in a subgroup of children, primarily in the context of prolonged seizures and symptomatic etiologies. Increased GFAP levels may occur in patients with normal NSE, suggesting that GFAP may be a more sensitive marker of brain injury in some cases.     

Cerebrospinal Fluid and Serum Neuron-Specific Enolase Levels After Febrile Seizures

PURPOSE: Neuron-specific enolase (NSE) has been established as a reliable marker of neuronal damage in various neurologic disorders. The aim of this study was to evaluate whether febrile seizures (FS) cause brain damage, based on the serum and cerebrospinal fluid (CSF) levels of NSE. METHODS: Fifty-three patients aged from 6 months to 7 years were enrolled. Among them, 36 patients had generalized seizures, and 17 had partial seizures. The maximal seizure duration was 90 min. Blood and CSF samples for measurement of NSE were obtained immediately after the seizure. NSE was measured using an enzyme immunoassay (EIA). RESULTS: Serum and CSF levels of NSE ranged up to 10 ng/mL, but very high levels were not observed. In patients with partial seizures, the NSE level in the CSF and the ratio of the CSF to serum NSE levels showed a strong correlation with seizure duration. Conversely, there were no correlations between NSE levels and seizure duration in the patients with generalized seizures. CONCLUSIONS: These results indicate that FS seldom cause severe neurologic damage, but prolonged partial seizures may cause slight neuronal injury.     

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic-clonic seizures

PURPOSE: Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic-clonic seizures to search for evidence of neuronal and glial damage. METHODS: 22 consecutive patients with single, previously undiagnosed and untreated tonic-clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. RESULTS: The mean CSF NSE was 8.9 ng/ml (range 0-28 ng/ml) and s-NSE 8.2 ng/ml (range 5-15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3-24 ng/ml) and 8.0 ng/ml (range 5-12 ng/ml) respectively. The mean CSF S-100 was 3.17 microg/l (range 1.45-7.02 microg/l) and serum S-100 0.05 microg/l (range 0-0.32 microg/l), and in controls 3.19 microg/l (range 1.52-5.13 microg/l) and 0.08 microg/l (range 0-0.28 microg/l). CONCLUSION: There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic-clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic-clonic seizures in unmedicated patients.     

不同发作类型癫痫患儿血清神经元特异性烯醇化酶水平研究

目的探讨不同发作类型癫痫患儿血清神经元特异性烯醇化酶水平变化与脑损害之间的关系。方法按照1981年国际抗癫痂联盟制定的癫痫发作类型分类标准,共明确诊断190例癫痫患儿（强直．阵挛发作41例、强直性发作34例、阵挛性发作22例、肌阵挛发作12例、无张力性发作17例、失神发作22例、单纯部分性发作21例及复杂部分性发作21例）,于癫痫发作72h内施行长程视频脑电图观察和血清神经元特异性烯醇化酶检测。结果不同发作类型癫痫患儿血清神经元特异性烯醇化酶水平均高于正常对照组（P=0．000）,其中以肌阵挛发作组[（32．42±6．62）ng／m1]水平最高,除与强直一阵挛发作组（P=0．062）外,与其他各发作类型之间差异均有统计学意义（P=0．000）;而其他各类型之间差异无统计学意义（均P〉0．05）。秩相关分析显示,癫痫患儿血清神经元特异性烯醇化酶水平与长程视频脑电图异常程度呈正相关（rs=0．613,P=0．000）。结论癫痫发作后血清神经元特异性烯醇化酶水平即升高,提示癫痫发作对患儿脑组织有一定损害;而且癫痫放电对神经元损害越严重、血清神经元特异性烯醇化酶水平升高越明显,不同发作类型中以肌阵挛发作、强直一阵挛发作患儿血清神经元特异性烯醇化酶水平最高,提示这两种发作类型对脑组织的损害高于其他类型。     

Serum and CSF neuron-specific enolase in patients with West syndrome

OBJECTIVE: To determine whether frequent seizures and/or hypsarrhythmia may cause neuronal injury in West syndrome. BACKGROUND: West syndrome is an age-related epileptic syndrome of infancy characterized by clusters of epileptic spasms, a peculiar interictal EEG pattern of hypsarrhythmia, and mental deterioration. Recent clinical studies demonstrated that serum and CSF neuron-specific enolase (NSE)-a marker of neuronal injury-were increased after status epilepticus. METHODS: The authors examined serum and CSF NSE levels in 18 newly diagnosed infants (8.4 +/- 2.2 months) with West syndrome (3 cryptogenic, 15 symptomatic). In patients who showed complete resolution of spasms and disappearance of hypsarrhythmia (responders), additional serum NSE levels were determined several weeks after cessation of seizures. Serum NSE levels were obtained from 28 age-matched infants with normal neurologic development (control group), and 10 infants with an acute neurologic insult. RESULTS: There were no significant differences (p > 0.05) in serum NSE levels between the group with West syndrome (12.9 +/- 3.4 ng/mL) and the control group (13.2 +/- 3.1 ng/mL). The serum NSE value in the group with an acute insult (100.3 +/- 67.4 ng/mL) was significantly higher (p < 0.0001) than that for the West syndrome and the control groups. The mean +/- SD CSF NSE level was 7.3 +/- 3.6 ng/mL, which is similar to the reported CSF NSE levels of Japanese infants without neurologic disease. Thirteen responders showed no significant (p > 0.05) change in serum NSE after cessation of epileptic spasms. CONCLUSION: Normal serum and CSF neuron-specific enolase levels provided no evidence that seizures and/or hypsarrhythmia induced neuronal injury in West syndrome.     

