Prolonged action of tuftsin on penicillin-induced epilepsy

Brain Research Institute, Russian Academy of Medical Sciences, Moscow. Institute of Biological Research, Belgrade, Yugloslavia. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 7, pp. 56–58, July, 1992.     

Enhancement of activity of an epileptogenic focus in the frog hippocampus by kynurenins and its depression by serotonin

Experiments on frogs with an epileptogenic focus produced by injection of 1000 units penicillin (0.4 l) into the primordial hippocampus showed that preliminary injection of two kynurenins — quinolinic acid (QA, 0.1 g) and kynurenin itself (K, 1 g) — into the region of the focus or their injection into an already functioning epileptogenic focus led to an increase in the frequency of interictal epileptiform discharges and of electrographic correlates of fits on the EEG. Anthranilic acid (AA, 5 g) had no effect on activity of the focus whereas serotonin (S, 1 g) and 5-methoxytryptamine (1 g) substantially depressed it. The provoking action of the kynurenins on epileptically predisposed brain neurons, it is suggested, may play an important role in the pathogenesis of epilepsy.Department of Pharmacology, Leningrad Pediatric Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 2, pp. 158–160, February, 1979.     

Changes in GABA-immunoreactive cell density during motor focal epilepsy induced by cobalt in the rat

Summary The distribution of GABA-immunoreactive cell bodies and terminals was studied using an anti-GABA serum during the development of chronic focal epilepsy induced by cobalt deposits onto the motor cortex of the rat. Cell counts of GABA-positive neurons were carried out in the epileptogenic area and correlated with the electrophysiological activity of the cobalt focus. In normal control rats, we identified GABA-immunoreactive somata and processes in the motor agranular cortex; they were multipolar or bipolar but never pyramidal and were present in all layers, especially in layer II. GABA-immunoreactive terminals were widely scattered in the neuropil and surrounded the unlabelled cell bodies. In the cobalt-treated animals, changes in the GABAergic innervation were observed during the development of the epileptic focus: decreases in the GABA-positive cell density and in the number of GABA-positive terminals were present before the onset of epileptic discharges and became more marked during the period of maximal spiking activity; a progressive return to normal values of GABA-positive cell density (except in the deep layers) as well as the reappearance of GABA positive terminals were associated with the extinction of the epileptic syndrome. Our observations suggest that the impaired inhibitory neurotransmission mediated by GABA plays a role in the development of the cobalt-induced epilepsy; moreover the recovery of GABAergic function which occurs during the extinction of the epileptic syndrome might imply a capacity for axonal regeneration of the GABAergic neurons.     

Afterpotentials following penicillin-induced paroxysmal depolarizations in rat hippocampal CA1 pyramidal cells in vitro

Epileptic discharges were induced by superfusion of rat hippocampal slices with penicillin. Under these conditions the neurons generated paroxysmal depolarization shifts (PDS) after electrical stimulation of Schaffer collaterals. The PDS were followed by large afterhyperpolarizations lasting about 2 s. The mechanisms causing these afterhyperpolarizations were studied in CA1 pyramidal cells. A late component of the after hyperpolarizations, which determined their overall duration, was blocked by intracellular application of EGTA and reduced by superfusion with 8-Br-cAMP. In the same neurons these drugs had a comparable effect on after hyperpolarizations following depolarizing current injections; it was therefore concluded that the late component of the PDS afterhyperpolarizations was caused by a slow Ca²⁺-activated K⁺ current. An initial fast component of PDS afterhyperpolarizations, which peaked about 60 ms after PDS onset, was reduced by EGTA but not affected by 8-Br-cAMP suggesting that the fast Ca²⁺-activated K⁺ current also contributed to the PDS afterhyperpolarizations. Superfusion of the slice with the -aminobutyric acid B receptor (GABA_B) antagonists phaclofen or 5-aminovalerate reduced the amplitude of the afterhyperpolarizations during the first 1000 ms but did not affect the late Ca²⁺-dependent component, indicating that a GABA_B-mediated K⁺ inhibitory postsynaptic potential (IPSP) contributed to the PDS afterhyperpolarization. Intracellular injection of Cl^– revealed that an early part of the afterhyperpolarizations lasting about 500 ms was Cl^–-dependent. This component was blocked by superfusion of the slices with bicuculline, suggesting that a GABA_A-mediated Cl^– IPSP contributed to the PDS afterhyperpolarization. The experiments show that different synaptic and intrinsic components with different time courses participate in the generation of PDS afterpotentials.     

