戊四氮致痫大鼠脑组织NT-4的变化及百里香与薄荷精油的干预作用

目的观察戊四氮致痫大鼠脑组织神经营养因子-4（Neurotrophin-4,NT-4）的变化,利用百里香与薄荷精油制备雾化吸入剂进行干预治疗,研究癫痫的发病机理及精油的作用机制。方法健康雄性Wistar实验大鼠40只,随机分为正常对照组、癫痫模型组、精油治疗I组、精油治疗Ⅱ组、每组10只。模型组和治疗组均用致痫亚惊厥剂量的戊四氮（PTZ）腹腔注射制作Wistar大鼠慢性点燃模型。在低温条件下迅速取脑,通过免疫组化检测皮质区NT-4的变化。结果实验性癫痫大鼠模型制作成功,精油组和癫痫模型组实验动物均达到点燃标准,与癫痫模型组动物相比,精油组大鼠潜伏期劈显延长,但持续时间之间的差别没有显著性。免疫组化检测实验结果表明：癫痫模型组大脑皮质NT--4含量比正常对照组增加,差异显著具有统计学意义性（P〈0．05）;精油组NT-4含量比癫痫模型组增加,差异显著有统计学意义（P〈0．01）。结论精油能够增强NT-4的表达,减轻癫痫发作时神经系统的损伤,可能有抗癫痫作用。     

Effect of α-hexachlorocyclohexane on metabolism and excretion of pentetrazol (Cardiazol®) in the rat

Summary -Hexachlorocyclohexan (-HCH) has been shown to be a potent anticonvulsant when tested with pentetrazol. In the experiments reported here the question was examined whether or not the anticonvulsant properties of -HCH are based on an acceleration of pentetrazol breakdown in the rat.In this study the rat has been shown to metabolize pentetrazol extensively. The enzymatic activity is located in the microsomal fraction of the liver and requires NADPH and oxygen. It is inhibited by SKF-525 A and carbon monoxide. This is taken as evidence that P-450 containing mixed function oxidases are involved in the breakdown of pentetrazol.-HCH pretreatment leads to an acceleration of pentetrazol break-down by microsome preparations of about 140%. In vivo -HCH pretreated rats eliminate pentetrazol from brain and serum with a half life of 1.3 h, while this is 3.8 h in untreated rats.The earliest point in time at which -HCH pretreatment causes diminished brain levels of pentetrazol has been found 60 min after pentetrazol injection. Prior to this brain levels of pentetrazol were identically in untreated and -HCH-treated rats.As pentetrazol elicits convulsions within the first 30 min following oral or subcutaneous administration of a convulsive dose and -HCH is clearly active as an anticonvulsant under these conditions, the accelerated breakdown of pentetrazol cannot be the cause of the anticonvulsive action of -HCH.Supported by Deutsche Forschungsgemeinschaft.H. W. V. was the holder of a grant from Deutsche Forschungsgemeinschaft.     

戊四氮诱发癫痫大鼠海马齿状回颗粒细胞树突发芽

目的利用化学点燃大鼠癫痫模型,观察癫痫发作后大鼠海马齿状回颗粒细胞树突的形态学变化,探讨癫痫敏感性形成机制。方法利用戊四氮（PTZ）制作化学点燃大鼠癫痫模型。采用点燃成功后3d、7d两个时间点,应用神经元高尔基染色法,在光镜下观察和定量分析大鼠海马齿状回颗粒细胞的树突改变。结果颗粒细胞的形态学参数（树突总长度、树突分支点数、树突野最大伸展距离和树突棘密度）在PTZ点燃后3d时均显著降低（P〈0.05）,而在PTZ点燃后7d时明显回升,并明显高于生理水平（P〈0.05）。结论在PTZ点燃大鼠癫痫发作后,颗粒细胞树突出现明显的可塑性改变,并在PTZ点燃后7d时出现发芽现象,这可能与癫痫敏感性的形成有关     

Anticonvulsant action of allopregnanolone in immature rats

Anticonvulsant activity of allopregnanolone, a neurosteroid allosterically modulating GABA_A receptor was tested in a model of motor seizures elicited by pentetrazol in immature rats. Rats 7, 12, 18, 25 or 90 days old were pretreated with allopregnanolone in doses from 5 to 40 mg/kg i.p. and 15 min later pentetrazol was injected subcutaneously in a dose of 100 mg/kg. Rats were observed in isolation for 30 min. Allopregnanolone dose-dependently suppressed both generalized tonic–clonic and minimal clonic seizures with the highest efficacy in 12-day-old rats. Anticonvulsant action was least expressed in adult animals. Duration of anticonvulsant action tested after a dose of 20 mg/kg in 12- and 90-day-old rats demonstrated markedly longer effects in young rats. Allopregnanolone compromised motor performance of rats but duration of this unwanted effect in 12-day-old rats was shorter than duration of anticonvulsant action. This difference can be important for possible clinical use of neurosteroids.     

Durch Nicotin und Pentetrazol ausgelöste EEG-Veränderungen an normalen und hypothyreotischen Kaninchen

Summary Doses of nicotine and pentetrazol required for the elicitation of certain EEG changes were determined in normal and hypothyroid rabbits. Hypothyroidism was produced by pretreatment with sodium perchlorate, methylthiouracil or J¹³¹.For elicitation of hippocampal seizure discharges — a typical action of nicotine on the rabbit's EEG — significantly higher doses of nicotine are required in hypothyroid animals. In these animals, the nicotine-induced hippocampal theta rhythm which preceeds the seizure discharges is characterized by a significantly slower frequency. Thus, the action of nicotine on hippocampal electrical activity is greatly depressed in hypothyroid rabbits.Doses of pentetrazol producing preconvulsive changes and seizure discharges in cortical electrical activity are identical in normal and hypothyroid animals.Therefore, the central actions of various drugs may be influenced to a quantitatively very different extent by hypothyroidism.

