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We investigated plasma concentrations of adrenocorticotropic hormone (ACTH), corticosterone and serotonin in juvenile and adult rats, as well as raphe serotonin levels and behavioral responses in the open field and elevated plus maze tests in adult rats, exposed to three sessions of neonatal hypobaric hypoxia (360 mm Hg, 2 h each, once a day) within days 8–10 postpartum. This noninvasive rat model of neonatal hypoxia (NH) simulates mild perinatal hypoxic injury in human fetuses and premature infants. At 3 months of age, NH-exposed rats exhibited reduced exploratory behavior and increased anxiety in both behavioral tests, accompanied by decreased serotonin levels in the raphe nuclei. In adult NH-exposed rats, plasma corticosterone and serotonin levels remained unaltered, while ACTH levels showed a significant decrease. Our findings suggest that early postnatal hypoxic stress disrupts the serotoninergic system and modifies the hypothalamic–pituitary–adrenocortical axis, leading to long-lasting behavioral deficits in adult rats. [ABSTRACT FROM AUTHOR]

Aim: Preterm infants frequently experience short apnoeas and periodic breathing. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if apnoea and periodic breathing were associated with changes in autonomic control assessed using heart rate variability, thus exacerbating the consequences of respiratory disturbance. Methods: Forty very preterm infants (15 M/25 F) were studied at 34.3 weeks post‐menstrual age with daytime polysomnography. Total power, low frequency (LF, sympathetic+parasympathetic activity) high frequency (HF, parasympathetic activity) and LF/HF (sympathovagal balance) were calculated. Results: Infants were divided into those with above and below the median total sleep time spent with respiratory events: Active sleep (AS) 13%, Quiet sleep (QS) 10%. In AS, including respiratory events, Total power (p < 0.05) and HF power (p < 0.05) were higher in the above median group. During AS excluding respiratory events, Total power (p < 0.05) and HF power (p = 0.061) were higher and LF power (p < 0.01) and LF/HF (p < 0.05) were lower in the above median group. There were no differences in HRV parameters in QS. Conclusion: This study provides new evidence that short apnoeas, particularly periodic breathing, which is currently not detected or treated in the neonatal unit can affect autonomic cardiovascular control. [ABSTRACT FROM AUTHOR]

Introduction and aim. The objective of the study was to evaluate the effect of Mentat® an herbal formulation in experimental models of hypoxia-induced attention deficit hyperactive disorder (ADHD) like behavior in rats. Material and methods. Mentat® was evaluated at the dose of 100 and 200 mg/kg body weight. per oral., in two experimental models of hypoxia in Wistar rats. In the first model, after parturition, on a postnatal day 2 (PND-2), the pups were subjected to hypoxic exposure for 10 minutes to induce neonatal hypoxia. Pups were weaned from dams on PND-21 and subjected to drug treatments for 10 days. In the second model, phenytoin 150 mg/kg. b.wt. p.o. was administered orally to all pregnant animals throughout gestation to induce intrauterine hypoxia. Pups were subjected to assigned treatments after weaning. Behavioral and biochemical parameters relevant to ADHD were assessed. Results. In the positive control group, hypoxic exposure resulted in significant changes in cognitive and neurologic skills compared to normal control. Open field test, elevated plus maze test, and Acetylcholine esterase levels showed a significant increase in positive control compared to normal control. In treatment groups, there was a dose-dependent decrease in all the above parameters compared to positive control. Dopamine and Nor-epinephrine levels in brain homogenate were decreased in positive control which subsequently increased with Mentat® treatment. Conclusion. Mentat® showed a neuroprotective effect in different experimental models of ADHD. It may be recommended for the effective/preventive management of ADHD, especially associated with memory impairment and neurologic conditions. [ABSTRACT FROM AUTHOR]

