Chronic Effects of Modeled Myocardial Infarction, Thoracic Trauma, and Denervation of Hind Limb on Rheographic Parameters of Rat Femoral Arteries In Situ.

In experiments on narcotized male rats (n=85), the mean electroimpedance Z and peak-to-peak magnitudes (the swing ranges) of passive (ΔZp) and active (ΔZa) pulsatile electroimpedance oscillations of isolated segment of femoral arteries were determined in situ. These rheographic parameters (RP) were measured in intact animals and in those with modeled chronic myocardial infarction, chronic denervation of the right hind leg, as well as in rats subjected to sham operations to mimic denervation or infarction (with thoracic trauma). The rats with modeled myocardial infarction demonstrated decreasing trends of all RP. In sham-operated rats with thoracic trauma, ΔZp increased significantly on postsurgery months 2-4 by 4.3 times in comparison with the control. No essential correlation was found in denervated rats between RP of any femoral artery and severity of neuropathic pain syndrome assessed by autotomy of the operated leg. In these rats, the mean electroimpedance Z of any femoral artery was significantly greater than the control level. They demonstrated especially high values of ΔZp with significant difference between ΔZp of innervated and denervated hind leg. In denervated rats, ΔZa was significantly greater than the control value without significant difference between ΔZa of both femoral arteries. The paradoxically great increase of ΔZp (100- and 50-fold for innervated and denervated legs, respectively) and a significant 3-fold increment of ΔZa in both hind legs provoked by denervation of one of them are discussed in relation to searching for the ways of systemic influences on vascular network in clinics and experiments.

Аnticonvulsant effects of citicoline and diazepam at their combined application on model of the acute generalized convulsions induced by pentylenetetrazole in Wistar rats.

The purpose: Studying of efficiency of the combined application of the citicoline possessing nootropic and anticonvulsive action and antiepileptic drug of diazepam on the acute generalized convulsions (AGC) caused by a convulsant pentylentetrazole (PTZ). Methods: Experiments are executed on the male Wistar rats (n = 68) weighing 160-190 g on the AGС model caused by of PTZ in a dose of 80 mg/kg, intraperitoneally (i.p.). For studying of efficiency of the combined use of drugs determined the minimum anticonvulsive action of a citicoline (Tserakson, «Nicomed Ferrer Internacional, S.A.¼) and diazepam (Relanium, Warsaw pharmaceutical plant of Polf AO, Warsaw, Poland). For this citicoline were administered i.p. in doses 500 and 300 mg/kg 1 hour before the PTZ and diazepam - in doses of 0,5 and 0,25 mg/kg 30 min before administration of PTZ. Control animals were injected with saline to the same extent and under the same experimental conditions. Results: It is shown that the combined administration of a citicoline and diazepam in minimum active doses (300 and 0.25 mg/kg respectively), increases anticonvulsive properties of both drugs. Conclusion: The combined administration of citicoline with diazepam in minimally active doses enhances anticonvulsant properties of both drugs, thereby reducing the risk of development of side effects. In addition, the research may serve as experimental justification for the use of drugs in case of convulsions for the purpose beneficial effect on cognitive function and delays of progressing of neurodegenerative processes.

[Gaba and its Receptors in Pathogenesis of Epilepsy].

This review presents summarizes data on the structural and functional organization of the GABAergic system of the brain, mechanisms of GABAergic transmission, about the characteristics of GABA-receptors and GABAergic inhibition forms. Reviewed issues of involvement of GABA inhibitory neurotransmitter and various types of GABA-receptors in epileptogenesis. The experimental and clinical data testifying to an important role of GABA and its receptors in an epileptogenesis are presented.

Effects of antibodies to glutamate on focal penicillin-induced epileptic activity.

The effects of intranasal pretreatment with antibodies against glutamate on focal penicillin-induced epileptic activity were studied by recording electrocorticogram in non-anesthetized freely moving male Wistar rats. Anticonvulsant effects of intranasal administration of anti-glutamate antibodies (300 µg/kg) 1 h before application of penicillin (30,000 U/ml) on the sensorimotor cortex was demonstrated: the latency of ictal discharges increased and their frequency decreased.

Effect of classic convulsants on Cl- conductance of the GABA(A) receptor complex in membranes of cerebral cortex cells at the early stage of kindling.

Muscimol-stimulated Cl- conductance of synaptoneurosomes from the cerebral cortex of Wistar rats increased during the early stage of pharmacological kindling not inducing the seizure response in animals. Picrotoxin, bicuculline, and pentylenetetrazole potentiated inhibition of muscimol-dependent 36Cl- entry into synaptoneurosomes, which attested to increased sensitivity of the GABA(A) receptor/Cl- ionophore complex to classic convulsants.