Ein Teil der hier beschriebenen Versuche wurde bereits auf der 8. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft in Mainz vorgetragen.     

Effect of anticonvulsants on seizures developing in the course of daily administration of pentetrazol to rats

Progressive behavioral and electroencephalographic (EEG) changes were examined following daily administration of pentetrazol (PTZ) to rats. A dose (40 mg/kg/day i.p.) of PTZ which, on the first day, induced clonic convulsions with spike and wave complexes, over several days progressively increased its effect and finally induced ‘violent convulsions’ with EEG seizures of high frequency components. In rats showing these violent convulsions, the PTZ convulsive threshold was decreased and, even after a 4- to 10-month resting period, the violent convulsion was elicited with the same dose of PTZ. Trimethadione and phenobarbital in doses blocking clonic convulsion in normal rats, did not suppress these violent convulsions. Higher doses of the two drugs were necessary to suppress the violent convulsion. Diphenylhydantoin did not suppress either type of convulsions. It is suggested that the progressive development of seizure by PTZ is a kindling effect and that a part of the neuronal mechanisms by which the violent convulsion occurs is involved in the mechanisms underlying the clonic convulsion.     

灵芝孢子粉对戊四氮致痫大鼠脑组织GDNF与NT-3表达的影响

目的:观察和探讨灵芝孢子粉干预后戊四氮(PTZ)致痫大鼠皮质和海马区胶质细胞源性神经营养因子(GDNF)和神经营养因子-3(NT-3)的变化,进一步研究癫痫的发病机制及灵芝孢子粉的作用机制。方法:Wistar大鼠30只,随机分为正常对照组、癫痫模型组和灵芝孢子粉治疗组,每组10只。模型组和治疗组采用PTZ腹腔注射制作Wistar大鼠慢性点燃模型。实验后断头迅速取脑,采用免疫组化方法检测皮质和海马区GDNF和NT-3表达的变化;同时用Westernblotting检测海马各指标蛋白的变化。结果:灵芝孢子粉干预后,免疫组化显示:皮质和海马区GDNF和NT-3较癫痫模型组明显增加;Western blotting检测显示:海马中GDNF和NT-3表达较癫痫组显著增加。结论:灵芝孢子粉能够增强GDNF和NT-3的表达从而减轻癫痫发作给神经系统带来的损伤,所以灵芝孢子粉可能具有减轻痫性发作、保护神经元的作用。     

Effects of some antiepileptic drugs in pentetrazol-induced convulsions in mice lesioned with kainic acid

Mice were injected with intracerebroventricular (i.c.v.) kainic acid (KA; 0.1 micrograms per animal) and the pentetrazol test was carried out on the fifth day after the administration of the amino acid. The following antiepileptic drugs were tested for anticonvulsant activity in mice lesioned with KA: diazepam (0.4 mg/kg), phenobarbital (12.5 and 25 mg/kg), trimethadione (200 and 400 mg/kg), depakine (200 and 400 mg/kg), carbamazepine (10 and 20 mg/kg), lefadol (bromophenylsuccinimide; 20 mg/kg), and acetazolamide (320 mg/kg). All drugs were given intraperitoneally, except for carbamazepine, which was also given orally in doses of 100 and 200 mg/kg. Pentetrazol was administered subcutaneously in a dose of 110 mg/kg, and the animals were subsequently observed for the occurrence of clonic and tonic convulsions within 30 min. The protective effects of diazepam and phenobarbital were significantly reduced in the KA-lesioned animals, while the actions of the remaining anticonvulsants were unaltered. Moreover, a substantial loss of pyramidal cells in the CA 3 field of the hippocampus was noted after i.c.v. injection of KA. It may therefore be concluded that the mechanism of the action of diazepam and phenobarbital are partially dependent on the intact functions of the hippocampal formation.     

Effects of diazepam on dorsal root potentials induced by cortical paroxysmal activity

The effects of diazepam (DZ), 0.5–1 mg/kg, i.v., on inhibitory presynaptic mechanisms induced at the spinal level by the appearance of cortical seizures produced by pentetrazol have been studied in intact cats anaesthetized with pentobarbital. Spontaneous dorsal root potentials (DRP), induced by isolated discharges and by paroxysmal cortical seizures, were abolished by DZ. After the paroxysmal activity, heterosensory and heterosegmental DRP's, due to cortical hyperexcitability, were suppressed by DZ. In contrast, the segmental DRP which was reduced by pentetrazol, was increased by DZ. These data suggest that: (1) DZ exerts a direct action at the spinal level by increasing segmental presynaptic inhibition as previously described by others. (2) DZ decreases or suppresses presynaptic controls of supraspinal origin by its depressive action on supraspinal structures involved in these phenomena.     

Effects of phenytoin on sympathetic reflex responses in the cat

Phenytoin (DPH), in a low dose (2 mg/kg) was found to potentiate reflex elevations in blood pressure and responses of the nictitating membrane induced either by the electrical stimulation of the sciatic nerve or by intravenously applied pentetrazol in lightly anaesthetized cats. Pressor responses to carotid occlusion under chloralose anaesthesia were also potentiated. In contrast a high dose (20 mg/kg) of DPH exerted an inhibitory effect on these responses. These effects of DPH on sympathetic reflex responses proved to be long-lasting. Intravenously applied picrotoxin (0.05 mg/kg) or the same dose of ouabain, injected into the vertebral artery. partially reversed the inhibitory effect of DPH (20 mg/kg). Our data support the suggestion that DPH exerts its inhibitory action by affecting ionic fluxes in the CNS, mostly in inhibitory structures.