癫(癎)患者血清、脑脊液神经元特异性烯醇化酶的测定及意义

目的探讨癫癎患者癎性发作后对神经元和血脑屏障的损伤。方法采用酶联免疫法测定癫癎患者在癎性发作后2d内血清和脑脊液(CSF)中神经元特异性烯醇化酶(NSE)的含量,与非神经系统疾病的神经症对照组对比分析。结果患者组CSF中NSE较对照组升高,差异有统计学意义;但血清中NSE含量与对照组差异无统计学意义。结论癫癎患者癫癎发作后脑脊液中NSE升高,提示癎性发作对中枢神经的神经元有损伤;而血中NSE正常,提示血脑屏障正常。     

Kinetics of Serum Neuron-Specific Enolase and Prolactin in Patients After Single Epileptic Seizures

PURPOSE: To investigate and compare the temporal profile of serial levels of neuron-specific enolase (NSE) and prolactin in serum from patients after single epileptic seizures. METHODS: Measurement of NSE and prolactin by sensitive immunoassays in 21 patients with complex partial seizure (CPSs: n = 11) and secondarily generalized tonic-clonic seizures (SGTCSs; n = 10) during continuous video-EEG monitoring at four different time points (1, 3, 6, and 24 h after ictal event). Statistical analysis was performed by using a repeated-measures analysis of variance (ANOVA) model. RESULTS: Mean+/-SD values for NSE levels (ng/ml) were 12.5 +/-4.4 (1 h), 10.8+/-3.8 (3 h), 11.1+/-4.9 (6 h), and 8.2+/-1.9 (24 h). The corresponding prolactin levels (mU/L) were 1,311+/-1,034, 232+/-158, 237+/-175, and 251+/-98. There was a significant decrease of NSE and prolactin levels over time (p < 0.001). The pair-wise comparison of NSE levels showed significant differences between the time points 1 vs. 24 h (p < 0.001), 3 vs. 24 h (p = 0.007), and 6 vs. 24 h (p = 0.009). In contrast, serum prolactin levels showed a significant difference between 1 vs. 3 h (p < 0.001) only. Most of the NSE levels remained normal after CPSs and SGTCSs. At 1 h after the seizure, only 33% of the subjects had increased NSE, whereas abnormal prolactin levels occurred with a sensitivity of 80%. CONCLUSIONS: In contrast to prolactin, serum NSE is not a sensitive marker of individual seizures. Only some individuals showed an increase of NSE beyond the prolactin-sensitive time frame after a single seizure, and mean NSE levels were not significantly increased compared with those of normal controls.     

Inter-ictal and post-ictal circulating levels of allopregnanolone,an anticonvulsant metabolite of progesterone,in epileptic children

Allopregnanolone belongs to a group of neuroactive steroid hormones, or neurosteroids, synthesized and acting within the brain and is as a potent endogenous positive modulator of GABA(A) receptor complex. Administration of allopregnanolone protects rats against pentylentetrazol, bicuculline, kainic acid, and picrotoxin-induced seizures. We investigated serum allopregnanolone levels in children with active epilepsy at pubertal Tanner's stage I (n=52). Blood specimens were collected at least 12 h after a seizure (inter-ictal). In a subgroup of patients (n=11), specimens were also collected within 30 min from a seizure attack (post-ictal). Healthy age-matched children (n=18) served as controls. Serum allopregnanolone was measured by radioimmunoassay using a polyclonal antiserum. The inter-ictal serum allopregnanolone levels in the epileptic children were not statistically different from those detected in the control group, whereas post-ictal levels were significantly higher than the inter-ictal ones (P=0.0001). In this subgroup of patients allopregnanolone levels decreased to the basal values during the following 12 h. Serum allopregnanolone levels may therefore reflect changes in neuronal excitability, and allopregnanolone appears to be a reliable circulating marker of epileptic seizures. It is possible that increased post-ictal serum levels of allopregnanolone may play a role in modulating neuronal excitability and may represent an endogenous mechanism of seizure control.