癫痫病人不对称性δ、θ活动的地形图研究

利用BEAM分析技术,以50例正常人为对照,用Z值概率差异地形图,对83例部分性与全面性发作的癫痫病人脑电背景活动的δ与θ不对称性情况进行分析,并与其它结果比较后显示,BEAM对癫痫病人的不对称性δ、θ的检出率达72％,较EEG目测分析敏感,其显示的病变区与EEG目测分析、CT、SPECT结果大多符合,可用作痫灶的定侧定位,亦有助于全面性癫痫与部分性癫痫的鉴别。     

癫痫大鼠海马结构谷氨酸和nNOS神经元的动态变化

的：探讨谷氨酸(Glu)和一氧化氮(NO)二者在癫痫模型中的作用及其相关性。方法：戊四唑化学点燃癫痫大鼠，分为Ⅰ、Ⅲ、Ⅴ级组和Ⅴ级后24h组。采用免疫组织化学方法和图像分析技术。结果：(1)Ⅲ、Ⅴ级组Glu免疫反应阳性神经元数目和平均光密度值升高；但Ⅴ级比Ⅲ级组有所下降；Ⅴ级后24h组恢复到对照组水平。(2)Ⅴ级组和Ⅴ级后24h组nNOS免疫反应阳性神经元数目和平均光密度值升高。结论：戊四唑点燃癫痫模型中，随着点燃级别的进展，Glu的含量是呈先增加后减少的趋势，而NO的含量是逐渐增加的，提示二者在癫痫发作中既有相关性又有独立性。     

西酞普兰对戊四氮点燃癫痫大鼠行为学及海马5-HT能递质系统影响的在体微透析研究

为研究5-羟色胺(5-HT)能神经递质在癫痫形成过程中的变化及西酞普兰(CTP)对其的影响,本研究用CTP(1mg/kg.d灌胃)预干预1周后,对戊四氮(PTZ,30mg/kg.d,腹腔注射)点燃癫痫过程中的行为学及在不同时间点对大鼠海马进行微透析取样,经高效液相电化学检测技术在活体观察了30只自由活动大鼠5-HT及其代谢产物5-羟吲哚乙酸(5-HIAA)水平和5-HT转化率(5-HIAA/5-HT)的动态变化。结果显示:PTZ注射后在CTP组发作潜伏期延长,发作程度轻和点燃时间延长,发作死亡率降低。点燃早期,CTP组大鼠的海马5-HT水平升高,5-HT转化率降低,与对照组和PTZ组比较,有显著性差异(P<0.05);点燃晚期CTP组和PTZ组与对照组比较5-HT水平和5-HT转化率均显著降低(P<0.05)。本研究结果提示PTZ点燃过程中,早期CTP升高脑内5-HT水平,可能直接抑制了引起爆发放电的动作电位,而抑制发作;晚期脑内5-HT神经元丢失和受体减少,功能减退,而导致CTP的作用减退。     

The effects of levetiracetam on objective and subjective sleep parameters in healthy volunteers and patients with partial epilepsy

Levetiracetam is a novel antiepileptic drug which has recently been released as an adjunctive treatment for partial epilepsy. In the two studies reported here we examined the objective and subjective effects of levetiracetam on sleep in 12 healthy volunteers and 17 patients [16 who could be evaluated for electroencephalogram (EEG) recordings] with a history of partial epilepsy on stable carbamazepine monotherapy. The studies were of a similar double-blind crossover placebo-controlled design with subjects' sleep being recorded in their own homes. The results from the two studies showed considerable similarities. In both, levetiracetam produced an increase in the time spent in stage 2 sleep, which in the patient study was accompanied by a decrease in the time spent in stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM) latency. The subjective changes included reports that sleep was of a better quality with fewer awakenings and patients also reported that their sleep was more restful. Volunteers and patients did, however, feel less alert on waking in the morning. Therefore, both groups reported a decrease in awakenings after levetiracetam despite the finding from the EEG of no change in the actual number of awakenings. It may be concluded from both studies that levetiracetam does affect some indicators of subjective sleep perception, but does not influence objective sleep measures of sleep continuity. The results from the patient study during placebo add-on treatment also showed that patients on carbamazepine had a marked increase in SWS, an increase in stage 2 sleep and an increase in REM latency compared with healthy volunteers. Interestingly, levetiracetam also reduced bilateral epileptiform EEG activity, particularly in patients with more discharges.