The normal functioning of the vascular system in early ontogenesis can be altered by adverse effects affecting the organism of the fetus / newborn during pregnancy, during or after childbirth. However, at the moment there is not enough data on the “acute” (immediately after exposure) and “delayed” (after several days) effects of short-term (within several hours) perinatal normobaric hypoxia on the functioning of the peripheral vascular system of the systemic circulation in early ontogenesis in mammals. The aim of this work was to study the “acute” and “delayed” effects of a single normobaric hypoxia on the functioning of the arteries of the systemic circulation in early postnatal ontogenesis. The contractile responses of the saphenous artery of rats aged 10–14 days were studied in isometric myograph. Acute normobaric hypoxia (8% O2) was simulated for 2 hours in 10-day-old rat pups. The selected hypoxia regimen did not lead to changes in arterial contractile responses to the α1-adrenergic agonist methoxamine either immediately after exposure or several days later. Endothelium-dependent relaxation of arteries to acetylcholine also did not differ between groups. Hypoxia did not change the contribution of anticontractile pathways associated with nitric oxide and Kv7 channels, as well as the pro contractile role of Rho-kinase. Thus, according to the presented results, short-term normobaric hypoxia on the 10th day of life in rat pups does not lead to either “acute” or “delayed” changes in the regulation of the tone of the peripheral arteries of the systemic circulation in the early postnatal period.

The human body is faced with stress throughout ontogeny. At the stage of intrauterine development, the mother’s body serves as a source of resources and most of the humoral factors supporting the development of the fetus. In normal conditions, maternal stress-related humoral signals (e.g., cortisol) regulate fetal development; however, distress (excessive pathological stress) in the perinatal period leads to serious and sometimes irreversible changes in the developing brain. The mother being in an unfavorable psychoemotional state, toxins and teratogens, environmental conditions, and severe infectious diseases are the most common risk factors for the development of perinatal nervous system pathology in the modern world. In this regard, the challenge of modeling situations in which prenatal or early postnatal stresses lead to serious impairments to brain development and functioning is extremely relevant. This review addresses the various models of perinatal pathology used in our studies (hypoxia, exposure to valproate, hyperserotoninemia, alcoholization), and assesses the commonality of the mechanisms of the resulting disorders and behavioral phenotypes forming in these models, as well as their relationship with models of perinatal pathology based on the impact of psychoemotional stressors.

The human organism is faced with stressful influences during the entire ontogenesis. At the stage of intrauterine development, such influences are mediated mainly by factors associated with the maternal body. Normally, stress-mediated hormones (such as cortisol) regulate fetal formation; however, distress (excessive pathological stress) in the perinatal period leads to serious and, at times, irreversible changes in the developing brain. The unfavorable psycho-emotional status of the mother, toxins and teratogens, the ecological situation, the severe course of infectious diseases are the most common risk factors for the development of perinatal pathology of the nervous system in the modern world. In this regard, the problem of modeling situations when prenatal or early postnatal stressful influences lead to serious impairments to the development and functions of the brain is extremely urgent. The presented review is devoted to some models of perinatal pathology used in our studies (hypoxia, administration of valproate, hyperserotoninemia, alcoholization), the assessment of the common mechanisms of emerging disorders and behavioral phenotypes formed in these models, as well as their relationship with other ("classical") models of perinatal psycho-emotional stress.

Fetal or neonatal hypoxia is one of the main causes of neonatal mortality and results in long-term impairments to motor and cognitive functions. The aim of the present work was to study the effects of single-session normobaric hypoxia in rats aged 10 days (a model of premature birth in humans). Male and female Wistar rats were subjected to hypoxia for 2 h at an oxygen concentration of 8%. Control animals were kept in the same conditions but with a normal oxygen content. Levels of physical and motor development, movement and exploratory activity, and anxiety were assessed from day 11 to day 35 of life. Mortality due to exposure was 21.1%. Rats of both sexes showed slowing of weight gain and impaired production of motor reflexes. Impairments to movement coordination and balance ability were found in male but not female rats subjected to neonatal hypoxia. Female rats of adolescent age exposed to hypoxia showed increases in anxiety in the elevated plus maze test. The results provided evidence of sex dependence in the effects of neonatal hypoxia. The method used here can be regarded as a model of hypoxic brain damage in premature neonates.

