Infantile Rats Research Articles

Febrile Seizures Cause Depression and Anxiogenic Behaviors in Rats.

Febrile seizure (FS) is a common type of seizure occurring in human during infancy and childhood. Although an epileptic seizure is associated with psychiatric disorders and comorbid diseases such as depression, anxiety, autism spectrum disorders, sleep disorders, attention deficits, cognitive impairment, and migraine, the causal relationship between FS and psychiatric disorders is poorly understood. The objective of the current study was to investigate the relationship of FS occurrence in childhood with the pathogenesis of anxiety disorder and depression using an FS rat model. We induced febrile seizures in infantile rats (11 days postnatal) using a mercury vapor lamp. At 3 weeks and 12 weeks after FS induction, we examined behaviors and recorded local field potentials (LFPs) to assess anxiety and depression disorder. Interestingly, after FS induction in infantile rats, anxiogenic behaviors and depression-like phenotypes were found in both adult and juvenile FS rats. The analysis of LFPs revealed that 4–7 Hz hippocampal theta rhythm, a neural oscillatory marker for anxiety disorder, was significantly increased in FS rats compared with their wild-type littermates. Taken together, our findings suggest that FS occurrence in infants is causally related to increased levels of anxiety-related behaviors and depression-like symptoms in juvenile and adult rodents.

Rapamycin Cannot Reduce Seizure Susceptibility in Infantile Rats with Malformations of Cortical Development Lacking mTORC1 Activation.

The mechanistic target of the rapamycin (mTOR) pathway is involved in cortical development. However, the efficacy of mTOR inhibitors in malformations of cortical dysplasia (MCD) outside of the tuberous sclerosis complex is unknown. We selected the MCD rat model with prenatal MAM exposure to test the efficacy of mTOR inhibitors in MCDs. We explored the early cortical changes of mTOR pathway protein expression in rats aged P15. We also monitored the early treatment effect of the mTOR inhibitor, rapamycin, on N-methyl-D-aspartate (NMDA)-induced spasms at P15 and their behavior in the juvenile stage. In vivo MR spectroscopy was performed after rapamycin treatment and compared with vehicle controls. There was no difference in mTORC1 pathway protein expression between MAM-exposed MCD rats and controls at P15, and prolonged treatment of rapamycin had no impact on NMDA-induced spasms despite poor weight gain. Prenatal MAM-exposed juvenile rats treated with rapamycin showed increased social approaching and freezing behavior during habituation. MR spectroscopy showed altered neurometabolites, including Gln, Glu+Gln, Tau, and Cr. Despite behavioral changes and in vivo neurometabolic alteration with early prolonged rapamycin treatment, rapamycin had no effect on spasms susceptibility in prenatal MAM-exposed infantile rats with MCD without mTORC1 activation. For MAM-exposed MCD rats without mTORC1 activation, treatment options outside of mTOR pathway inhibitors should be explored.

Anticonvulsive Effects and Pharmacokinetic Profile of Cannabidiol (CBD) in the Pentylenetetrazol (PTZ) or N-Methyl-D-Aspartate (NMDA) Models of Seizures in Infantile Rats.

In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infantile (12-days old) rats. Seizures were induced either with pentylenetetrazol (PTZ) or N-methyl-D-aspartate (NMDA). In parallel, brain and plasma levels of CBD and possible motor adverse effects were assessed in the righting reflex and the bar holding tests. CBD was ineffective against NMDA-induced seizures, but in a dose 60 mg/kg abolished the tonic phase of PTZ-induced generalized seizures. Plasma and brain levels of CBD were determined up to 24 h after administration. Peak CBD levels in the brain (996 ± 128 and 5689 ± 150 ng/g after the 10- and 60-mg/kg doses, respectively) were reached 1–2 h after administration and were still detectable 24 h later (120 ± 12 and 904 ± 63 ng/g, respectively). None of the doses negatively affected motor performance within 1 h after administration, but CBD in both doses blocked improvement in the bar holding test with repeated exposure to this task. Taken together, anti-seizure activity of CBD in infantile animals is dose and model dependent, and at therapeutic doses CBD does not cause motor impairment. The potential risk of CBD for motor learning seen in repeated motor tests has to be further examined.

