Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy

In patients at risk of developing epilepsy after an initial precipitating injury to the brain, the epileptogenic latent period may offer a window of opportunity for initiating potential antiepileptogenic therapy in an attempt to prevent epilepsy from developing. One potential target for antiepileptogenesis is the development of neuronal hyperexcitability during the latent period. Surprisingly, some recent studies in models of temporal lobe epilepsy (TLE) have suggested that proconvulsant drugs could have favourable effects on epileptogenesis, resulting in the proposal of pursuing proconvulsant prophylaxis for epileptogenesis. In the present study, we evaluated this provocative hypothesis by experiments with the GABA(A) receptor antagonist pentylenetetrazole (PTZ) in two TLE models, the intrahippocampal kainate model and the lithium-pilocarpine model in rats. First, we repeatedly determined the PTZ seizure threshold by i.v. infusion of the convulsant during the latent period following intrahippocampal kainate. In line with recent experiments in the lithium-pilocarpine model, the PTZ seizure threshold was significantly decreased over several days following status epilepticus. We then studied whether prolonged infusion of a proconvulsant dose of PTZ at different times after kainate or pilocarpine affected the development of epilepsy. PTZ did not prevent the development of spontaneous recurrent seizures and did not decrease their frequency or severity, but exerted only a moderate disease-modifying effect in that spontaneous seizures in the kainate model were significantly shortened. These data indicate that administration of proconvulsant drugs such as PTZ during the latent period following SE is not a promising strategy for preventing epilepsy.     

戊四氮致痫大鼠脑脊液神经元特异性烯醇化酶的水平测定

目的通过测定戊四氮致痫大鼠脑脊液中的神经元特异性烯醇化酶(NSE)水平的变化,探讨痫性发作与脑损伤之间的关系。方法110只Wistar大鼠分为实验组和对照组。实验组给予戊四氮(PIZ)腹腔注射。根据痫性发作的强度分为轻度组和重度组。用酶联免疫吸附法(ELISA)测定不同痫性发作强度、不同时间点大鼠脑脊液中NSE水平的变化,并与对照组进行对比。结果重度组脑脊液NSE水平在1h、2h、4h、6h均显著高于轻度组和对照组(P<0.01);轻度组脑脊液NSE含量在1h高于对照组(P<0.05),在2h、4h、6h显著高于轻度组;脑脊液NSE水平在痫性发作后1h迅速升高。4h达到高峰,24h恢复到正常水平。结论痫性发作可对大鼠神经细胞造成明显的损害。损害的程度与痫性发作的程度有关。痫性发作后4h可能是进行早期干预、防止脑细胞损伤的时间窗。     

The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats

Experimental studies have demonstrated that free radicals play a major role on neuronal injury during ischemia/reperfusion (I/R) in rats. Erdosteine is a thioderivative endowed with mucokinetic, mucolytic and free-radical-scavenging properties. The aim of the present study was to investigate the effect of erdosteine treatment against short-term global brain ischemia/reperfusion injury in rats. The study was carried out on Wistar rats divided into four groups. (i) Control group, (ii) ischemia/reperfusion group, (iii) ischemia/reperfusion+erdosteine group, and (iv) erdosteine group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as thiobarbituric acid reactive substances (TBARSs) and nitric oxide (NO) levels were analysed in erythrocyte and plasma of rats. Plasma NO levels were significantly higher in the ischemia/reperfusion group than the other groups. The activities of SOD and GSH-Px were decreased, while TBARS levels increased in the ischemia/reperfusion group compared to other groups in both plasma and erythrocyte. The erythrocyte CAT activity was higher in erdosteine group and there was a statistically significant increase, when compared with the erdosteine plus ischemia/reperfusion group. By treating the rats with erdosteine, the depletion of endogenous antioxidant enzymes (SOD, CAT, GSH-Px) and increase of TBARS and NO levels were prevented. This study, therefore, suggests that erdosteine reduces parameters of oxidative stress is well supported by the data.     

