[Hypoxic preconditioning modifies the activity of pro- and antioxidant systems in rat hippocampus].

The effects of repetitive mild hypobaric hypoxic preconditioning upon pro- and antioxidant systems in rat hippocampus were studied. It was found that three-trial preconditioning by mild hypobaric hypoxia (360 mm Hg, 2 h) induced moderate oxidative stress immediately after the last preconditioning trial. In addition, it down-regualted the levels of peptide antioxidants (Trx-1, Trx-2, Cu,Zn-SOD) and several lipid peroxidation products 24 h later.

[Effects of the prenatal hypoxia on the hypothalamic-pituitary-adrenal axis function and working memory in rats].

A comparative analysis of the effects of severe hypobaric hypoxia in different prenatal periods on expression profiles of glucocorticoid receptors (GR) in dorsal (CA1) and ventral (dental gyrus) hippocampus and neocortex of rats, their stress reactivity and working memory has been performed in the present study for the first time. According to the data obtained, severe hypoxia in the prenatal period induces remarkable disturbances of GR expression in the neurons of neocortex of adult males but not females, that correlates to the disruption of working memory in adult males exposed to hypoxia on the prenatal 14-16th days. Elevation of stress plasma corticosterone levels have been observed only in the females subjected to hypoxia on the prenatal 17-19th days.

[Changes in Mn-superoxide dismutase expression in rat hippocampus induced by single and triple exposure to moderate hypobaric hypoxia].

The purpose of this work was to study the dynamics of expression of mitochondrial Mn-dependent superoxide dismutase (Mn-SOD) 3 and 24 hours after single and triple exposure to mild hypoxia. The investigation was conducted in 18 male Wistar rats using immunocytochemical method. It was shown that in various hippocampal areas the effects of single and triple hypoxia exposure on the Mn-SOD expression could be different or largely similar.

[Comparison of effects of a single and thrice-repeated moderate hypobaric hypoxia upon expression of thioredoxine-1 in the rat hippocampus].

We have previously shown that severe acute hypobaric hypoxia (SH) increases the expression of several endogenous antioxidants including thioredoxin-1 (Trx-1) in hippocampal neurons of rats. Preconditioning by three sessions of mild hypobaric hypoxia (MH) significantly augments this increase at the early period after subsequent SH, but MH itself without subsequent SH, in contrast, decreases expression of Trx-1. The dynamics of Trx-1 expression between the first and the last (third) sessions of preconditioning remains, however, unclear.

[Dynamics of lipid peroxidation of membranes in cells and mitochondrial fraction of neocortex in non- and preconditioned rats after severe hypobaric hypoxia].

There was studied effect of severe hypobaric hypoxia and subsequent reoxygenation on level and dynamics of lipid peroxidation in membranes of neocortex cells and in mitochondria-enriched neocortex fraction of non-preconditioned rats and of rats preconditioned thrice with a moderate hypobaric hypoxia. The threefold hypoxic preconditioning increasing brain resistance has been shown to significantly prevent disturbance of lipid peroxidation processes in neocortex--one of the most hypoxia-sensitive brain structures--and to modify development of these processes in mitochondria.

[Effect of prenatal hypobaric hypoxia on activity of the rat brain phosphoinositide system].

Activity of the phosphoinositide system of the intracellular signalization was studied in offspring of rats exposed to severe hypobaric hypoxia at the 14-16th (group 1) or the 18-20th day (group 2) of prenatal development. At the age of 15 days, in animals of both experimental groups the basal level of triphosphoinositides in the brain cortex was shown to be elevated as compared with control. In the group 1 this parameters also remains elevated in adult animals.

[Effect of mild hypobaric hypoxia in the preconditioning regime on expression of pCREB and NF-kappaB transcription factors in the rat hippocampus before and after severe hypoxia].

Preconditioning using threefold mild hypobaric hypoxia (HH) is known to increase the tolerance of vulnerable brain neurons to severe hypoxia and other damaging factors. In the present study, the changes of the expression of transcription factors NF-kappaB (nuclear factor kappa B) and CREB (cAMP response element binding protein) were studied in the hippocampus of rats preconditioned by mild hypoxia. Using immunocytochemical method, it was demonstrated that HH increased NF-kappaB and phosphorylated CREB (pCREB) immunoreactivity in CA1-CA4 fields of the hippocampus and gyrus dentatus.

[Thioredoxin-1 expression level in hippocampal neurons of rats exposed to hypobaric hypoxia].