Neuregulin 1 (NRG1)–induced activation of ErbB4 in parvalbumin (PV) inhibitory interneurons is reported to serve as a critical endogenous negative-feedback mechanism to repress brain epileptogenesis. Here, we investigated the seizure susceptibility and the role of NRG1-ErbB4 signaling in PV interneurons in the suppression of epileptic seizures for rats subject to early life hypoxia. Neonatal postnatal day 5 (P5) rats were exposed to intermittent hypoxia (IH) or control (CON) room air for 10 days. In the prefrontal cortex (PFC) of P54 rats, we determined the impact of neonatal IH exposures on the expression of PV, NRG1, ErbB4, and phosphorylated ErbB4 (p-ErbB4) during the seizure induction. Seizure susceptibility tests with the common convulsant agent pentylenetetrazole (PEN) at P54 revealed that rats subject to neonatal hypoxia exposure developed faster and more serious epileptic seizures. Neonatal IH exposures (1) decreased the number of PV cells in the PFC of P54 rats; (2) interrupted the expression of NRG1 gene; and (3) altered the activity of NRG1 on PV interneurons in the PFC after the seizure induction. Intracerebroventricular delivery of exogenous NRG1 before seizure induction by PEN significantly reduced the seizure susceptibility for neonatal IH-exposed rats. The ErbB4 inhibitor AG1478 inhibited the exogenous NRG1's effects on seizure susceptibility. Environmental enrichment (EE) rescued the abovementioned pathophysiological alterations and significantly attenuated the epileptic seizures after the seizure induction for neonatal IH-exposed rats. Our study indicated early life hypoxia exposure might increase the seizure susceptibility for rats and contribute to pathophysiological dysfunction of NRG1-ErbB4 signaling in PV interneurons in the suppression of epileptic seizures. EE might attenuate the increased seizure susceptibility for neonatal IH-exposed rats through rescuing pathophysiological alterations of NRG1-ErbB4 signaling in PV interneurons. [ABSTRACT FROM AUTHOR]

Small remnants of the right valve of the sinus venosus are commonly found in adults, but the incidence and risk associated with these embryonic remnants in neonates are not well studied. The following report describes a cyanotic neonate with a large Eustachian valve remnant creating a functional cor triatriatum dexter who was initially diagnosed with persistent pulmonary hypertension of the newborn. The cyanosis in this infant improved over the first postnatal week with conservative management, but she suffered multifocal subcortical stroke, likely related to her intracardiac shunt. The clinical presentation and questions regarding long-term management of this rare diagnosis are explored. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia (PA) is a relevant cause of death at the time of labour, and when survival is stabilised, associated with short- and long-term developmental disabilities, requiring inordinate care by health systems and families. Its prevalence is high (1 to 10/1000 live births) worldwide. At present, there are few therapeutic options, apart from hypothermia, that regrettably provides only limited protection if applied shortly after the insult. PA implies a primary and a secondary insult. The primary insult relates to the lack of oxygen, and the secondary one to the oxidative stress triggered by re-oxygenation, formation of reactive oxygen (ROS) and reactive nitrogen (RNS) species, and overactivation of glutamate receptors and mitochondrial deficiencies. PA induces overactivation of a number of sentinel proteins, including hypoxia-induced factor-1α (HIF-1α) and the genome-protecting poly(ADP-ribose) polymerase-1 (PARP-1). Upon activation, PARP-1 consumes high amounts of ATP at a time when this metabolite is scarce, worsening in turn the energy crisis elicited by asphyxia. The energy crisis also impairs ATP-dependent transport, including glutamate re-uptake by astroglia. Nicotinamide, a PARP-1 inhibitor, protects against the metabolic cascade elicited by the primary stage, avoiding NAD exhaustion and the energetic crisis. Upon re-oxygenation, however, oxidative stress leads to nuclear translocation of the NF-κB subunit p65, overexpression of the pro-inflammatory cytokines IL-1β and TNF-α, and glutamate-excitotoxicity, due to impairment of glial-glutamate transport, extracellular glutamate overflow, and overactivation of NMDA receptors, mainly of the extrasynaptic type. This leads to calcium influx, mitochondrial impairment, and inactivation of antioxidant enzymes, increasing further the activity of pro-oxidant enzymes, thereby making the surviving neonate vulnerable to recurrent metabolic insults whenever oxidative stress is involved. Here, we discuss evidence showing that (i) inhibition of PARP-1 overactivation by nicotinamide and (ii) inhibition of extrasynaptic NMDA receptor overactivation by memantine can prevent the short- and long-term consequences of PA. These hypotheses have been evaluated in a rat preclinical model of PA, aiming to identify the metabolic cascades responsible for the long-term consequences induced by the insult, also assessing postnatal vulnerability to recurrent oxidative insults. Thus, we present and discuss evidence demonstrating that PA induces long-term changes in metabolic pathways related to energy and oxidative stress, priming vulnerability of cells with both the neuronal and the glial phenotype. The effects induced by PA are region dependent, the substantia nigra being particularly prone to cell death. The issue of short- and long-term consequences of PA provides a framework for addressing a fundamental issue referred to plasticity of the CNS, since the perinatal insult triggers a domino-like sequence of events making the developing individual vulnerable to recurrent adverse conditions, decreasing his/her coping repertoire because of a relevant insult occurring at birth. [ABSTRACT FROM AUTHOR]