NMDA-induced seizures in developing rats cause long-term learning impairment and increased seizure susceptibility

N-methyl-D-aspartate (NMDA) receptors play a prominent role in the pathogenesis of epilepsy, yet few studies have used NMDA as a convulsant in whole animals. In developing rats, systemic NMDA induces seizures with a unique seizure phenotype ("emprosthotonic" or hyperflexion seizures) and electrographic pattern (electrodecrement). These features are not seen in kainic acid-induced seizures, suggesting that seizures activated by NMDA might cause different long-term consequences. Therefore, we investigated the effects of NMDA seizures during development on cognitive function and susceptibility to seizures in adulthood. Rat pups (P12-20) were injected with saline (n=36) or NMDA (n=64) at convulsant doses (15-30mg/kg, i.p.). After NMDA injection, a characteristic sequence of seizure activity was seen: initial behavioral arrest, followed by hyperactivity, agitation, and then emprosthotonus and generalized tonic-clonic seizures. Seizures were terminated 30min later by ketamine (50mg/kg, i.p.). On P85, rats underwent behavioral testing in the water maze. Rats that had experienced NMDA seizures as pups took significantly longer to learn the platform location over 5 days of testing, compared to controls. On P90, rats were injected with pentylenetetrazol (PTZ, 50mg/kg, i.p.) to assess their susceptibility to generalized seizures. NMDA-treated rats had decreased latency and increased duration of class V PTZ seizures. Cresyl violet-stained sections of cortex and hippocampus had no obvious cell loss or gliosis. In summary, NMDA causes a unique seizure phenotype in the developing brain, with subsequent deficits in spatial learning and an increased susceptibility to PTZ seizures in adulthood. This study provides additional evidence for long-term alterations of neuronal excitability and cognitive capacity associated with seizures during development.     

Effects of Ganoderma lucidum spore powder on astrocyte expression and glutamine synthetase activity in the hippocampal region of epileptic rats

BACKGROUND： Recent studies have demonstrated that astrocyte dysfunction plays a central role in inhibiting epileptic seizures and that regulation of astrocyte function may be a new target for treatment of epilepsy. OBJECTIVE： To observe the effects of Ganoderma lucidum spore powder （GLSP） on astrocyte morphology and glutamine synthetase （COS） activity in the hippocampal region of epileptic rats. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Function Laboratory, College of Basic Medicine, Jiamusi University between October and December 2006. MATERIALS： A total of 30 Sprague Dawley （SD） rats were randomized to three groups （n = 10）： control, model, and GLSP. GLSP was sourced from Jiamusi Wild Ganoderma Lucidum Planting Base and prepared to 30 g/L with physiological saline before use. Pentylenetetrazol （PTZ） （10 g/L） was provided by Sigma Company, USA. METHODS： The control group received intraperitoneal （i.p.） and intragastric （i.g.） physiological saline. Following epilepsy induction by i.p. administration of PTZ （35 mg/kg）, rats from the mode/and GLSP groups were ig injected with physiological saline and GLSP （300 mg/kg）, respectively. Each compound was administered once per day, for a total of 28 successive days. Epileptic seizure convulsions were graded 0-5. A higher grade indicated more severe epilepsy. Only those rats showing stage 2 or higher convulsions at least 5 times successively were included in further experiments. MAIN OUTCOME MEASURES： Immediately alter injection, seizure activity was monitored for 30 minutes to determine the latent period and seizure duration; simultaneously, astrocyte numbers and GS activity in the hippocampal region of rats with epilepsy were detected by immunohistochemistry. RESULTS： All 30 rats were included in the final analysis. On day 28, following PTZ administration epileptic seizures were not found in the control group. In the GLSP group, rats exhibited rhythmic head nodding or     

戊四氮致痫大鼠不同脑区神经肽Y的表达及意义

目的研究神经肽Y(neuropeptideY,NPY)在戊四氮(pentylenetetrazol,PTZ)致痫大鼠不同脑区中的变化,以探讨NPY与癫痫的关系。方法清洁级近交系雄性SD大鼠50只,分为对照组(A组,n=10)及实验组(40只)。实验组按体重50mg/kg经腹腔注射PTZ1次,对照组腹腔注射同等容量的生理盐水。根据癫痫发作分级,0~1级7只为B组,立即取脑;2级以上发作33只,随机于癫痫发作后0(C组,n=10)、6(D组,n=11)、24(E组,n=10)、72h(F组,n=2)取脑。采用放射免疫方法动态观察脑组织中海马、中脑、纹状体和额叶中NPY的改变;SP免疫组化染色法染色,观察各组大鼠海马CA1区NPY的表达。结果B组中脑、纹状体及额叶NPY含量较A组升高(P<005),而两组间海马NPY含量差异无显著性;癫痫发作组(C组、D组、E组)各部位NPY含量均明显高于A组。动态观察结果显示,癫痫发作后在中脑、海马、纹状体和额叶的NPY含量明显增高随后呈逐步下降,在癫痫发作后24h其含量与未发生惊厥的B组NPY含量差异无显著性(P>005);免疫组化染色显示癫痫大发作后海马NPY的表达明显增加,但随着时间的推移而降低。结论NPY与大鼠癫痫的发生、发展有密切关系。     