Neonatal Exposure to Titanium Dioxide Nanoparticles Modulates the Redox Balance in Infantile and Adult Female Rats

Objectives: The aim of our study was to determine a possible relationship between the redox state of the organism and the exposure to TiO2 Nanoparticles (NPs). Design and methods: TiO2 NPs (1% or 10% LD50 TiO2) were intraperitoneally administered to female Wistar rats from the Postnatal Day 4 (PND4) to PND7. Rats were sacrificed on the PND15 (infantile rats) or after the PND220 (adult rats). In plasma, Antioxidant Capacity (TEAC), concentration of protein carbonyls and lipoperoxides were measured. Hemolysates were used to determine the changes in catalase, Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD) activities. Results: Young rats: 1% and 10% LD50 TiO2 induced the decrease in TEAC, lipoperoxide levels and Gluthione Peroxidase (GPx) activities and higher Superoxide Dismutase (SOD) activities in infantile rats, compared to controls. Adults: Significantly lower lipoperoxide levels, higher SOD and GPx activities were found in adults compared to young rats. 1% LD50 TiO2 significantly increased TEAC value and reduced SOD and GPX activities, but 10% LD50 TiO2 reduced TEAC compared to controls. Conclusion: Our results demonstrate that neonatal exposure to TiO2 NPs may modulate redox balance in female rats depending on the age, which might lead to alterations of their physiological functions.

The GluN2B-Selective Antagonist Ro 25-6981 Is Effective against PTZ-Induced Seizures and Safe for Further Development in Infantile Rats.

The GluN2B subunit of NMDA receptors represents a perspective therapeutic target in various CNS pathologies, including epilepsy. Because of its predominant expression in the immature brain, selective GluN2B antagonists are expected to be more effective early in postnatal development. The aim of this study was to identify age-dependent differences in the anticonvulsant activity of the GluN2B-selective antagonist Ro 25-6981 and assess the safety of this drug for the developing brain. Anticonvulsant activity of Ro 25-6981 (1, 3, and 10 mg/kg) was tested in a pentylenetetrazol (PTZ) model in infantile (12-day-old, P12) and juvenile (25-day-old, P25) rats. Ro 25-6981 (1 or 3 mg/kg/day) was administered from P7 till P11 to assess safety for the developing brain. Animals were then tested repeatedly in a battery of behavioral tests focusing on sensorimotor development, cognition, and emotionality till adulthood. Effects of early exposure to Ro 25-6981 on later seizure susceptibility were tested in the PTZ model. Ro 25-6981 was effective against PTZ-induced seizures in infantile rats, specifically suppressing the tonic phase of the generalized tonic–clonic seizures, but it failed in juveniles. Neither sensorimotor development nor cognitive abilities and emotionality were affected by early-life exposure to Ro 25-6981. Treatment cessation did not affect later seizure susceptibility. Our data are in line with the maturational gradient of the GluN2B-subunit of NMDA receptors and demonstrate developmental differences in the anti-seizure activity of the GluN2B-selective antagonist and its safety for the developing brain.

Study of the effect of Jian-Pi-Xiao-Shi formula on infantile rats with anorexia

Study of the effect of Jian-Pi-Xiao-Shi formula on infantile rats with anorexia

Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons.

