State of the antioxidant system during corazole kindling in rats

Antioxidation system was investigated in rats during kindling formation caused by daily administration of corazole in under-threshold doses. No changes have been observed in the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase and alpha-tocopherol content in the rat brain and blood. It is suggested that corazole-induced predisposition to epileptic activity is formed by mechanisms which are not associated with lipid metabolism in nervous tissue.     

杏仁核点燃模型癫痫样放电传播途径研究

目的 :探讨杏仁核点燃模型癫痫样放电的传播途径。方法 :选择健康Wistar大鼠 3 0只以电刺激杏仁核的方式制作杏仁核点燃癫痫模型 ,于右侧杏仁核、左侧海马及右侧额叶皮质埋植电极记录脑电活动 ,观察电刺激杏仁核时在杏仁核、海马及额叶皮质出现癫痫样放电的潜伏期、最低刺激强度及癫痫样放电的持续时间。结果 :杏仁核出现癫痫样放电时 ,海马及皮质均未记录到癫痫样放电。而当杏仁核、海马及皮质三处出现癫痫样放电时的最低刺激强度依次增大 ,潜伏期依次延长 ,海马处癫痫样放电的持续时间最长。结论 :杏仁核点燃模型癫痫样放电可能由杏仁核经海马传至皮层 ,海马可能为癫痫样放电传播的重要结构     

The effect of the cerebrospinal fluid from rats subjected to picrotoxin-induced kindling on the motor activity and seizure susceptibility of recipient animals

Experiments on rats have shown that repeated administration of primarily subthreshold dose of picrotoxin leads to the occurrence and progressive enhancement of seizure manifestations. During picrotoxin kindling the decrease of locomotor activity in interictal periods was recorded. Microinjection of cerebrospinal fluid (CSF) of kindled rats into lateral brain ventriculi of recipients resulted in decrease of locomotor activity and acute primarily generalized picrotoxin induced seizures. These effects of CSF were blocked by naloxone administration and were observed only if injecting CSF which was preliminarily treated with protease inhibitors. It is concluded that endogenous opioid substances accumulate in CNS during kindling and evoke a decrease in the locomotor activity. These substances act as anticonvulsant factors which control the development of epileptic activity.     

Amygdaloid kindling in alloxan-diabetic rats

Wistar rats, made diabetic by intravenous administration of alloxan, 40 mg/kg, were submitted to amygdala kindling. The EEG and behavioral responses elicited by stimulating the amygdala nuclei in these animals were compared with those observed in control rats. Alloxan-treated rats required more stimulation to kindle, had increased duration of afterdischarges (AD), presented intense interictal spiking, and exhibited greater number of wet-dog shakes than controls. Although the AD threshold was not different between control and experimental rats, the above results seem to indicate an increase in the local epileptic susceptibility represented by longer ADs. On the other hand, this increased local discharge seems to be unable to access the generalization mechanism, which can be verified by the increased kindling rate. Hyperosmolarity, pH alterations, or other generalized metabolic changes frequently associated with diabetes could be implicated in these results.     

Anticonvulsive properties of peptide ACTH4-7 pro-gly-pro detected in amygdaloid kindling and audiogenic epilepsy in rats

Effects of the ACTH4-7 pro-gly-pro, calcium valproate ("Germed", DDR) and nembutal on kindling preparation and audiogenic epilepsy were investigated. Development of after-discharges in response to repeated amygdaloid electrical stimulation was assessed in normal rats and in rats susceptible to audiogenic epilepsy (KM line of rats). ACTH4-7 pro-gly-pro had an anticonvulsant profile. ACTH4-7 pro-gly-pro decreased seizure threshold in the audiogenic epilepsy test, but did not prevent the motor convulsions.     

Role of the substantia nigra in antiaggressive and anticonvulsant effects of diazepam during pharmacological kindling

Having set up pharmacological kindling in rats by repeated injection of picrotoxin at a subthreshold dose i.p., a study was made of activity produced by injecting the trypsinized protein fragment, T5 — diazepam binding inhibitor (DBI) in man at a dose of 10 µg — into the reticular section of the substantia nigra (SN). Severity of convulsive effects increased in animals under the influence of DBI and the anticonvulsant action of diazepam declined. Intranigral injection of DBI did not affect the threshold triggering attacking behavior in rats when current was passed through the electrically-conducting floor, nor did the antiaggressive action of diazepam change under these conditions. Findings would indicate that the benzodiazepine receptors of the SN contribute to suppression of epileptic response during kindling and to the production of anticonvulsive (but not antiaggressive) diazepam action.N. I. Pirogov Medical Institute, Odessa. Translated from Neirofiziologiya, Vol. 22, No. 4, pp. 482–485, July–August, 1990.     