Neuronal Migration Disorders Increase Susceptibility to Hyperthermia-Induced Seizures in Developing Rats

Summary: Purpose: Retrospective studies suggest that adult patients with intractable epilepsy may have a history of febrile seizures in childhood. Risk factors for a febrile seizure may include the rate of increase in the core temperature (T-core), its peak (T_max), the duration of the temperature increase, or an underlying brain pathology. Recently, neuronal migration disorders (NMD) have been diagnosed with increasing frequency in patients with epilepsy, but the link between NMD, febrile seizures, and epilepsy is unclear. We studied rat pups rendered hyperthermic to ascertain the incidence of seizures, mortality, and extent of hippocampal cell loss in each group. Methods: We exposed 14-day-old rat pups with experimentally induced NMD (n = 39) and age-matched controls (n = 30) to hyperthermia (core body temperature >42°C). Results: The incidence of hyperthermia-induced behavioral seizures and mortality rate were significantly higher in rats with NMD than in controls (p < 0·05). The longer duration of hyperthermia resulted in a higher incidence of behavioral seizures and higher mortality rate (p < 0·05). In rats with NMD, hyperthermia resulted in hippocampal pyramidal cell loss independent of seizure activity; the extent of neuronal damage correlated positively with the duration of hyperthermia. In control rats, occasional neuronal loss and astrocytosis occurred only after prolonged hyperthermia. Conclusions: In immature rats, NMD lower the threshold to hyperthermia-induced behavioral seizures and hyperthermia in the presence of NMD may cause irreversible hippocampal neuronal damage.     

Antiepileptic activity of melatonin in guinea pigs with pentylenetetrazol-induced seizures

Abstract

Background: Antiepileptic and neuroprotective effects of melatonin (N-acetyl-5-methoxytryptamine) have been shown at higher doses (50–160 mg/kg). We aimed to investigate the antiepileptic effects of low-dose melatonin (10 mg/kg) on pentylenetetrazol (PTZ)-induced experimental epilepsy model.

Materials and Methods: Twelve male albino guinea pigs weighing 500–800 g were used in our work. Initially, latent period, seizure intensity and mortality parameters were evaluated during the epileptic seizure induced by PTZ. After a recovery period of 7 days, effects of the neuroprotective agent, melatonin (which is dissolved in 2.5% ethanol–saline solution), on epileptic seizures induced by PTZ were evaluated. Effects of 2.5% ethanol, which is an anticonvulsant agent when administered acutely in high concentrations, on PTZ-induced seizures were also evaluated.

Results: Data obtained from the study groups (PTZ, PTZ + melatonin and PTZ + ethanol) were evaluated by paired t-test, and p<0.005 was considered statistically significant. The differences of latent periods between the PTZ and PTZ + melatonin groups were found to be statistically significant (p<0.001).

Conclusion: Although melatonin does not have a primary anticonvulsant effect at low doses (10 mg/kg), it lowers the mortality rates and attenuates seizure severity while increasing the latent period.     