Fetal or newborn hypoxia is a major cause of neonatal mortality and induces long-term motor and cognitive impairment. The aim of the presented work was to study the effects of an acute normobaric hypoxia in rats at the age of 10 days (a model of full-term human pregnancy). Male and female Wistar rats were exposed to hypoxic condition (oxygen content – 8 % for 2 h). Control animals were kept in the same conditions with normal oxygen content. From 11 to 35 days of life, the level of physical and motor development, motor and exploratory activity, and the level of anxiety were assessed. During hypoxic exposure the level of lethality was 21.1%. In rats of both sexes, there was a slowdown in weight gain and retarded performance of motor reflexes. Impaired motor coordination and ability to keep balance were recorded in male, but not in female rats underwent neonatal hypoxia. Adolescent female rats subjected to hypoxia demonstrated increased anxiety-like behaviour in elevated plus maze test. The results obtained indicate the gender-specific manner of the effects of neonatal hypoxia. The described method can be considered as a model of hypoxic brain damage in full-term newborns.

Perinatal hypoxia (PH) is one of the main factors having adverse influences on the development of the central nervous system. The sequelae of PH and the mechanisms of its development have been studied in animal experiments, mainly in rodents, such that there is still a need to develop more appropriate experimental models. The aim of the present work was to study the effects of single episodes of normobaric hypoxia in the offspring of C57BL/6 mice of both sexes. Mice aged two days were subjected to hypoxia for 2 h using an oxygen content of 8%. Control mice were kept in the same conditions but with a normal oxygen content. Levels of physical and motor development, motor and exploratory activity, and anxiety levels were determined from day 3 to day 31 of life. These studies showed that exposure led to higher levels of mortality in C57BL/6 mice, producing impairments to the establishment of sensorimotor reflexes, changes in behavior in the open field test, and a minor increase in anxiety in the elevated plus maze test. These results lead to the conclusion that models based on single episodes of normobaric hypoxia in mice can be used to study the pathophysiological and neurochemical mechanisms underlying neurological impairments in perinatal hypoxia.

Depression is a complex, heterogeneous and multifactorial disease with poorly understood pathophysiological mechanisms. Outbred Sprague Dawley (SD) and Wistar Han (WH) rats are widely used in biomedical research, in particular, in the model of chronic unpredictable stress (CUS) and in the inflammatory model of depression. However, the differences between SD and WH in these experimental models are not well studied. The aim of the present study was to compare alterations in the hedonic status, food consumption and body weight of male SD and WH rats obtained from Charles River Laboratories (Germany), in the CUS model (7 weeks) and in acute low-dose endotoxemia (single intraperitoneal injection of a low subseptic dose of LPS, 25 mu g/kg). Hedonic status was assessed using the sucrose preference test without prior food and water deprivation. Significant differences were found between SD and WH in the body weight gain, food consumption, locomotor and exploratory activity, and in the mass of the thymus. WH rats demonstrated a lower threshold of sucrose preference (0.3%) compared to SD rats (0.4%). The effects of both CUS and endotoxemia on body weight were more pronounced in SD rats. In endotoxemia, a decrease in hedonic status was more pronounced in WH rats. LPS-induced serum levels of TNF-alpha were higher in SD, and corticosterone was higher in WH (90 min after LPS). In the CUS model, changes in hedonic status and adrenal hypertrophy were detected only in SD rats, but thymic involution was detected only in WH. Significant differences in the physiological characteristics of Sprague Dawley and Wistar Han rats and the different sensitivity of their metabolic and hedonic status to stress and inflammation can have a significant impact on the results obtained in the models of the corresponding pathologies, as well as on their interpretation.