It was shown recently that preconditioning by 3-time repetitive mild hypoxia significantly augmented expression of thioredoxin-1 (Trx-1) antioxidant protein at 3 h after subsequent acute severe hypoxia in rat hippocampus as compared to the expression of this protein in non-preconditioned rats. However, it was unclear whether this augmentation was due to an accumulation of Trx-1 during the preconditioning before severe hypoxia or by a modification of reaction to severe hypoxia itself. To answer this question, Trx-1 expression level after preconditioning without subsequent severe hypoxia was studied in an experiment on 12 mature male Wistar rats.

[The anxyolytic effect of mild hypobaric hypoxia in a model of post-traumatic stress disorder in rats].

The impact of mild hypobaric hypoxia on the development of anxiety-like state in rats in experimentally simulated human post-traumatic stress disorder was studied. Three-trial exposure to mild hypobaric hypoxia (360 mm Hg for 2 hours daily, for 3 days) in preconditioning or post-conditioning mode performed, respectively, before or after exposure to severe traumatic stress in the "stress-restress" model produced a significant anxiolytic effect on the rat open-field and plus-maze behavior. Anxiolytic effect of modem antidepressant Paxil (20 mg/kg daily, for 3 days) was weaker.

Maternal para-chlorophenylalanine exposure modifies central monoamines and behaviors in the adult offspring.

We reported a perspective animal model of neurodevelopmental disorders using rats prenatally exposed to an inhibitor of serotonin (5HT) synthesis, para-chlorophenylalanine (PCPA). Earlier, we demonstrated that prenatal exposure to PCPA caused fetal 5HT depletion and changes both in open field activity and in depression-related behavior, as well as impairments in spatial learning in the adult offspring (Vataeva et al., 2007).

[Effect of serotonin deficit at different stages of prenatal ontogenesis on behavior of adult male and female rats].

Effects of maternal parachlorophenilalanine (PCPA) administration on the offspring behavior were studied in the open field, Porsolt forced swimming, and Morris water maze tests. PCPA was administered in two different gestational periods: on gestational days (GD) 8-11 or GD 14-17, at doses 200/100/100/50 mg/kg. It was found that prenatal exposure to PCPA results in fetal serotonin (5-HT) depletion and changes in both open field activity and depression-related behavior, as well as impairments in spatial learning in the adult offspring.

[The feasible applications of hypoxic preconditioning for prevention of post-stress depressive episodes].

The protective effect of hypoxic preconditioning on the development of depressive states in rat experimental models has been studied. Three-trial preconditioning by repetitive hypobaric hypoxia (360 mm Hg, 2h) prevented triggering of behavioral depression, pituitary-adrenal axis hyperactivity and impairment of negative feedback in dexamethasone test in rats following inescapable aversive stress in the model of endogenous depression. Anxyolytic and antidepressant-like effect of the hypoxic preconditioning was not less than that of tetracyclic antidepressant ludiomil.

Behavioral alteration in the adult rats prenatally exposed to para-chlorophenylalanine.

In the present work, effects of maternal administration of para-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor, on behavior of adult offspring were studied. Pregnant rats were injected intraperitoneally with PCPA (200/100/100/50 mg/kg) either on the gestational days (GD) 8-11 or 14-17, or with vehicle at the same days. Behavioral parameters, in an open field, the Porsolt forced swim test and the Morris water maze test were evaluated at the age of 3-3.

[The effect of preceding mild hypoxia on the alteration of acquisition and retention of the conditioned passive avoidance behavior caused by severe hypobaric hypoxia in rats].

The purpose of this study was to determine whether mild hypobaric hypoxic preconditioning provides protection against learning deficit caused by subsequent more severe hypoxia insult. Learning was examined using a passive avoidance task. Three groups of Wistar male rats: the intact and exposed to either severe hypoxia (160 Torr, exposition 3 h) or mild hypobaric hypoxic preconditioning (360 Torr, exposition 2 h, repeated three or six times daily) followed by severe hypoxia, were included in this study.

[Early genes expression, structural neuron changes in hypobaric hypoxia and correcting effect of preconditioning].

The effects of severe hypobaric hypoxia and preconditioned severe hypoxia on the expression of early genes products--proteins c-Fos and NGFI-A, and structural changes in rat hippocampal and neocortical neurons were studied using Nissl staining and immunocytochemistry. Severe hypoxia was found to induce a suppression of c-Fos and NGFI-A synthesis (at 3-24 h after exposure) and delayed (by day 3-7) destructive neuronal changes, which developed according to "light" and predominantly "dark" type, that obviously reflected necrotic or apoptotic processes, respectively. The preconditioning in the regime applied abolished these pathological changes, as expressed by stimulation of early gene products expression and marked reduction of neuronal damage following severe hypoxia.