The role of the opiate mechanisms of the hippocampus and substantia nigra in the behavioral and convulsive disorders in picrotoxin-induced kindling]

It was shown in the experiments on rats that the repeated picrotoxin administration resulted in the kindling of generalized seizures. Generalized convulsions were followed by the development of either postictal depression or explosiveness. The injection of mu-opiate agonist met-enkephalin into hippocampus of kindled rats resulted in the increase in the severity of seizure reactions which were induced by picrotoxin and also in the increase in the number of animals with postictal explosiveness. The injection of dynorphin-A-1-13 (kappa-opiate agonist) into substantia nigra reticulata induced the locomotor depression which was like one in postictal period and resulted in the decrease of picrotoxin-induced seizures severity. It was concluded that mu-opiate system of hippocampus took part in the formation of generator of pathologically enhanced excitation in the structure during kindling and the development of seizure syndrome, providing also the postictal explosiveness. Kappa-opiate system of substantia nigra plays an important role in the activation of the antiepileptic system, limitation of seizures and the development of postictal depression.     

Role of lipid peroxidation in damage to serotonin receptors and development of epileptiform seizures during hyperoxia

Hyperoxia brought about substantial accumulation of primary and end products of lipid peroxidation (LPO) and a significant lowering of alpha-tocopherol content in rat brain tissues. Preinjection of animals with synthetic and natural antioxidants (4-methyl-2,6-ditretbutylphenol and alpha-tocopherol) prevented LPO activation and decreased the frequency of epileptiform seizures induced by hyperoxia. Administration of a mixture of unsaturated fatty acids led to an opposite effect. The changes in the properties of serotonin receptors were found to be dependent on the hyperoxia-induced LPO. These changes were marked by the reduced specific binding of serotonin with neuronal membranes of the rat brain cortex. The data obtained allowed the conclusion about the key role played by LPO activation in toxic action of hyperbaric activation on the brain.     

Wet-dog shaking behavior in rats in hippocampal kindling

The kindling phenomenon, induced by repetitive electrical stimulation of the hippocampus of the rat is associated with the production of a particular behavior: the Wet Dog Shakes (WDS). The evolution of WDS is strongly and negatively correlated with the intensification of motor seizures. Some differences can be seen in the occurrence of WDS according to whether the stimulation is applied in dorsal or in ventral hippocampus. Although the anatomical substrate responsible for this behavior is not clearly defined, the relationship between WDS and kindling let us consider it as an index of the generalization of the epilepsy.     

Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis.

Kindling, induced by repeated subconvulsive electrical or chemical stimulations leads to progressive and permanent amplification of seizure activity, culminating in generalized seizures. We report that kindling induced by electrical stimulation in the ventral hippocampus leads to a marked and transient increase in mRNA for NGF and BDNF in the dentate gyrus, the parietal cortex, and the piriform cortex. BDNF mRNA increased also in the pyramidal layer of hippocampus and in the amygdaloid complex. No change was seen in the level of HDNF/NT-3 mRNA. The increased expression of NGF and BDNF mRNAs was not influenced by pretreatment with the NMDA receptor antagonist MK801, but was partially blocked by the quisqualate, AMPA receptor antagonist NBQX. The presumed subsequent increase of the trophic factors themselves may be important for kindling-associated plasticity in specific neuronal systems in the hippocampus, which could promote hyperexcitability and contribute to the development of epileptic syndromes.     

Involvement of nitric oxide in pentylenetetrazole-induced kindling in rats

We investigated the role of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) in the pentylenetetrazole (PTZ)-induced kindling in rats. Seizures were induced by single administration of PTZ, which was associated with an increase in levels of NO metabolites (NOx) in the hippocampus. Pretreatment with a neuronal NO synthase inhibitor, 7-nitroindazole (7-NI), diminished the PTZ-induced increase in NOx levels without affecting the seizure intensity. Repeated administration of PTZ produced a gradual increase in the seizure intensity, leading to the development of kindling. In the kindled rats, PTZ at a dose of 40 mg/kg increased NOx levels in the hippocampus, whereas it had no effect in control animals. Cotreatment of 7-NI with PTZ blocked the development of kindling and attenuated the PTZ-induced increase in NOx levels. A significant increase in BDNF levels was observed in the hippocampus of the kindled rats, which returned to the control levels following seizures induced by PTZ. 7-NI reduced the hippocampal BDNF levels in control rats and suppressed the increase of BDNF levels in the kindled rats. Our findings suggest that NO plays a role in the development of PTZ-induced kindling and that BDNF may contribute to the NO-dependent plastic changes in neuronal excitability.     