Oxidative stress is one of the main proposed mechanisms involved in neuronal degeneration. To evaluate the consequences of oxidative stress on motor cortex pyramidal neurons during postnatal development, rats were classified into three groups: Newborn (P2–P7); infantile (P11–P15); and young adult (P20–P40). Oxidative stress was induced by 10 µM of cumene hydroperoxide (CH) application. In newborn rats, using the whole cell patch-clamp technique in brain slices, no significant modifications in membrane excitability were found. In infantile rats, the input resistance increased and rheobase decreased due to the blockage of GABAergic tonic conductance. Lipid peroxidation induced by CH resulted in a noticeable increase in protein-bound 4-hidroxynonenal in homogenates in only infantile and young adult rat slices. Interestingly, homogenates of newborn rat brain slices showed the highest capacity to respond to oxidative stress by dramatically increasing their glutathione and free thiol content. This increase correlated with a time-dependent increase in the glutathione reductase activity, suggesting a greater buffering capacity of newborn rats to resist oxidative stress. Furthermore, pre-treatment of the slices with glutathione monoethyl ester acted as a neuroprotector in pyramidal neurons of infantile rats. We conclude that during maturation, the vulnerability to oxidative stress in rat motor neurons increases with age.

The use of ex vivo ovary culture for assessment of alterations in steroidogenesis following neonatal exposure to poly(ethylene glycol)-block-polylactide methyl ether or titanium dioxide nanoparticles in Wistar rats.

Rapid development and widespread application of different types of nanoparticles (NPs) may result in increased exposure of humans and animals to NPs. Recently, reproductive toxicity due to NP exposure has become a major component of risk assessment. Current data have suggested that NPs may pose adverse effects on male and female reproductive health by altering normal testis and ovarian structure, and sex hormone levels. To detect possible alterations in steroidogenesis in adult and infantile rats following neonatal exposure to polymeric poly(ethylene glycol)-block-polylactide methyl ether (PEG-b-PLA) or titanium dioxide (TiO2) NPs, whole ovary cultures were used. Newborn female Wistar rats were intraperitoneally (i.p.) injected daily with two different doses of PEG-b-PLA NPs (20 and 40 mg/kg body weight, b.w.) or TiO2 NPs (1% LD50 TiO2=59.2 µg/kg b.w. and 10% LD50 TiO2=592 µg/kg b.w.) from postnatal day 4 (PND 4) to PND 7. The ovaries were collected on PND73 and PND15 of PEG-b-PLA- and TiO2 NP-treated rats, respectively, and their corresponding control animals. Minced ovaries were cultured in vitro in the absence (basal conditions) or presence of gonadotropins (follicle-stimulating hormone, FSH and luteinizing hormone, LH) and insulin-like growth factor-1 (IGF-1) (stimulated conditions) for 6 days. At indicated time intervals, culture media were collected for steroid hormone (progesterone, estradiol) analysis by specific radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) kits. Basal progesterone and estradiol secretion by ovaries from adult rats (PND73) were significantly decreased (p<0.01) in both PEG-b-PLA-treated groups after 3 days and 1 day of ex vivo ovary culture, respectively, compared with control group. With the presence of FSH/LH and IGF-1 in the culture medium, progesterone and estradiol production significantly increased (p<0.001) compared to basal levels. Stimulated progesterone production was significantly decreased (p<0.05) in PEG-b-PLA40-treated group after 3 days of culture compared with controls. After ex vivo culture of rat ovaries collected on PND15, basal progesterone and estradiol levels measured in the culture media did not differ between control and both TiO2 NP-treated groups. The ovaries from rats neonatally exposed to both doses of TiO2 NPs failed to respond to FSH/IGF stimulation in progesterone secretion at all time intervals. The obtained results indicate that neonatal exposure to NPs in female rats may alter ovarian steroidogenic output (steroid hormone secretion) and thereby might subsequently induce perturbation of mammalian reproductive functions. Possible mechanisms (induction of oxidative stress, inflammation) of adverse effects of NPs on ovarian function should be further elucidated.