[Adaptive effects of hypoxic preconditioning in brain neurons].

A preventive short-term hypoxia (preconditioning) increases neuronal resistance against subsequent strong hypoxic effects. Literature review and authors' own data on molecular-cellular mechanisms of the hypoxic preconditioning, are presented. Participation of intracellular signal transduction, genome, stress-proteins, and neuromodulating peptides in this process, is discussed.

[Involvement of glutamate receptors (NMDA type) in reaction of brain neurons to anoxia of different duration].

The participation of NMDA receptors in the changes caused by evoked EPSPs in the activity of calcium and phophoinositide intracellular regulatory systems (ICRS) bioelectric activity (evoked EPSPs) and in cell production of polypeptides was studied in rat olfactory cortical slices exposed to short-term anoxia (STA) and long-term anoxia (LTA). To determine NMDA receptor involvement in these functional and metabolic reactions, the slices were treated with the antagonists APV and MK-801 during anoxia of different duration (STA and LTA being 2 and 10 min, respectively) and subsequent reoxygenation. EPSPs were recorded extracellularly in response to lateral olfactory tract stimulation.

[Involvement of the intracellular regulatory systems in the adaptive effect of short-term anoxia in vitro].

Moderate long-term activation of intracellular regulatory system (IRS) was found to be manifested as an increase in the bound calcium content and intensity of the phosphoinositide metabolism following a 30-minute re-oxygenation in the rat olfactory cortex perfused slices. The perfusate induced a similar activation in intact slices-recipients. Long-term anoxia induced a biphasic NMDA-dependent increase in intracellular free Ca2+ and pathogenic hyperactivity of the IRS.

[The intracellular mechanisms of glutaminergic and cholinergic signal transduction in the cerebral cortex].

Stimulation of glytamate- and cholinoreceptors by the agonists induced a prolonged calcium and phosphoinositide responses to short-term anoxia or administration of an antioxidant agent in cortical structures. Processes of adaptation essentially modified these responses.

[The molecular cellular mechanisms of the protective effect of short-term anoxia].

Recovery of unit activity was studied after a 5-min anoxia following a short-term anoxia in the cat brain cortex. The short-term anoxia's protective effect was only revealed in case when it had induced the phenomenon of asphyxic hyperactivity. The protective effect seems to be due to the short-term anoxia-induced changes in the calcium, polyphosphoinositide and cAMP regulatory systems' activity.

[The effect of short-term anoxia on the mechanisms of intracellular signal transduction in the cat cerebral cortex].

Changes in the intracellular bound calcium, polyphosphoinositides and cAMP were studied during 60 min. of recovery after 50-90 s of anoxia in the cat cerebral cortex. Different changes of the intracellular regulatory system's components were revealed in the reoxygenation period.

[The participation of intracellular regulatory systems in the reactions of the cat cerebral cortical neurons to fosfakol].

The effects of paraoxon (1.5-4.5 LD50) on the levels of intracellular regulatory components, such as membrane-bound calcium (Ca(b)) and polyphosphoinositides (PPI) were studied along with microcirculation and neuronal bioelectric activity control in the feline cerebral cortex.

[Changes in the content of rat brain polyphosphoinositides after exposure to high partial pressures of helium and nitrogen].

Effect of the medium with high partial pressure of helium and nitrogen on the content of di- and triphosphinositides in the rat brain great hemispheres. The stay of the rats in helium-oxygen mixture under the pressure of 40 kg/cm2 for 1 h is accompanied by the true decrease in the content of the both components of polyphosphoinositides whose value does not depend on the decompression conditions. Nitrogen-oxygen mixture under the pressure of 15 and 25 kgf/cm2 also evokes a decrease of the content of di- and triphosphoinositides.

[The involvement of intracellular regulatory systems in the mechanisms of the recovery of the neuronal activity of the cerebral cortex in anoxia].

Changes in the membrane-bound calcium (Ca(b)), polyphosphoinositides (PPI) and cAMP, as well as unit spike activity of the cat brain cortex were studied during 30 min of recovery after 5-min anoxia. The cats with poor recovery revealed low Ca(b) and PPI but high level of the cAMP content. The group of cats with more successful restitution after anoxia revealed a sharp increase in the Ca(b) and PPI and not in the cAMP.