促红细胞生成素在脑缺血再灌注损伤中对线粒体的保护作用

目的 探讨促红细胞生成素(EPO)在脑缺血再灌注损伤中对线粒体功能的保护作用. 方法 30只SD大鼠按随机数字表法分为正常对照组、缺血再灌注组和EPO治疗组3组,每组各10只.EPO治疗组和缺血再灌注组用线栓法复制脑缺血再灌注模型.EPO治疗组在缺血再灌注后1、24、48、60 h腹腔注射EPO,剂量为3000 U/kg(用生理盐水以1:1比例稀释),缺血再灌注组腹腔注射同等剂量的生理盐水.正常对照组仅分离颈部动脉,动脉不做栓塞处理.缺血后72h观察各组大鼠脑组织神经细胞线粒体跨膜电位、线粒体丙二醛、超氧化物歧化酶、Na十_K+.ATP酶活性、一氧化氮含量和免疫组化检测海马区Caspase-3阳性细胞数的变化. 结果 EPO治疗组的神经细胞线粒体跨膜电位(77.48±5.93)、超氧化物歧化酶[(96.91±8.66)p,kat/g]、Na+_K+-ATP酶活性[(10.48±2.77)μkat/g]明显高于缺血再灌注组[44.47±17.35、(84.46±8.54)μkat/g、(7.37±2.87)μkat/g],线粒体丙二醛[(37.99±5.38)μmol/g]、一氧化氮含量[(10.18±2.02)μmol/g]、Caspase-3阳性细胞数(66.31±8.09)明显低于缺血再灌注组[(44.83±6.48)μmol/g、(12.12±2.14)μmol/g、74.90±7.42]. 结论 EPO对缺血再灌注损伤脑组织产生保护作用的重要机制之一是保护神经细胞线粒体的功能,其核心是抑制线粒体跨膜电位的下降.     

美解眠诱发癫痫大鼠大脑皮质NO和SOD的变化研究

目的：观察癫痫大鼠脑中的一氧化氮（NO）和超氧化物歧化酶（SOD）的变化,并探讨NO的氧化还原状态对癫痫的作用。方法：通过美解眠诱发致痫的大鼠模型,分别取癫痫发作时及癫痫发作刚停止时的大脑运动区皮质,匀浆后测定NO的含量和SOD活力。结果：癫痫发作组及癫痫发作刚停止组,大脑运动皮质的NO含量均较正常对照组明显升高;癫痫发作组,脑内SOD活力反而下降,癫痫发作刚停止组,脑内SOD活性力明显升高,结论：癫痫发作组和短暂发作刚停止组,SOD活力／NO含量比值具有显著差异,这些结果支持NO的不同氧化还原状态在癫痫发作中起到不同的作用。     

Parenteral magnesium sulfate fails to control electroshock and pentylenetetrazol seizures in mice

Magnesium sulfate has been used as an anticonvulsant in the treatment of eclampsia, but efficacy of magnesium in other types of seizure disorders is poorly documented. We examined the effects of magnesium sulfate (MgSO4) on seizures produced in mice by maximal electroshock (MES) and pentylenetetrazol (PTZ), MgSO4 injection (6.7 mEq/kg i.p.) caused weakness in all animals. With suprathreshold electroshock, 10/10 controls and 11/12 treated animals had seizures with tonic hind limb extension (P = NS). Electroshock threshold was unaltered by magnesium treatment (n = 48; P = 0.47). PTZ induced clonic seizures in 12/12 controls and 5/14 treated animals (P less than 0.05). This difference was likely due to muscular weakness because frequency of EEG spikes was the same in PTZ and PTZ + MgSO4 groups. Mean serum magnesium levels were 2.3 +/- 0.3 mEq/l in animals not given MgSO4; 10.9 +/- 1.4 mEq/l and 12.8 +/- 2.2 mEq/l in treated animals with and without seizures (P = NS). We conclude that magnesium sulfate had no significant anticonvulsant activity in mouse MES and PTZ models for epilepsy. The relevance of these findings to the possible efficacy of magnesium sulfate in eclamptic seizures and other types of epilepsy remains to be determined.     

The role of superoxide dismutase and alpha-tocopherol in the development of seizures and kindling induced by pentylenetetrazol - influence of the radical scavenger alpha-phenyl-N-tert-butyl nitrone