Cl(-) conduction of GABAA receptor complex of synaptic membranes in the cortex of rats at the middle stage of chronic cerebral epileptization (pharmacological kindling).

Experiments on Wistar rats showed a decrease in basal and muscimol-stimulated 36Cl(-) entry into synaptoneurosomes isolated from the cerebral cortex during the middle stage of kindling (30 mg/kg pentylenetetrazole intraperitoneally for 14 days) characterized by the development of convulsions of higher (2 points) severity in comparison with the previous stage.

Immunobiological specificity of antibodies against glutamate and gamma-aminobutyric acid.

Experiments on C57Bl/6 mice showed that chronic epileptization of the brain (pharmacological pentylenetetrazole kindling) is accompanied by induction of autoantibodies against glutamate and GABA. Immunohistochemical similarity of antibodies against glutamate and GABA was demonstrated. Study on the model of pentylenetetrazole-induced acute generalized epileptiform activity showed high immunobiological specificity of intraperitoneally injected antibodies against GABA and glutamate: antiepileptic effect of antiglutamate antibodies and proepileptic effect of antibodies against GABA.

Effect of systemic treatment with antibodies against glutamate on the seizure response of C57Bl/6 mice after pentylenetetrazole kindling.

We studied the effect of single intraperitoneal injection of antibodies against glutamate on acute generalized epileptiform activity induced by intravenous injection of pentylenetetrazole in kindled C57Bl/6 mice. We found that in animals at various stages of kindling, administration of antibodies against glutamate in a dose of 25 mg/kg 1.5 h before testing increases the threshold of clonic seizures and tonic phase of seizures with lethal outcome and latency of seizure development, i.e. produces an antiepileptic effect.

Cl- conduction of GABA(A) receptor complex on synaptic membranes in rat cortex at the early stage of chronic cerebral epileptization.

Experiments on Wistar rats showed that muscimol-stimulated Cl(-) conduction of synaptoneurosomes, isolated from the cerebral cortex increased after 5-day systemic treatment with subconvulsive doses of pentylene tetrasole during the initial stage of pharmacological pentylene tetrasole kindling, characterized by gradually augmenting convulsive readiness of the brain. This indicates an increase in functional activity of the GABA(A) receptor/Cl(-) ionophore complex.

Neuroimmunomodulatory effect of antibodies against GABA on acute generalized and chronic epileptiform activity.

We studied the possibility of induction of anti-GABA autoantibodies during chronic epileptization of the brain and the effect of systemic intraperitoneal administration of anti-GABA antibodies to C57Bl/6 mice on acute generalized and chronic epileptiform activity. It was found for the first time that chronic epileptization is accompanied by induction of anti-GABA autoantibody synthesis. Antibodies against GABA produced a proepileptic effect.

Systemic administration of antibodies to glutamate increases seizure threshold for pentylenetetrazole.

We studied the effect of single intraperitoneal treatment with antibodies to glutamate on pentylenetetrazole-induced acute generalized epileptiform activity in C57Bl/6 mice. The antiepileptic effect was observed 1.5 and 24 h after administration of antibodies to glutamate in doses of 10, 25, and 50 mg/kg. This treatment increased the thresholds of clonic seizures and tonic phase of seizures with lethal outcome.

Elevation of corazol-induced seizure threshold after active immunization of mice of various genetic strains with glutamate-bovine serum albumin conjugate.

We studied the effect of active immunization with glutamate-bovine serum albumin conjugate on acute generalized epileptiform activity evoked by single administration of corazol. Antibodies to glutamate produced an antiepileptic effect and elevated the threshold for clonic seizures and tonic phase of lethal seizures. In BALB/c mice this effect was more pronounced than in C57BL/6 mice.

Contribution of protein synthesis to mechanisms of antiepileptic system activity in kindling.

We studied changes in protein composition and their effects on convulsive activity in drug-induced and electrical kindling. Injection of protein fraction of brain extract from animals subjected to metronidazole-induced kindling to intact recipients reduced their sensitivity to the convulsant (i. e. increased the dose of metronidazole inducing clonic convulsions and lethal seizures). Incorporation of labeled amino acids in proteins in different brain structures after appearance of stable afterdischarges in the zone of synaptic stimulation significantly decrease compared to the control. Label incorporation decreased also in the frontal and occipital cortex. Kindling-associated changes in the protein spectrum were studied by electrophoresis.