Effect of penehyclidine hydrochloride on hyperoxia-induced acute lung injury and the relationship with endoplasmic reticulum stress-dependent apoptosis in infantile rats

Objective To evaluate the effect of penehyclidine hydrochloride on hyperoxia-induced acute lung injury and the relationship with endoplasmic reticulum stress-dependent apoptosis in infantile rats. Methods Ninety-six clean-grade male infantile Sprague-Dawley rats, weighing 40-50 g, aged 14 days, were allocated into 4 groups (n=24 each) using a random number table method: control group (C group), penehyclidine hydrochloride group (P group), hyperoxia group (HO group) and hyperoxia plus penehyclidine hydrochloride group (HP group). Infantile rats were intravenously injected with penehyclidine hydrochloride (0.3 mg/kg) at the same time point every day for 3 consecutive days in P and HP groups.Infantile rats were injected with the equal volume of normal saline instead of penehyclidine hydrochloride in C and H groups.Acute lung injury was induced by inhaling oxygen at concentration greater than 90% for 72 h starting from 4th day after administration.Infantile rats were sacrificed at the end of inhaling, and lungs were removed for examination of the pathological changes and for determination of weight to dry weight ratio (W/D ratio), index of quantitative evaluation for alveolar damage (IQA), pneumonocyte apoptosis (using TUNEL), expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein(CHOP) protein and mRNA in lung tissues (by Western blot or using reverse transcription-polymerase chain reaction). The mitochondrial injury score was assessed, and apoptotic index (AI) was determined. Results Compared with C group, the W/D ratio, IQA, AI and mitochondrial injury score were significantly increased, and the expression of GRP78 and CHOP protein and mRNA was up-regulated in HO and HP groups(P 0.05). Compared with HO group, the W/D ratio, IQA, AI and mitochondrial injury score were significantly decreased, the expression of GRP78 and CHOP protein and mRNA was down-regulated (P<0.05), and the pathological changes of lung tissues were significantly attenuated in HP group. Conclusion Penehyclidine hydrochloride can mitigate hyperoxia-induced acute lung injury, and the mechanism may be related to inhibiting endoplasmic reticulum stress-dependent apoptosis in infantile rats. Key words: Cholinergic antagonist; Acute lung injury; Hyperoxia; Endoplasmic reticulum stress; Apoptosis

Doublecortin Expression in the Olfactory Bulb and Rostral Stream in Infantile Rats after Exposure to Neurotoxin

The aim of the study was to investigate changes of neuroblasts’ numeral destiny in rats’ olfactory bulb and rostral migratory stream after neurotoxic action in infant age.Material and methods. The distribution of DCX, a marker of immature neurons, was studied to reveal the dynamics of its expression in the evolutionary period of ontogenesis in olfactory bulbs and rostral migratory stream in 30, 60, 90, and 180-day-old rats. Modeling of neurotoxic effects was carried out by three times injections of capsaicin on the 30–32 day of life in a total dose of 120 mg/kg. The material for the study was sampled on the 15-, 30- and 60th days of the experiment. The marker was detected on parasagittal paraffin sections, taking into account the layers of the olfactory bulb. The numerical density of DCX+ neurons (pcs/mm2) and their part in the total number of cells were determined.Results. The standard age indicators of the numerical density of immature neurons and their share in the cell population, as well as similar indicators for two months after toxic effects, were established. The administration of toxic doses of capsaicin causes a massive death of mature neurons. Compensatory reaction manifested by activation of neurogenesis in the brain stem niches and an increase in the numerical density neuroblasts in the rostral stream.Conclusions. Activation of neurogenesis during neurodegeneration causes an increase in the number of DCX + neuronal progenitors in the olfactory bulb after 30 days after exposure and maintaining high levels until the end of observation.

L-Arginine and L-Citrulline Supplementation Have Different Programming Effect on Regulatory T-Cells Function of Infantile Rats.