Previous experiments have shown that the generation of free hydroxyl radicals in rat brain homogenates is increased following pentylenetetrazol (PTZ) kindling. The present study was performed in order to evaluate the involvement of endogeneous radical defence systems as the superoxide dismutase (SOD) and the level of alpha-tocopherol, an important lipid-soluble and membrane-bound antioxidant in brain homogenate of rats after acute seizure and kindling induced by PTZ. The activities of the total SOD were significantly reduced after acute seizure and tend towards an enhancement in kindled animals. Western blot analysis shows an upregulation of Mn-SOD in rat brain homogenates after kindling. The level of the chain-breaking antioxidant alpha-tocopherol was reduced in acutely convulsing rats and was not modified in kindled rats. Second, we studied the influence of exogeneously supplied radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN) on seizure and kindling following PTZ treatment. After a single injection of PTZ at a dose evoking clonic-tonic seizures, PBN did not modify either the formation of free hydroxyl radicals measured by the levels of 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA or the susceptibility to PTZ. In the kindling group, subchronic treatment with PBN (over a period of 4 weeks) prevented the increase in the formation of free hydroxyl radicals, and the susceptibility to PTZ was transiently decreased during the development of kindling, but PBN did not influence the susceptibility to PTZ in fully kindled rats. Pretreatment with PBN increased the activities of total SOD and the protein content of Mn-SOD and decreased the level of alpha-tocopherol in comparison to saline controls. The results suggest that the formation of free hydroxyl radicals is not reflected by an enhanced susceptibility to PTZ classified according to the modified RACINE scale. Additionally, it may be assumed that the increased generation of hydroxyl radicals in kindled animals is not primary caused by an exhaustion of both the defence systems measured. Adaptive mechanisms, as the induction of Mn-SOD, may be taken into consideration to counteract oxidative stress-mediated free radical formation.     

养血清脑颗粒和丙戊酸联用对戊四氮点燃癫痫大鼠的影响

目的 探讨养血清脑颗粒(YXQNG)联用丙戊酸(VPA)对戊四氮(PTZ)慢性点燃模型大鼠癫痫发作、EEG、认知功能及颞叶、海马T型Ca2+通道蛋白(Cav3.2)表达的影响. 方法 成年雄性SD大鼠40只按随机数字表法分为PTZ组、VPA组、VPA+YXQNG组、NS组,每组10只.前3组大鼠腹腔注射PTZ溶液制作慢性点燃模型,VPA组大鼠在注射PTZ前1 h给予VPA灌胃;VPA+YXQNG组除给予VPA外,注射PTZ前1.5 h给予YXQNG灌胃;NS组腹腔注射生理盐水,每天一次.8周后观察各组大鼠的行为学变化、Y型电迷宫检查大鼠的正确反应率、捕记EEG并应用免疫组化染色检测颞叶和海马Cav3.2的表达. 结果 给药8周后PTZ组大鼠全部达到完全点燃(连续3 d出现Ⅳ级发作或达到Ⅴ级发作),VPA组和VPA+YXQNG组大鼠仅出现0～Ⅱ级发作;Y型电迷宫检查结果显示VPA+YXQNG组大鼠正确反应率高于PTZ组,差异有统计学意义(P＜0.05);EEG结果显示PTZ组大鼠癫痫发作时EEG有明显异常放电,总功率高于用药前,差异有统计学意义(P＜0.05).VPA组、VPA+YXQNG组大鼠用药前后EEG总功率的差值均高于PTZ组,差异有统计学意义(P＜0.05);免疫组化染色结果显示VPA组、VPA+YXQNG组大鼠颞叶和海马Cav3.2表达低于PTZ组,VPA+YXQNG组大鼠颞叶和海马Cav3.2表达低于VPA组,差异均有统计学意义(P＜0.05). 结论 YXQNG和VPA联用能降低癫痫大鼠发作级别、改善认知功能、减少脑部异常放电并降低脑组织Cav3.2水平,有抗癫痫和脑保护作用.