Перинатальная гипоксия (ПГ) является одним из основных факторов, вызывающих повреждения мозга новорожденных и последующие неврологические нарушения у детей.Современные технологии интенсивной терапии новорожденных, перенесших ПГ, позволили повысить выживаемость, но не привели к снижению неврологических нарушений, что вызвало увеличение заболеваемости среди взрослого населения.Экспериментальные модели ПГ на животных используются для выяснения клеточных и молекулярных механизмов и разработки новых терапевтических стратегий лечения последствий ПГ.Сопоставление уровня зрелости нервной системы человека и животных обосновывает использование неонатальной гипоксии у грызунов в качестве модели ПГ человека.Целью данного исследования явилось изучение изменений физического и моторного развития, а также поведения у крыс, перенесших острую нормобарическую гипоксию (ОНГ) на 2 постнатальный день (2 пнд) или 10 пнд.Методы: Работа проводилась на крысятах обоего пола.День рождения крысят принимали за нулевой день.Каждый выводок делили на 2 группы.Было проведено 2 серии экспериментов: (1) -крысят подвергали нормобарической гипоксии (8% О2, 2 часа, Т = 37 0 ) на 2 пнд (ОНГ-2; модель недоношенной беременности человека), (2) -на 10 пнд ((ОНГ-10), модель доношенной беременности человека).Регистрировали изменения массы тела и время становления моторных рефлексов.Уровень тревожности крыс оценивали в тесте «Приподнятый крестообразный лабиринт» (ПКЛ), способность к обучению в тесте «Лабиринт Барнса».Эксперименты проводились в соответствии с требованиями Комиссии по биоэтике МГУ.Результаты.Сразу после ОНГ-2 уровень летальности составил 8.3% (8.6 % самцов, 8.0 % самок), после ОНГ-10 -34.0%(40.2 % у самцов, 28.6 % у самок).У крысят, перенесших ОНГ как на 2, так и на 10 день, наблюдалось отставание по массе тела от контроля.Неонтатальная гипоксия вызывала замедление становления моторных рефлексов.Крысы, перенесшие гипоксию, демонсторировали задержку в выполнении рефлексов отрицательного геотаксиса (ОНГ-2 и ОНГ-10) и переворота на плоскости (ОНГ-2).ОНГ-2 не привела к изменению уровня тревожности в тесте ПКЛ у крыс в возрасте 1го месяца.ОНГ-10 не вызывала изменения поведения самцов, но приводила к повышению тревожности в ПКЛ у самок крыс.В тесте лабиринт Барнса во всех группах крыс наблюдалось значимое снижение числа ошибок и латентного периода реакции в течение 5-и дней обучения, что свидетельствует об успешной выработке рефлекса.Однако, при проверке обучения на 6-й день с повышенным уровнем стрессорной нагрузки, крысы группы ОНГ-2 совершали больше ошибок, чем контроль.В группе крыс ОНГ-10 отличий от контроля не наблюдалось.Следовательно, однократная неонатальная нормобарическая гипоксия у крыс в возрасте 2-х или 10 дней вызывает нарушения физического и моторного развития животных.Долговременные эффекты неонатальной гипоксии на

Perinatal hypoxia-ischaemia is one of the leading factors that negatively influence the development of the central nervous system. Our aim was to investigate the effects of sex on the outcomes of acute neonatal hypoxia (ANH) in rat pups. Male and female Wistar rats were exposed to a hypoxic condition (8% oxygen for 120 min) at postnatal day 2 (P2). Immediately after ANH an increase in HIF1-alpha gene expression was observed in the rat brains, independently of sex. Brain-derived neurotrophic factor (BDNF) and glutathione peroxidase-4 gene expression was increased in female animals only. Hypoxic pups of both sexes showed a decreased reduced/oxidised glutathione (GSH/GSSG) ratio in the blood and only males had an increased GSH content in the whole brain immediately after hypoxia. Furthermore, an increased BDNF content in the brain was found in both male and female rat pups at 0 h and in serum 4 h after hypoxia, but at 4 h after hypoxia only males had an increased BDNF level in the brain. Only hypoxic males displayed retarded performance in the righting reflex, but in a negative geotaxis test hypoxic pups of both sexes had an increased turnaround time. Moreover, hypoxic female but not male pups demonstrated less weight gain than control littermates for the entire observation period (until P18). These results demonstrate that ANH at P2 leads to both molecular and physiological impairments in a sex-specific manner and the described model could be used to represent mild hypoxic brain damage in very preterm infants.