The hypothesis of enhanced vulnerability following perinatal asphyxia was investigated with a protocol combining in vivo and in vitro experiments. Asphyxia-exposed (AS) (by 21 min water immersion of foetuses containing uterine horns) and caesarean-delivered control (CS) rat neonates were used at P2-3 for preparing triple organotypic cultures (substantia nigra, neostriatum and neocortex). At DIV 18, cultures were exposed to different concentrations of HO (0.25-45 mM), added to the culture medium for 18 h. After a 48-h recovery period, the cultures were either assessed for cell viability or for neurochemical phenotype by confocal microscopy. Energy metabolism (ADP/ATP ratio), oxidative stress (GSH/GSSG) and a modified ferric reducing/antioxidant power assay were applied to homogenates of parallel culture series. In CS cultures, the number of dying cells was similar in substantia nigra, neostriatum and neocortex, but it was several times increased in AS cultures evaluated under the same conditions. A HO challenge led to a concentration-dependent increase in cell death (>fourfold after 0.25 mM of HO) in CS cultures. In AS cultures, a significant increase in cell death was only observed after 0.5 mM of HO. At higher than 1 mM of HO (up to 45 mM), cell death increased several times in all cultures, but the effect was still more prominent in CS than in AS cultures. The cell phenotype of dying/alive cells was investigated in formalin-fixed cultures exposed to 0 or 1 mM of HO, co-labelling for TUNEL (apoptosis), MAP-2 (neuronal phenotype), GFAP (astroglial phenotype) and TH (tyrosine hydroxylase; for dopamine phenotype), counterstaining for DAPI (nuclear staining), also evaluating the effect of a single dose of nicotinamide (0.8 nmol/kg, i.p. injected in 100 μL, 60 min after delivery). Perinatal asphyxia produced a significant increase in the number of DAPI/TUNEL cells/mm, in substantia nigra and neostriatum. One millimolar of H0 increased the number of DAPI/TUNEL cells/mm by ≈twofold in all regions of CS and AS cultures, an effect that was prevented by neonatal nicotinamide treatment. In substantia nigra, the number of MAP-2/TH-positive cells/mm was decreased in AS compared to CS cultures, also by 1 mM of H0, both in CS and AS cultures, prevented by nicotinamide. In agreement, the number of MAP-2/TUNEL-positive cells/mm was increased by 1 mM HO, both in CS (twofold) and AS (threefold) cultures, prevented by nicotinamide. The number of MAP-2/TH/TUNEL-positive cells/mm was only increased in CS (>threefold), but not in AS (1.3-fold) cultures. No TH labelling was observed in neostriatum, but 1 mM of HO produced a strong increase in the number of MAP-2/TUNEL-positive cells/mm, both in CS (>2.9-fold) and AS (>fourfold), decreased by nicotinamide. In neocortex, HO increased the number of MAP-2/TUNEL-positive cells/mm, both in CS and AS cultures (≈threefold), decreased by nicotinamide. The ADP/ATP ratio was increased in AS culture homogenates (>sixfold), compared to CS homogenates, increased by 1 mM of H0, both in CS and AS homogenates. The GSH/GSSG ratio was significantly decreased in AS, compared to CS cultures. One millimolar of HO decreased that ratio in CS and AS homogenates. The present results demonstrate that perinatal asphyxia induces long-term changes in metabolic pathways related to energy and oxidative stress, priming cell vulnerability with both neuronal and glial phenotype. The observed effects were region dependent, being the substantia nigra particularly prone to cell death. Nicotinamide administration in vivo prevented the deleterious effects observed after perinatal asphyxia in vitro, a suitable pharmacological strategy against the deleterious consequences of perinatal asphyxia. [ABSTRACT FROM AUTHOR]