Intracerebral beta-endorphin, met-enkephalin and morphine: kindling of seizures and handling-induced potentiation of epileptiform effects

The effects of repeated infusion of small, initially subconvulsive amounts of beta-endorphin, met-enkephalin or morphine sulfate into the amygdala and hippocampus were investigated. beta-endorphin and met-enkephalin evoked epileptiform spiking when infused into the posterior amygdala or ventral hippocampus. Morphine evoked epileptiform spiking when infused into the anterior amygdala. Naloxone blocked or terminated the spiking. Repetition of the infusions led to the gradual development of bilateral generalized convulsions by beta-endorphin and met-enkephalin and to the development of tolerance to morphine. An unexpected observation was that handling, immobilization or conspecific threat potentiated the epileptiform effects of beta-endorphin and morphine in many cases. These results suggest that endogenous opiate mechanisms might play a role in convulsive seizures and that stressful stimuli can exacerbate opiate seizures.     

Rhythmic oscillations in amygdala excitability during kindling

Unilateral amygdala electrodes were implanted in male Sprague-Dawley rats stimulated once daily with a 200 μamp pulse of 500 millisecond duration to produce kindling. Forty-six percent (12 of 26) of the animals that eventually developed after-discharges demonstrated rhythmic oscillations in after-discharge duration. The presence or absence of generalized bilateral clonic seizures also showed rhythmic oscillations in close association with after-discharge duration. It is suggested that during kindling some animals, independent of electrode placement, develop rhythmic oscillations in excitability of the amygdala. This model may represent a means of experimentally eliciting or uncovering neuronal substrates which show regular alterations in excitability and may be relevant to the oscillations in mood and behavior observed in the affective disorders.     

Role of calcitonin gene-related peptide in the phenol-induced neurogenic hypertension in rats

Previous investigations have demonstrated that capsaicin-sensitive sensory nerves are involved in the development of hypertension in some rat models of hypertension. To determine the role played by calcitonin gene-related peptide (CGRP; the predominant neurotransmitter in capsaicin-sensitive sensory nerves) in a rat model of neurogenic hypertension, in which hypertension was induced by injecting 50 microl of 10% phenol in the lower pole of the left kidney, systolic blood pressure (SBP) was monitored by the tail-cuff method throughout the experiment. Fifteen days after injection of phenol, mean arterial pressure (MAP), concentrations of CGRP in the plasma, the expression of CGRP mRNA in dorsal root ganglia (DRG) and CGRP content in laminae I and II of the spinal cord were measured. SBP was significantly increased 5 days after the intrarenal injection of phenol (164+/-7 mm Hg, p<0.01). At the end of experiment, blood pressure (BP) was significantly elevated in the phenol-injected rats compared with the controls (SBP: 187+/-6 vs. 122+/-4 mm Hg, p<0.01; MAP: 157.56+/-3.02 vs. 103.80+/-2.04 mm Hg, p<0.01). Treatment with capsaicin, which selectively depletes neurotransmitters from the capsaicin-sensitive nerves, failed to enhance the development of hypertensive responses to the intrarenal injection of phenol. Intravenous administration of CGRP(8-37), the specific CGRP receptor antagonist, also failed to increase the already elevated MAP. The expression of CGRP mRNA (both alpha- and beta-CGRP isoforms), the content of CGRP in laminae I and II of the dorsal horn of the spinal cord and the concentration of CGRP in the plasma was decreased in the rats treated with phenol. These results suggest that CGRP does not play a counterregulatory role in the phenol-induced hypertensive rats, and support the hypothesis that reduction of CGRP (alpha and beta isoforms) could contribute to a blood pressure elevation in this setting.     