Arginine is a semiessential amino acid in healthy adult human, but is essential for preterm, newborn or critically ill patients. Arginine can be supplied from our diet or de novo synthesis from citrulline. In conditions of sepsis or endotoxemia, arginine may be deficient and be accompanied with altered immune response. L-arginine supplementation can ameliorate dysregulated immune condition and improve prognosis. Many studies had tried L-arginine or L-citrulline supplementation to examine the effect on immune response in the adult population. Few had studied on the young children. In this study, we determined the effect of L-arginine and L-citrulline supplementation on the immune response of infantile rats. Male infantile rats received normal saline, L-arginine (200 mg/kg/day) or L-citrulline (200 mg/kg/day) intraperitoneally over postnatal day 8 to day 14. The infantile rats were then sacrificed. The blood was analyzed while the spleen was indicated for immune analysis after stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS). We found L-arginine supplementation enhanced Th1 immune response by increasing IFN-γ production. Both the L-arginine and L-citrulline therapy can modulate regulatory T-cell (Treg) immune effects by increasing the IL-10 level. Only the L-citrulline group showed a TGF-β1 increase. Both L-arginine and L-citrulline therapy were also noted to decrease SMAD7 expression and enhance SIRT-1 abundance. However, FOXP3 expression was only modulated by L-citrulline treatment. We then concluded that L-arginine and L-citrulline supplementation can modulate the regulatory T-cells function differently for infantile rats.

The sex differences of the behavior response to early Life immune stimulation: Microglia and astrocytes involvement

It is well known that inflammatory challenge during the prenatal period results in permanent changes in glial cells and behavior in adulthood. However, it is unknown whether inflammatory challenge during the infantile period may have permanent sexually-dimorphic effects on microglia and astrocytes in vivo, which in turn may be associated with sex differences in adult behavior. In this study, we have evaluated whether postnatal injection of lipopolysaccharide (LPS; 250μg/kg, i.p. on postnatal day 14) induces depressive and less anxiety-like behaviors, glial cell activation, pro-inflammatory cytokine (TNF-alpha) secretion and sexually dimorphic responses in adulthood. Postnatal day 14 (P14) male and female Wistar rats received an intraperitoneal (ip) injection of LPS or PBS. Three months later, animals were tested in the Open Field (OF), the Elevated Plus Maze (EPM) and the Forced Swimming Test (FST) to assess the level of anxiety and depression-like behavior. Hippocampal proinflammatory cytokine TNF-alpha concentration and the number of astrocytes and microglia were estimated in the dentate gyrus, CA1, and CA3 in two regions of the hippocampus (ventral and dorsal). Our results showed that the administration of LPS resulted in less anxiety and depression-like behavior in males but not in females. However, the LPS-administration increased the number of microglia in the dorsal and ventral hippocampus areas in females more than male, while no significant differences in TNFα level had been detected between the LPS-rats treated and their controls. Interestingly, LPS resulted in an increase in the number of astrocytes in both areas of the hippocampus in a female. While in a male, our results showed a decrease in astrocytes number in the dorsal hippocampus, but no significant differences observed in ventral hippocampus.These findings indicate that an immune challenge in infantile rats induces a ventral and dorsal hippocampus damage in female more than in male, without affecting significantly the affective behavior changes in the female. The results also showed that small changes in the male hippocampus can affect the behavior and induce a depression-like behavior.

Acupuncture at ST36 exerts neuroprotective effects via inhibition of reactive astrogliosis in infantile rats with hydrocephalus

BackgroundAcupuncture has been associated with improved cerebral circulation, analgesia, neuromodulatory function and neurogenesis. In particular, acupuncture at ST36 has been widely used in several central nervous system (CNS) disorders, including...

Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus

Objective/Aim: Hydrocephalus is defined as an incapacitating neurological disorder characterized by ventricular enlargement in children, but the effects of melatonin on this hydrocephalus have not yet been fully elucidated. In the present experiment, we attempted to investigate the effects of exogenous melatonin administration on hydrocephalus-induced hippocampal changes in infantile rats. Methods: In this study, we randomly divided 45 Swiss albino rats aged 2 weeks into 3 groups: group I, the control group received a sham injection with needle insertion only; groups II and III were given kaolin injections before treatment – group II, the hydrocephalus group, was treated with an isotonic NaCl solution, and group III, the hydrocephalus plus melatonin group, was treated with 0.5 mg/100 g body weight of exogenous melatonin. Both immunohistochemical and histological analyses were performed after hydrocephalus induction and melatonin administration. Immunohistochemical staining consisted anti-glial fibrillary acidic protein staining. The TUNEL technique was used for defining quantitate apoptosis. Results: Melatonin administration significantly attenuated chronic hydrocephalus-induced histopathological changes in the hippocampal subregions of infantile rats. Compared to hydrocephalic rats treated with saline solution, melatonin significantly decreased the number of apoptotic cells and pyknotic index values of each hippocampal subregion after the kaolin-induced hydrocephalus (p < 0.001). Conclusion: The present results demonstrate that the chronic hydrocephalus-induced histopathological changes in the hippocampus were partially reversible with melatonin treatment, suggesting its neuroprotective effects in infantile rats. However, these findings need to be confirmed by further experimental studies and clinical trials.

Effect of Vitamin D on monocyte/macrophage chemoattractant protein and macrophage infiltration in adipose tissue of infantile rats with obesity

Objective To investigate the effect of Vitamin D (VitD) on intraperitoneal fat coefficient, monocyte/macrophage chemoattractant protein and macrophage infiltration in adipose tissue of infantile rats with obesity. Methods A total of 45 weanling female SD rats were randomly divided into control group(group N), obesity model group(group OB) and VitD intervention group(group VitD), and each group had 15 rats.The rats of group N were fed with basic diet, and the rats in group OB and group VitD were fed with high-fat diet.The rats of group VitD were administrated intragastrically with VitD 5 μg/(kg·d)(equivalent to 400 IU VitD for human infants) for 6 weeks, while the rats of group OB and group N were given plant oil [5 mL/(kg·d)] for 6 weeks instead.The body weight of rats were recorded once every week, and Lee′s indexes were calculated.The fat mass in enterocoelia were weighted after 6 weeks.The levels of monocyte chemoattractant protein-1(MCP-1) and macrophage inflammatory protein-1α(MIP-1α) in serum were detected by adopting enzyme-linked immunosorbent assay.The specimens of adipose tissue were observed and the number of adipocyte was counted through hematoxylin-eosin stain.The protein expressions of MCP-1, MIP-1α and F4/80 in adipose tissue were determined by immunohistochemistry, and the mRNA expressions of MCP-1, MIP-1α and nuclear factor (NF)-κB in adipose tissue were determined by real time quantitative polymerase chain reaction(qPCR), then the correlation analysis with body weight, Lee′s index and fat mass in enterocoelia were conducted. Results After 6 weeks with high-fat diet, the body weight, intraperitoneal fat coefficient, serum levels of MCP-1 and MIP-1α in group OB[(244.1±16.2) g, (3.25±0.63)%, (2 275.2±229.3) ng/L, (190.4±61.9) ng/L] significantly increased compared with those of group N[(224.2±10.9) g, (2.43±0.47)%, (1 522.1±577.1) ng/L, (63.6±31.6) ng/L] and group VitD[(214.0±12.5) g, (2.04±0.64)%, (1 863.4±477.0) ng/L, (120.3±29.5) ng/L], and the differences were significant (all P 0.05). Conclusions VitD supplement can suppress the obesity induced by high-fat-diet, and the possible mechanism is that VitD reduce the expression of monocyte/macrophage chemoattractant protein and macrophage infiltration in adipose tissue through regulating NF-κB signal pathway. Key words: Intraperitoneal adipose tissue; Monocyte chemoattractant protein-1; Macrophage inflammatory protein-1α; Macrophage; Vitamin D; Infantile rat