While extensive studies report that neonatal hypoxia-ischemia (HI) induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d) rat pups to systemic hypoxia (3.5 h), a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg) was injected intraperitoneally (i.p.) 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg) minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS), indicated by presence of C-C chemokine receptor type 2 (CCR2+)/CD11b+CD45+ positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker). Interrupted blood-brain barrier (BBB), hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response. [ABSTRACT FROM AUTHOR]

Perinatal asphyxia (PA) is associated to delayed cell death, affecting neurocircuitries of basal ganglia and hippocampus, and long-term neuropsychiatric disabilities. Several compensatory mechanisms have been suggested to take place, including cell proliferation and neurogenesis. There is evidence that PA can increase postnatal neurogenesis in hippocampus and subventricular zone (SVZ), modulated by dopamine, by still unclear mechanisms. We have studied here the effect of selective dopamine receptor agonists on cell death, cell proliferation and neurogenesis in organotypic cultures from control and asphyxia-exposed rats. Hippocampus and SVZ sampled at 1-3 postnatal days were cultured for 20-21 days. At day in vitro (DIV) 19, cultures were treated either with SKF38393 (10 and 100 µM, a D agonist), quinpirole (10 µM, a D agonist) or sulpiride (10 μM, a D antagonist) + quinpirole (10 μM) and BrdU (10 μM, a mitosis marker) for 24 h. At DIV 20-21, cultures were processed for immunocytochemistry for microtubule-associated protein-2 (MAP-2, a neuronal marker), and BrdU, evaluated by confocal microscopy. Some cultures were analysed for cell viability at DIV 20-21 (LIVE/DEAD kit). PA increased cell death, cell proliferation and neurogenesis in hippocampus and SVZ cultures. The increase in cell death, but not in cell proliferation, was inhibited by both SKF38393 and quinpirole treatment. Neurogenesis was increased by quinpirole, but only in hippocampus, in cultures from both asphyxia-exposed and control-animals, effect that was antagonised by sulpiride, leading to the conclusion that dopamine modulates neurogenesis in hippocampus, mainly via D receptors. [ABSTRACT FROM AUTHOR]

Our previous study together with other investigations have reported that neonatal hypoxia or ischemia induces long-term cognitive impairment, at least in part through brain inflammation and hypomyelination. However, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 (P0) rat pups to systemic hypoxia (3.5 h). We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP analogue 2′,3′-0-(2,4,6-trinitrophenyl)-adenosine 5′-triphosphate (TNP-ATP; blocks all ionotropic P2X1-7 receptors), whereas treatment with pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; inhibits P2X1-3 and P2X5-7 receptors) was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be partially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dysfunction after neonatal hypoxia. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to estimate the association between time from uterine incision to delivery and hypoxic neonatal outcomes in nonanomalous term infants. Methods All women undergoing in-labor term cesarean deliveries (CDs) in the first 2 years of an ongoing prospective cohort study were included. The primary exposure was time in seconds from uterine incision to delivery. The primary outcome was a composite of hypoxia-associated neonatal outcomes, defined as at least one of: seizures, hypoxic ischemic encephalopathy, need for hypothermia treatment, and death within 7 days. Results Of 812 patients who underwent in-labor CD, the composite hypoxia outcome occurred in 18 (2.2%) neonates. There was no significantdifference in the rateofhypoxic morbidity with increasing increments of 60 seconds from uterine incision to delivery (p = 0.35). There was a significantly increased risk of hypoxic morbidity in those delivered in the highest quintile (>240 seconds) compared with those in the lowest quintile (≤60 seconds) in cesareans performed for an indication other than nonreassuring fetal status (relative risk, 5.58; 95% confidence interval, 1.30-23.91). Conclusion Overall, duration from uterine incision to delivery for in-labor cesareans of nonanomalous term infants was not associated with an increase in risk of hypoxia-associated morbidities. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

