Memantine attenuates cognitive impairments after status epilepticus induced in a lithium-pilocarpine model.

The capability of memantine, a noncompetitive antagonist of the NMDA receptors, to prevent impairments of cognitive functions in rats was investigated in the lithium-pilocarpine model of epilepsy. After status epilepticus, rats exhibited impaired exploratory behavior and spatial memory, and a decline of extinction of orienting behavior. Memantine administration prevented these disturbances. Thus, the blockade of the NMDA receptors immediately after status epilepticus allowed prevention of the development of the possible cognitive impairments.

Impairment of exploratory behavior and spatial memory in adolescent rats in lithium-pilocarpine model of temporal lobe epilepsy.

Cognitive impairment in six-week -old rats has been studied in the lithium-pilocarpine model of adolescent temporal lobe epilepsy in humans. The pilocarpine-treated rats (n =21) exhibited (a) a decreased exploratory activity in comparison with control rats (n = 20) in the open field (OP) test and (b) a slower extinction of exploratory behavior in repeated OP tests. The Morris Water Maze (MWM) test showed that the effect of training was less pronounced in the pilocarpine-treated rats, which demonstrated disruption of predominantly short-term memory. Therefore, our study has shown that lithium-pilocarpine seizures induce substantial changes in exploratory behavior and spatial memory in adolescent rats. OP and MWM tests can be used in the search of drugs reducing cognitive impairments associated with temporal lobe epilepsy.

[THE EFFECTS OF CHRO- NIC ADMINISTRATION OF MODERATE DOSE OF PROINFLAMMATORY CYTOKINE INTERLEUKIN-1ß ON RAT INVESTIGATIVE BEHAVIOR AND SPATIAL MEMORY].

The aim of this study was to discover the effects of chronic intraperitoneal administration of proinflammatory cytokine interleukin-1ß (IL-1ß) on rat investigative behavior and spatial memory. Rats were injected with a moderate pyrogenic dose of IL-1ß (0.5 mkg/kg) daily during 14 days (7 days before tests and 7 testing days). The behavior was examined in 23.5 hours after the previous injection of cytokine. The test battery included: "The open field" (within 3 consecutive days), "The exploration of novel objects", and "The Morris water maze". The animals treated with IL-1ß differed from the control animals in an essential decrease of locomotor activity, slight increase of anxiety and suppression of exploratory behavior. The impairment of spatial memory was not revealed.

[Impairments of conditioned behavior in adult rats induced by interleukine-1beta treatment in early postnatal ontogenesis].

Impairments of cognitive functions in children and adolescents are often consequences ofperinatal pathology (natal injuries, ischemia, hypoxia, infection and allergic diseases), which are accompanied by enhanced production ofproinflammatory cytokine interleukine-1beta. In this work it was shown that treatment with interleukine-1beta during the third week of life impaired active and passive avoidance conditioning in adult rats at the age of 60-70 days.

[Morphofunctional features of microtubule ultrastructure and MAP2 protein phosphorylation in hippocampal neurons of rats with predisposition to audiogenic epilepsy]. / Morfofunktsional'nye osobennosti ul'trastruktury mikrotrubochek i fosforilirovaniia belka MAP2 v neironakh gippokampa krys, predraspolozhennykh k audiogennoi épilepsii.

It has been shown that modification of microtubule (MT) ultrastructure are accompanied by functional changes in microtubule-associated protein MAP2 in the hippocampus of Krushinsky--Molodkina rats (KM), which are prone to autogenic seizures. The morphogenetic analysis revealed that contrary to Wistar rats, which are insensitive to sound stimulation, in KM the middle length of microtubule fragments in the apical dendrites of pyramidal neurons in CA3 hippocampal area was reduced. Using immunoblot and autoradiography methods, we found that the level of MAP2 and the rate of its cAMP = and Ca(2+)-calmodulin-dependent phosphorylation were increased in hippocampus of KM, in comparison with Wistar rats. Daily repeated sound stimulation for 20 days (audiogenic kindling) induced a further decrease in length of MT fragments, and an increase of their density in the proximal part of apical dendrites of KM. Moreover, audiogenic kindling induced additional increase in MAP2 phosphorylation state, but did not change the level of MAP2 in KM hippocampus. We suppose that the obtained alteration of MAP2 phosphorylation state exerted influence on kinetic parameters of microtubule assembly, serving as part of genetically determined predisposition of KM to audiogenic epilepsy.