THE USE OF HYALURONIC ACID FOR THE TREATMENT OF ADHESIVE INTESTINAL OBSTRUCTION IN CHILDREN

The purpose of the explore the possibility of using hyaluronic acid for the treatment of intraperitoneally adhesions in experiment and at children. We used hyaluronic acid – “Defensal”. To achieve the goal, we have done the series of experimental studies on 60 infantile rats, weighing 100±20 mg. Animals were divided into two groups: group – modeling of intra-abdominal adhesions (25 rats); group II – treatment of adhesions. In II group of rats carried out the separation of adhesions on the 30th day of the experiment. For the treatment of adhesions was performed by flooding the abdominal cavity of the solution “Defensal” with the amount of 8 ml (25 rats). 10 rats were control group. The decapitation of the rats were on the 30th day. The parts of terminal ileum (TI) were taken to study morphological changes of the wall ileum and APUD-system (system neuro-endocrine regulation of the gastrointestinal tract). There were two reactions to identify secretory granules into the apudocyte. The argyrophil Grimelius and the argentophil MassonHamperlmethods were carried out. 84 children were operated on AIO. The children were divided into two groups. I group were “Defensal” were not to use (56 patients). II group were “Defensal” to use (28 patients). The follow-up of children from 1 to 4 years. In the group of rats using “Defensal”, there has been an absence of adhesions in 42.86% of cases. The adhesions isolated spikes, that will not deform the intestine were identified in 42.86%.The multiple adhesions that not to deform intestine were in 14.28%. The study of tissue fibrinolytic activity of TI (was not involved and involved into adhesions) were showed the tendency to its increase when using the solution of “Defensal” but not reaching the data control. In the simulation of adhesions (I group) reported a decrease in the number apudocytes and decrease in their functional activity as evidenced by the size of argyrophilic granules. In the II group were coloring of the test material by Grimelius in the glands of the mucous membrane a sufficient number apudocytes was found. In the I group (56 children) in the first year after surgery with adhesion syndrome turned 13 (23.21%) children, up to 4 years – 20 (35.71%) patients. In the II group (28 children) adhesion syndrome (cured conservatively) over 2.5 years postoperative period turned 2 (7.14%) patients, indicating the effectiveness of “Defensal” for the purpose for treatment of the adhesions abdominal cavity at children.

The presence of VEGF and Notch2 during preantral-antral follicular transition in infantile rats: Anatomical evidence and its implications

Folliculogenesis is a process that depends on angiogenesis, in which VEGF and Notch signaling pathway members are involved. Although this pathway is present in preantral and antral follicular structures during the second stage of folliculogenesis, this association has not been described. Therefore, this study aimed to identify VEGF and Notch2 in ovary structures of infantile rats after induction of follicular development with a gonadotropin stimulus. In order to explore this possibility we analyzed rat ovary morphology from days 10–25 after birth; subsequently, the transition from preantral follicle to an antral stage was analyzed by the induction of follicular development with equine chorionic gonadotropin (eCG) and VEGF and Notch were identified in the rat ovary by fluorescence. The histological analysis revealed that the ovary of a 10-day-old rat has the highest percentage of preantral follicles and based on this a 10IU eCG dose promoted an increase in the number of antral follicles, as well as a decrease in the number of preantral follicles, related to which there was an increase in ovary weight and size. In addition, a higher concentration of circulating estradiol was observed, proliferation of granulosa cells in both follicle groups was stimulated, and the accumulation of VEGF in granulosa and theca cells and in the antral follicle oocyte was increased (p<0.05), whereas the presence of Notch2 was limited to mural granulosa cells, in granulosa cells that formed the cumulus oophorus and in the oocyte of both groups of follicles. The multiple correspondence analysis allowed us to support an association between VEGF and Notch2 during the transition from preantral to antral follicles in the ovary of an infantile rat.

Effects of Afobazole on Postnatal Development of Rat Offspring.