As a consequence of obstetric complications, neonatal hypoxia has been discussed as an environmental factor in the pathophysiology of schizophrenia. However, the biological consequences of hypoxia are unclear. The neurodevelopmental hypothesis of schizophrenia suggests that the onset of abnormal brain development and neuropathology occurs perinatally, whereas symptoms of the disease appear in early adulthood. In our animal model of chronic neonatal hypoxia, we have detected behavioral alterations resembling those known from schizophrenia. Disturbances in cell proliferation possibly contribute to the pathophysiology of this disease. In the present study, we used postnatal rats to investigate cell proliferation in several brain areas following neonatal hypoxia. Rats were repeatedly exposed to hypoxia (89 % N, 11 % O) from postnatal day (PD) 4-8. We then evaluated cell proliferation on PD 13 and 39, respectively. These investigations were performed in the anterior cingulate cortex (ACC), caudate-putamen (CPU), dentate gyrus, and subventricular zone. Rats exposed to hypoxia exhibited increased cell proliferation in the ACC at PD 13, normalizing at PD 39. In other brain regions, no alterations have been detected. Additionally, hypoxia-treated rats showed decreased CPU volume at PD 13. The results of the present study on the one hand support the assumption of chronic hypoxia influencing transient cell proliferation in the ACC, and on the other hand reveal normalization during ageing. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to describe and evaluate an experimental model of neonatal normocapnic hypoxia and resuscitation. Methods: Ten male Landrace/Large White neonatal piglets were studied. Following anaesthesia and intubation, the animals were mechanically ventilated. Surgical procedures included catheterization of the right internal jugular vein and the carotid artery. After stabilization with 21% O2, normocapnic hypoxia was induced by decreasing the inspired O2 to 6-8%. When piglets developed bradycardia (heart rate < 60 beats/min), reoxygenation was initiated by administering 21% O2. Arterial blood samples were taken during baseline, hypoxia and reoxygenation in order to measure interleukine-6 and interleukine-8. Results: Nine out of ten animals were successfully resuscitated (one of these required chest compressions and a dose of adrenaline) and one died despite resuscitation efforts. After returning to baseline haemodynamic values, euthanasia was performed using thiopental overdose. Conclusions: Haemodynamic fluctuations at baseline, during normocapnic hypoxia and reoxygenation in Landrace/Large White piglets are comparable to that in human neonates, making the breed a favorable model of human neonatal hypoxia investigation. [ABSTRACT FROM AUTHOR]

Hypoxia in neonates disrupts the oxygen flow to the brain, essentially starving the brain and preventing it from performing vital biochemical processes important for central nervous system development. Hypoxia results in a permanent brain damage by gene and receptor level alterations mediated through neurotransmitters. The present study evaluated GABA, GABAA, GABAB receptor functions and gene expression changes in glutamate decarboxylase in the corpus striatum of hypoxic neonatal rats and the treatment groups with glucose, oxygen and epinephrine. Since GABA is the principal neurotransmitter involved in hypoxic ventilatory decline, the alterations in its level under hypoxic stress points to an important aspect of respiratory control. Following hypoxic stress, a significant decrease in total GABA, GABAA and GABAB receptors function and GAD expression was observed in the striatum, which accounts for the ventilator decline. Hypoxic rats treated with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GAD to near control. Being a source of immediate energy, glucose can reduce the ATP-depletion-induced changes in GABA and oxygenation helps in overcoming reduction in oxygen supply. Treatment with oxygen alone and epinephrine was not effective in reversing the altered receptor functions. Thus, our study point to the functional role of GABA receptors in mediating ventilatory response to hypoxia and the neuroprotective role of glucose treatment. This has immense significance in the proper management of neonatal hypoxia for a better intellect in the later stages of life. [ABSTRACT FROM AUTHOR]

Responses of the endocrine system are vital in revealing the mechanisms of respiratory activities. The present study focused on changes in insulin and triiodothyronine concentration in serum, its receptors in the hearts of hypoxic neonatal rats and glucose, oxygen, and epinephrine resuscitated groups. The insulin concentration was significantly increased with a significant upregulation of receptors in hypoxic neonates. Triiodothyronine content and its receptors were significantly decreased in serum and the hearts of hypoxic neonates. The change in hormonal levels is an adaptive modification of the endocrine system to encounter the stress. The effectiveness of glucose resuscitation to hypoxic neonates was also reported. [ABSTRACT FROM AUTHOR]