Abstract：

Objective To explore the effet of Yangxue Qingnao granule (YXQNG) on seizures and cognition function of pentylenetetrazole (PTZ)-kindled chronic epileptic rats models, expression of Cav3.2 in the hippocampus and the temporal lobe of these rats, and EEG features of the rats. Methods Forty healthy adult male SD rats were equally divided into 4 groups at random: PTZ group, VPA treatment group, VPA+YXQNG treatment group, normal saline (NS)-control group (n=10). PTZ solution was intraperitoneally injected for 8 weeks to induce the kindling model in the above 3 groups except the NS-control group. VPA by intragastric administration was given to the rats in the VPA treatment group 1 h before PTZ injection; YXQNG and VPA by intragastric administration were given to the rats in the VPA+YXQNG treatment group 1.5 h before PTZ injection. Behavioral changes of the rats were observed 8 weeks after PTZ injection; accuracy rate of response of the rats were examined by electric maze test;EEG was performed; and the expression ofT-type Ca2+ channel protein (Cav3.2) in the temporal lobe and hippocampus was detected by immunohistochemical staining. Results Rats in the PTZ group appeared grade Ⅳ or Ⅴ seizures for 3 consecutive d, and rats in the VPA treatment group, VPA+YXQNG treatment group appeared grade 0-Ⅱ seizures. The accuracy rate of response of the rats in the VPA+YXQNG treatment group was significantly higher than that in the PTZ group (P＜0.05). EEG indicated that paradoxical discharge was noted in rats of PTZ group when seizures appeared, and the total power at the time was obviously higher than that before PTZ injection (P＜0.05). The D-value of total power of EEG in rats of the VPA treatment group and VPA+YXQNG treatment group before and after treatment was significantly higher than that in the PTZ group (P＜0.05). And the level of Cav3.2 in the temporal and hippocampus in rats of the VPA treatment group and VPA+YXQNG treatment group was significantly lower than that in the PTZ group (P＜0.05); as compared with that in the VPA treatment group, the expression of Cav3.2 in the temporal and hippocampus in rats of the VPA+YXQNG treatment group was significantly reduced (P＜0.05). Conclusion The combination use of YXQNG and VPA can decrease the seizure stage, the paradoxical discharge of the brain and the level of Cav3.2 in brain tissue,and improve the cognitive function of the PTZ-kindled rats, indicating that using VAP and YXQNG simultaneously can treat epileptic seizure and protect the neurons.     

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。     

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.     

Significance of chronic epilepsy in glial tumors and correlation with surgical strategies.

PURPOSE: This study was designed to compare the frequency of postoperative epilepsy in patients with acute and chronic pre-operative epilepsy and with frontal or temporal lobe glial tumors based on the hypothesis that patients with chronic epilepsy do worse. METHODS: We compared the clinical and diagnostic characteristics of the patients (n = 73) who had seizures preoperatively with those of the patients (n = 153) who did not. Among those who have had seizures preoperatively, we compared those (n = 32, chronic seizure group) who had seizures a year or more prior to surgery with those (n = 41, acute seizure group) who had seizures less than a year prior to surgery. RESULTS: Among the various factors, the frequency of benign pathology and favorable neurological state were higher in the seizure group than in the non-seizure group (p < 0.05). Complex partial seizures and low-grade tumors were frequent in the chronic seizure group, whereas simple partial seizures and high-grade tumors were frequent in the acute seizure group. Seizure-free rate was significantly higher in the acute seizure group than in the chronic group (p < 0.05). Also, the difference of seizure control rate between surgical strategies was statistically significant (p < 0.05). CONCLUSION: This study indicates that preoperative seizure duration and frequency have a close relationship with the frequency of postoperative epilepsy in patients with glial tumors. A longer duration may allow the formation of epileptogenic foci, leading to chronic epilepsy, and eventually have a negative effect on the prognosis of the patients. Factors including histopathological characteristics of the tumor, its location, seizure duration/frequency, and symptomatology should be taken into account when deciding on surgical strategies.     

雷帕霉素对未成年癫痫模型大鼠的毒性作用

目的利用戊四氮(pentylenetetrazol,PTZ)慢性点燃Sprague Dawley大鼠(SD大鼠)模型观察在点燃初期腹腔注射雷帕霉素(rapamycin,RAPA)能否抑制癫痫发生以及雷帕霉素在治疗中的安全性。方法将6~8周龄SD雄性大鼠随机分为雷帕霉素干预组PTZ+RAPA及其对照组PTZ+NS(normal saline)及NS组,观察1周(w)、2周(w)、4周(w)、6周(w)共4个时间点,每亚组12只,观察实验动物体质量的变化、死亡率及癫痫发作情况。结果各组实验大鼠的死亡率:PTZ+RAPA组为22.9%,PTZ+NS组为10.4%,NS组为0%。PTZ+RAPA组与PTZ+NS组各个相对应的时间点(1 w,2 w,4 w,6 w)体质量差均有统计学差异(P0.001)。6周时PTZ+RAPA组的点燃率为66.7%,PTZ+NS组的点燃率为58.3%,二者无统计学差异(P0.05)。PTZ+RAPA组与PTZ+NS组相对应时间点(1 w,2 w,4 w,6 w)发作分值的两两比较差异无统计学意义(P0.05)。结论雷帕霉素未能减少或抑制未成年大鼠的癫痫发作,但能明显降低未成年SD大鼠的体质量,可能有一定的毒副作用。     