Physical development, development of sensory and motor reflexes, behavioral and mnestic patterns were studied infantile and juvenile rat pups born by female rats receiving Afobazole during pregnancy. Physical development and development of sensory and motor reflexes in rats were completed without pathologies by the age of 2 months. During the infantile period, the rat pups demonstrated reduced body weight gain, delayed eye opening and pupillary response formation, decreased muscle force, and suppressed motor behavior. During the juvenile period, body weight gain and development of motor behavior were intensified. Females demonstrated later vagina opening and poorer mnestic responses. In males, the terms of sexual maturation were unchanged and processes of learning and memory retrieval were not impaired.

Effect of Neonatal Exposure to Poly(Ethylene Glycol)-block-Poly(Lactic Acid) Nanoparticles on Oxidative State in Infantile and Adult Female Rats.

Our goal was to evaluate the potential health risk of the polymeric NP, poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA), from the view of redox imbalance of the organism in two different life stages. Female Wistar rats were neonatally administered intraperitoneally with PEG-b-PLA NPs [20 mg/kg of b.w. (PEG20) or 40 (PEG40) mg/kg of b.w.] from postnatal day 4 (PND4) to PND7. We measured antioxidant capacity (TEAC), level of protein carbonyls and lipoperoxides in plasma, activities of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD) in hemolysates of infantile (sacrificed on PND17) and adult (sacrificed after PND176) rats. Compared to controls, neonatal PEG40 exposure induced a significant TEAC reduction in the infantile rats. Protein carbonyls and lipoperoxide levels were not affected after any dose of PEG-b-PLA NP administration. In adult rats, PEG20 administration caused a significant decrease of protein carbonyl levels compared to controls. In infantile rats, both doses of PEG-b-PLA NP administration increased catalase, Gpx, and SOD activities compared to controls. Surprisingly, in adult rats, the activities of Gpx and SOD decreased significantly after administration of both doses of PEG-b-PLA NPs. Obtained data indicate a possible age-related association between the oxidative status and neonatal PEG-b-PLA NP administration in female rats.

Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach

Thyroid hormones (TH) are one of the key factors for normal prenatal development in mammals. Previously, we showed that subclinical maternal hypothyroidism leads to premature atresia of ovarian follicles in female rat offspring in the pre-pubertal and pubertal periods. The influence of decreased concentration of TH on primordial follicles pool formation during neonatal and early infantile period of rat pups was not investigated previously. Maternal hypothyroidism during pregnancy has irreversible negative influence on primordial follicles pool formation and population of resting oocytes in female rat offspring. The study was done on neonatal and early infantile control (n-10) and hypothyroid (n-10) female rat pups derived from control (n-6) and propylthiouracil (PTU) treated pregnant dams (n-6), respectively. Ovaries of all pups were removed and processed for light and transmission electron microscopy (TEM). Number of nests, oogonia and oocytes per nest, primordial, primary, secondary and preantral follicles were determined. Screening for overall calcium presence in ovarian tissue was done using Alizarin red staining. Morphology and volume density of nucleus, mitochondria and smooth endoplasmic reticulum (sER) in the oocytes in primordial follicles was also assessed. Caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), both markers for apoptosis, and proliferating cell nuclear antigen (PCNA) for proliferation were determined in oocytes and granulosa cells in different type of follicles. In neonatal period, ovaries of hypothyroid pups had a decreased number of oogonia, oocytes and nests, an increased number of primordial follicles and a decreased number of primary and secondary follicles, while in early infantile period, increased number of primary, secondary and preantral follicles were found. Alizarin red staining was intense in hypothyroid neonatal rats that also had the highest content of dilated sER. Number of mitochondria with altered morphology in both groups of hypothyroid pups was increased. Apoptosis markers have not shown significant difference between groups but PCNA had an increased expression in the oocytes and granulosa cells in primordial follicles of hypothyroid rats. Light and electron microscopy analysis indicate that previously detected premature ovarian follicular atresia in pre-pubertal and pubertal hypothyroid rats is preceded with premature formation of primordial follicles followed by slight changes on sER and mitochondria in examined oocytes, and increased expression of PCNA.