Background-:Hypoxia during the first week of life can induce neuronal death in vulnerable brain regions usuallyassociated with an impairment of cognitive function that can be detected later in life. The neurobiological changesmediated through neurotransmitters and other signaling molecules associated with neonatal hypoxia are animportant aspect in establishing a proper neonatal care.Methods-:The present study evaluated total GABA, GABAB receptor alterations, gene expression changes in GABAB receptor and glutamate decarboxylase in the cerebellum and brain stem of hypoxic neonatal rats and theresuscitation groups with glucose, oxygen and epinephrine. Radiolabelled GABA and baclofen were used forreceptor studies of GABA and GABABreceptors respectively and Real Time PCR analysis using specific probes forGABAB receptor and GAD mRNA was done for gene expression studies.Results-:The adaptive response of the body to hypoxic stress resulted in a reduction in total GABA and GABAB receptors along with decreased Breceptor and GAD gene expression in the cerebellum and brain stem.Hypoxic rats supplemented with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GAD. Resuscitation with oxygen alone and epinephrine was less effective in reversing the receptoralterations.Conclusions-:Being a source of immediate energy, glucose can reduce the ATP-depletion-induced changes inGABA and oxygenation, which helps in encountering hypoxia. The present study suggests that reduction in theGABABreceptors functional regulation during hypoxia plays an important role in central nervous system damage.Resuscitation with glucose alone and glucose and oxygen to hypoxic neonatal rats helps in protecting the brainfrom severe hypoxic damage. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O2; nHx group) in a sealed chamber, or to normoxia (21% O2; nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O2. Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO2) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude. [ABSTRACT FROM AUTHOR]

Several independent lines of evidence suggest mitochondrial dysfunction in schizophrenia in brain and periphery, including mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system, and altered mitochondrial-related gene expression. In an attempt to decipher whether mitochondrial complex I abnormality in schizophrenia is a core pathophysiological process or is attributable to medication, we studied two animal models of schizophrenia related to the neurodevelopmental hypothesis of this disorder. Protein levels of complex I subunits, 24, 51, and 75 kDa, were assessed in neonatal ventral hippocampal lesion rat model and in rats exposed to hypoxia at a neonatal age. In the prefrontal cortex, a major anatomical substrate of schizophrenia, neonatal ventral hippocampal lesion induced a significant prepubertal increase and postpubertal decrease in all three subunits of complex I as compared to sham-treated rats, while no change was observed in the cingulate cortex. Neonatal exposure to hypoxia did not affect protein levels of any of the three subunits in the prefrontal cortex. An age-dependent increase in the expression of complex I subunits was observed, which was distorted in the prefrontal cortex by the neonatal ventral hippocampal lesion. Complex I alterations in schizophrenia-related neurodevelopmental rat models appear to be brain region and animal model dependent. The results of this study support previous findings suggesting abnormal complex I expression as a pathological characteristic of schizophrenia rather than an effect of medication. [ABSTRACT FROM AUTHOR]

Purpose: To determine if posthypoxia treatment with erythropoietin (EPO) has protective effects against subsequent susceptibility to seizure related neuronal injury in rat pups subjected to acute hypoxia at P10. Methods: Four groups of rats were manipulated at P10, as described below, then all received kainic acid (KA) (10 mg/kg i.p.) at P29: Hypoxia-NS-KA group (n = 11): subjected to acute hypoxia (down to 4% O2), and then immediately received saline i.p. Hypoxia-EPO-KA group (n = 10): subjected to acute hypoxia and then immediately received EPO (1,000 U/Kg i.p.). Normoxia-NS-KA group (n = 11): sham manipulated and injected with saline. Normoxia-EPO-KA group (n = 10): sham manipulated then immediately injected with EPO (1000 U/Kg i.p.). After receiving KA at P29, all rats were monitored using videotape techniques, and were sacrificed at P31. TUNEL and Hoechst stains to assess for apoptosis, and regular histology for hippocampal cell counts were performed. Results: Administration of the single dose of erythropoietin directly after an acute hypoxic event at P10 resulted at P29 in increased latency to forelimb clonus seizures, reduced duration of these seizures, protection against hippocampal cell loss, and decreased hippocampal apoptosis in the Hypoxia-EPO-KA group as compared to the Hypoxia-NS-KA group. Conclusion: These data support the presence of favorable protective effects of erythropoietin against the long-term consequences of acute hypoxia in the developing brain and raise the possibility of its investigation as a potential neuroprotective agent after human neonatal hypoxic encephalopathy. [ABSTRACT FROM AUTHOR]