Increases in the threshold for the development of epileptiform activity in field CA1 of Krushinskii-Molodnika rat hippocampal slices as an adaptive protective mechanism.

Studies were carried out into the chances of developing epileptiform activity in the neuronal network of hippocampal field CA1 in normal (Wistar) rats and in rats genetically predisposed to audiogenic convulsions (Krushinskii-Molodkina rats). The development of epileptiform activity was assessed in terms of the reduction in the threshold for development trains of epileptiform discharges in field CA1 of hippocampal slices, which were induced using episodic increases in the extracellular K+ concentration ([K+]0) or decreases in the extracellular Mg2+ concentration ([Mg2+]0). These experiments showed that the threshold for the development of trains of epileptiform discharges increased in field CA1 of hippocampal slices of Krushinskii-Molodkina rats, while the excitability of glutamatergic Schaffer collaterals/commissural fibers was decreased. In addition, Krushinskii-Molodkina rats showed no long-term potentiation of glutamatergic synaptic transmission or potentiation of the EPSP-spike system in pyramidal neurons, induced in field CA1 of hippocampal slices in Wistar rats by reductions in [Mg2+]0 and increases in [K+]0 respectively. It is suggested that this underlies the operation of an adaptive protective mechanism preventing the propagation of convulsive activity in the Krushinskii-Molodkina rat brain.

Kindling-like state occurring on periodic increases in the extracellular K+ concentration in field CA1 in rat hippocampal slices.

Transient periodic increases in the extracellular K+ concentration (20 mM, 30 sec, 3-6 episodes) led to the appearance of a kindling-like state in local neuronal networks of field CA1 of rat hippocampal slices. A criterion for the appearance of this state was a reduction in the threshold for the generation of multiple population discharges and an increase in the total number of population spikes within discharges (epileptiform activity). This state correlated with potentiation of excitatory postsynaptic potentials (EPSP) (long-term increases in pyramidal neuron excitability), but not with potentiation of glutamatergic synaptic transmission in field CA1 of hippocampal slices. The role of the various Ca2+ channels in inducing and maintaining the kindling-like state in rat hippocampal sections, evoked by periodic increases in the extracellular K+ concentration, is discussed.

[Increasing threshold of the epileptiform activity in the CA1 field of hippocampal slices of Krushinskii-Molodkina rats as protective adaptation mechanism]. / Povyshenie poroga razvitiia épileptiformnoi aktivnosti v pole srezov gippokampa krys linii Krushinskogo-Molodkinoi kak adaptivnyi zashchi tnyi mekhanizm.

The Krushinsky-Molodkina rat CA1 hippocampal slices revealed an increased threshold of the epileptiform activity development, a depressed signal transmission in the presynaptic glutamatergic fibres, no long-term increase in excitability of the CA1 pyramidal neurons characteristic of Wistar rats following Mg2+ removal and K+ increase. These events suggest a protective adaptive mechanism preventing propagation of seizure activity into limbic structures of the rats.

[A kindling-like state during a periodic increase in extracellular K+ concentration in the CA1 field of rat hippocampal slices]. / Kindlingpodobnoe sostoianie pri periodicheskom povyshenii vnekletochnoi kontsentratsii K+ v pole CA1 srezov gippokampa krysy.

Short-term repeated increases of extracellular K+ resulted in occurrence of a kindling-like phenomenon in local neuronal network of the CA1 region in hippocampal slices. The phenomenon well correlated with the ES potentiation. The role of various Ca2+ channels in this phenomenon is discussed.

[The effect of antioxidants on functional brain disorders caused by low-intensity ionizing radiation]. / Issledovanie vliianiia antioksidantov na narusheniia funktsional'noi aktivnosti mozga, vyzvannye ioniziruiushchim izlucheniem maloi moshchnosti.

The effects of daily intraperitoneal injections of alpha-tocopherol (30 mg/kg per day) and synthetic antioxidant IHFAN-30 (30 mg/day) in rats were compared during low-level ionizing radiation (10 days, dose rate 5 mGy/h, total dose 1.2 Gy). There were analysed: (1) amplitude of population spike of hippocampal slices; (2) endogenous phosphorylation in vitro of hippocampal synaptic proteins in the presence of cAMP; (3) formation, manifestation and reduction of food-procuring reflex. The findings showed that antioxidants made some correction of the functional state of hippocampal slices and cAMP-dependent phosphorylation system activity in brain cells from irradiated animals. No influence on training and memory functions was detected.