Body part asymmetry in partial seizure

Clinically differentiating between localisation related and generalised epilepsy is important because it carries significant implications for planning diagnostic management strategy. Asymmetry of body parts such as toes, popliteal crease levels, thumbs, cubital crease levels, and forehead and facial structures, are common in patients with localisation related epilepsy syndromes. We retrospectively studied 337 patients with seizure disorders. Body part asymmetry was routinely documented. Fifty-six were excluded because of non-epileptic seizures, pure psychiatric disorders, non-epileptic neurological disorders, brain tumours and strokes. The relationship between clinically detectable body asymmetry (BA) and the electro-anatomic characteristics of their epilepsy was explored. Body asymmetry was found in 88 out of 282 cases, in which 64 (73.5%) suffered from localisation related epilepsy. Among localisation related epilepsy, BA were found in 41.5% (n=64/154) of patients. In contrast, only 18.75% (n=24/128) of patients with generalised seizure disorders showed similar findings (P<0.0001). Among patients with partial onset seizures, lateralisation of BA was concordant with their seizure origin in 75.9% (n=41/54) and discordant in 24.1% (n=13/54). Investigation results of 10 partial epilepsy cases were non-lateralising at the time of study. Peak age of onset of concordant case was 0-5 years old while discordant group was 6-15 years old. We conclude that BA in patients with seizure disorder is a useful clue to diagnosis of localisation related seizure and may provide clues for lateralising seizure origin in partial onset seizures.     

戊四氮点燃癫(癎)大鼠海马巢蛋白和骨形成蛋白-4的表达研究

目的观察巢蛋白(nestin)和骨形成蛋白4(BMP4)基因在戊四氮(PTZ)点燃癫大鼠海马中的表达,并探讨两者与癫发病机制的关系。方法将81只成年雄性SD大鼠随机分为实验组(n=54)和对照组(n=27)。实验组采用PTZ点燃癫大鼠,按点燃中的不同时相点,又随机分为9组。用免疫组化技术、地高辛标记特异性寡核苷酸探针原位杂交组织化学技术,观察海马nestin和BMP4表达的变化。结果nestin阳性细胞在PTZ注射后3d开始出现在齿状回、CA3区和CA1区,到7d达到高峰,以后逐渐减少。BMP4在PTZ注射后7d开始增多,在点燃后1d达到高峰,以后逐渐减少,主要分布在齿状回、CA3区和CA1区。结论PTZ点燃可引起海马内星形胶质细胞增生、活化和神经发生,这可能是癫海马组织胶质化、神经元可塑性的病理基础;BMP4可能在PTZ癫形成过程中起重要作用。     

神经外科患者癫痫反复发作处理分析

目的 探讨神经外科患者出现癫痫反复发作的临床特点、处理原则与方法.方法 回顾性分析沈阳军区总医院神经外科自2011年1月至6月收治的9例癫痫反复发作患者的临床资料,分析其加重的原因、发作特点及治疗方法和结果.结果 9例患者中3例合并胶质瘤、1例蛛网膜囊肿、1例海绵状血管瘤、1例脑软化灶;7例有癫痫病史,2例既往无癫痫病史;7例为额叶癫痫,2例颞叶癫痫.癫痫发作加重的原因:减药3例,新诊断的脑肿瘤2例,手术(颅内电极置入术)1例,原因不明3例.癫痫发作类型包括部分性发作与全面性发作,发作频率从间隔3min至间隔数小时发作一次.患者经给予多种抗癫痫药物联合用药治疗,包括口服与注射给药,癫痫得到控制,其中添加左乙拉西坦口服有较好的疗效.结论 神经外科患者出现癫痫反复发作多呈药物难治性,发作不易控制,其处理应使用对部分性癫痫发作有较好疗效的多种抗癫痫药物联合用药,剂量应高于常规初始剂量,包括静脉注射及肌注给药,以尽快控制癫痫发作.左乙拉西坦因口服吸收快、起效迅速及有较好的抗癫痫作用,对癫痫反复发作有较好的疗效.