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1. In the present work we describe the short term effects of mild neonatal hypoxia on the synapse as assessed by the immunoreactivity (IR) of twosynaptic proteins: rab 3A and synaptobrevin (VAMP). 2. Using the sensitive methodology of immunoblotting, we measured rab 3A andVAMP-IR in homogenates from the cerebral cortex, hippocampus, and corpus striatum of control (breathing room air) and hypoxiated (breathing 95.5% N2–6.5% O2 for 70 min) 4-day-old rats at 1, 2, and 6 h after the end of the hypoxia. Immunostaining with examination by light microscopy was performed using the synaptic protein-specific antibodies on fixed brain sections from animals belonging to the same litter and submitted to hypoxia. 3. A transient increase of VAMP-IR was observed in the hippocampus and corpus striatum, and for rab 3A in the striatum, 1 h after initiating reoxygenation.At the following time points the values returned to control levels. This effectwas less clearly observed in the immunostained sections. 4. Mild hypoxia has an effect on sensitive brain regions, eliciting an increase in the IR of at least two proteins involved in the synaptic vesicle cycle. The transient nature of this effect possibly indicates the activation of endogenous neuroprotective mechanisms. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Perinatal Asphyxia (PA) is a leading cause of motor and neuropsychiatric disability associated with sustained oxidative stress, neuroinflammation, and cell death, affecting brain development. Based on a rat model of global PA, we investigated the neuroprotective effect of intranasally administered secretome, derived from human adipose mesenchymal stem cells (MSC-S), preconditioned with either deferoxamine (an hypoxia-mimetic) or TNF-α+IFN-γ (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 °C for 21 min. Thereafter, 16 μL of MSC-S (containing 6 μg of protein derived from 2 × 105 preconditioned-MSC), or vehicle, were intranasally administered 2 h after birth to asphyxia-exposed and control rats, evaluated at postnatal day (P) 7. Alternatively, pups received a dose of either preconditioned MSC-S or vehicle, both at 2 h and P7, and were evaluated at P14, P30, and P60. The preconditioned MSC-S treatment (i) reversed asphyxia-induced oxidative stress in the hippocampus (oxidized/reduced glutathione); (ii) increased antioxidative Nuclear Erythroid 2-Related Factor 2 (NRF2) translocation; (iii) increased NQO1 antioxidant protein; (iv) reduced neuroinflammation (decreasing nuclearNF-κB/p65 levels and microglial reactivity); (v) decreased cleaved-caspase-3 cell-death; (vi) improved righting reflex, negative geotaxis, cliff aversion, locomotor activity, anxiety, motor coordination, and recognition memory. Overall, the study demonstrates that intranasal administration of preconditioned MSC-S is a novel therapeutic strategy that prevents the long-term effects of perinatal asphyxia. [ABSTRACT FROM AUTHOR]

The topic of neonatal hypoxia is of paramount importance to anyone who cares during pregnancy and childbirth. Modern medicine associates this pathology with severe problems in the prenatal period. Underlying diseases of the mother during pregnancy, her anamnesis of life are the leading causes of complications in the newborn. Nevertheless, patterns of fetal hypoxia and neonatal hypoxia, as well as mechanisms of hypoxic-ischemic encephalopathy in newborns, remains poorly known and require further research. This study is focused on finding risk factors related to the chronic fetal hypoxia and defining a group of signs for diagnosing neonatal hypoxia. The real data of 186 pregnant women at the gestation age from 12 to 38 weeks were analyzed. A methodology for discovering interesting associations in gestation course data is proposed. Technique for association rules mining and rules selection by the neonatal hypoxia under study is discussed. The rules suggest that a strong relationship exists between the specific sets of attributes and the diagnosis. As a result, we set up a profile of the pregnant woman with a high likelihood of hypoxia of the newborn that would be beneficial to medical professionals. [ABSTRACT FROM AUTHOR]