Subclinical epileptiform process in patients with unipolar depression and its indirect psychophysiological manifestations

Background

According to recent clinical findings epileptiform activity in temporolimbic structures may cause depressive and other psychiatric symptoms that may occur independently of any seizure in patient''s history. In addition in these patients subclinical seizure-like activity with indirect clinical manifestations likely may occur in a form of various forms of cognitive, affective, memory, sensory, behavioral and somatic symptoms (the so-called complex partial seizure-like symptoms). A typical characteristic of epileptiform changes is increased neural synchrony related to spreading of epileptiform activity between hemispheres even in subclinical conditions i.e. without seizures. These findings suggest a hypothesis that measures reflecting a level of synchronization and information transfer between hemispheres could reflect spreading of epileptiform activity and might be related to complex partial seizure-like symptoms.

Methods and Findings

Suitable data for such analysis may provide various physiological signals reflecting brain laterality, as for example bilateral electrodermal activity (EDA) that is closely related to limbic modulation influences. With this purpose we have performed measurement and analysis of bilateral EDA and compared the results with psychometric measures of complex partial seizure-like symptoms, depression and actually experienced stress in 44 patients with unipolar depression and 35 healthy controls. The results in unipolar depressive patients show that during rest conditions the patients with higher level of complex partial seizure like symptoms (CPSI) display increased level of EDA transinformation (PTI) calculated between left and right EDA records (Spearman correlation between CPSI and PTI is r = 0.43, p = 0.004).

Conclusions

The result may present potentially useful clinical finding suggesting that increased EDA transinformation (PTI) could indirectly indicate increased neural synchrony as a possible indicator of epileptiform activity in unipolar depressive patients treated by serotoninergic antidepresants.     

降钙素基因相关肽在大鼠肝肺综合征发病机制中的作用

目的探讨降钙素基因相关肽(CGRP)在大鼠肝肺综合征(HPS)发病机制中的作用。方法应用放射免疫分析法检测HPS大鼠血浆和肝组织、肺组织匀浆中CGRP的水平。结果(1)HPS大鼠血浆和肝组织、肺组织匀浆中CGRP水平动态升高。(2)各阶段血浆和肝组织、肺组织匀浆中CGRP水平与谷丙转氨酶(ALT)、总胆红素(TBIL)呈正相关。结论在HPS形成过程中,血浆和肝组织、肺组织匀浆中CGRP水平持续升高,与肝功能受损状态和腹水形成有关,提示血管活性物质CGRP可能参与HPS的发生。     

Role of azaamino acid residue in beta-turn formation and stability in designed peptide.

The structural perturbation induced by C(alpha)-->N(alpha) exchange in azaamino acid-containing peptides was predicted by ab initio calculation of the 6-31G* and 3-21G* levels. The global energy-minimum conformations for model compounds, For-azaXaa-NH2 (Xaa=Gly, Ala, Leu) appeared to be the beta-turn motif with a dihedral angle of phi= +/- 90 degrees, psi=0 degrees. This suggests that incorporation of the azaXaa residue into the i+2 position of designed peptides could stabilize the beta-turn structure. The model azaLeu-containing peptide, Boc-Phe-azaLeu-Ala-OMe, which is predicted to adopt a beta-turn conformation was designed and synthesized in order to experimentally elucidate the role of the azaamino acid residue. Its structural preference in organic solvents was investigated using 1H NMR, molecular modelling and IR spectroscopy. The temperature coefficients of amide protons, the characteristic NOE patterns, the restrained molecular dynamics simulation and IR spectroscopy defined the dihedral angles [ (phi i+1, psi i+1) (phi i+2, psi i+2)] of the Phe-azaLeu fragment in the model peptide, Boc-Phe-azaLeu-Ala-OMe, as [(-59 degrees, 127 degrees) (107 degrees, -4 degrees)]. This solution conformation supports a betaII-turn structural preference in azaLeu-containing peptides as predicted by the quantum chemical calculation. Therefore, intercalation of the azaamino acid residue into the i+2 position in synthetic peptides is expected to provide a stable beta-turn formation, and this could be utilized in the design of new peptidomimetics adopting a beta-turn scaffold.     

Role of genetic factors in the formation of trace reactions in man

Trace processes due to presentation of visual nonverbal information, and the dynamics of the bioelectrical parameter (mean level of asymmetry of EEG-waves) were studies in 32 pairs of monozygote and 38 pairs of dizygote twins with twins method. Statistical processing of the data revealed a significant effect of genetic factors on the formation of individual variability of the characteristics of trace processes in humans. The results obtained showed that with increased functional load the intrapair similarity of trace reactions increased in monozygote twins and did not change or decrease in dizygote twins and in unrelated pairs. This fact is interpreted at a dependence of appearance of geneticly determined neurophysiological characteristics on the level of functional activity of the nervous system.