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Abstract: We investigated whether the effect of neonatal hypoxia on amphetamine-induced hyperlocomotion can reproduce the ontogenic (age of onset) properties of schizophrenia. Neonatal hypoxia enhanced amphetamine-induced hyperlocomotion in adult mice and decreased it in adolescent mice. These findings provide ontogenic validity for this very simple animal model of schizophrenia. [Copyright &y& Elsevier]

Abstract: Cholinergic system is important for respiratory control from the first days of life. Disturbances in cholinergic pathway due to early life stress like hypoxic shock can adversely affect the ventilatory response. The present study evaluates neonatal hypoxic insult mediated cholinergic disturbances and the role of glucose, oxygen and epinephrine resuscitation. The changes in total muscarinic, muscarinic M1, M2, M3 receptors and the enzymes involved in acetylcholine metabolism – cholineacetyl transferase and acetylcholine easterase in the cerebellum were analyzed. Hypoxic stress decreased cerebellar muscarinic receptor density with a decreased muscarinic M1, M2 and M3 receptor gene expression. The metabolic shift in the acetylcholine synthesis and release is indicated by the decreased cholineacetyl transferase mRNA expression and increased acetylcholine esterase gene expression. Glucose, acting as a precursor for acetyl choline synthesis and an immediate energy source, helps in reversing the cholinergic disturbances in hypoxic neonates. The limitation of immediate oxygenation and epinephrine administration in ameliorating cholinergic disturbances in hypoxic neonates was also reported. This will help in devising a better resuscitation program for the management of neonatal hypoxia. [Copyright &y& Elsevier]

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]

Abstract: Hypoxia in neonates causes dysfunction of excitatory and inhibitory neurotransmission resulting in permanent brain damage. The present study is to understand the cerebellar GABAA receptor alterations and neuroprotective effect of glucose supplementation prior to current sequence of resuscitation – oxygen and epinephrine supplementation in hypoxic neonatal rats. Hypoxic insult caused a significant decrease in GABAA receptor number along with down regulated expression of GABAAα1, GABAAα5, GABAAδ and GABAAγ3 receptor subunits in the cerebellum which accounts for the respiratory inhibition. Hypoxic rats supplemented with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GABAA receptor subunits expression to near control. Glucose can reduce ATP-depletion-induced alterations in GABA receptors, thereby assisting in overcoming the neuronal damage caused by hypoxia. Resuscitation with oxygen alone and epinephrine was less effective in reversing the receptor alterations. The reduction in the GABAA receptors functional regulation during hypoxia plays an important role in cerebellar damage. Resuscitation with glucose alone and glucose with oxygenation to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage. [Copyright &y& Elsevier]

Abstract: Background: There is a growing population of adults with repaired cyanotic congenital heart disease. These patients have increased risk of impaired cardiac health and premature death. We hypothesized that hypoxia in early life before surgical intervention causes lasting changes in left ventricular structure and function with physiological implications in later life. Methods: Sprague–Dawley rats reared initially hypoxic conditions (FiO2 =0.12) for days 1–10 of life were compared to rats reared only in ambient air. Cellular morphology and viability were compared among LV cardiomyocytes and histological analyses were performed on LV myocardium and arterioles. Intracellular calcium transients and cell shortening were measured in freshly-isolated cardiomyocytes, and mitochondrial hexokinase 2 (HK2) expression and activity were determined. Transthoracic echocardiography was used to assess LV function in anesthetized animals. Results: Cardiomyocytes from adult animals following hypoxia in early life had greater cellular volumes but significantly reduced viability. Echocardiographic analyses revealed LV hypertrophy and diastolic dysfunction, and alterations in cardiomyocyte calcium transients and cell shortening suggested impaired diastolic calcium reuptake. Histological analyses revealed significantly greater intima–media thickness and decreased lumen area in LV arterioles from hypoxic animals. Alterations in mitochondrial HK2 protein distribution and activity were also observed which may contribute to cardiomyocyte fragility. Conclusions: Hypoxia in early life causes lasting changes in left ventricular structure and function that may negatively influence myocardial and vascular responses to physiological stress in later life. These data have implications for the growing population of adults with repaired or palliated cyanotic congenital heart disease. [Copyright &y& Elsevier]

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]

Abstract: Alterations in neurotransmitters and its receptors expression induce brain injury during neonatal hypoxic insult. Molecular processes regulating the serotonergic receptors play an important role in the control of respiration under hypoxic insult. The present study focused on the serotonergic regulation of neonatal hypoxia and its resuscitation methods. Receptor binding assays and gene expression studies were done to evaluate the changes in 5HT2A receptors and its transporter in the corpus striatum of hypoxic neonatal rats and hypoxic rats resuscitated with glucose, oxygen and epinephrine. Total 5HT and 5HT2A receptor number was increased in hypoxic neonates along with an up regulation of 5HT2A receptor and 5HT transporter gene. The enhanced striatal 5HT2A receptors modulate the ventilatory response to hypoxia. Immediate glucose resuscitation was found to ameliorate the receptor and transporter alterations. Hypoxia induced ATP depletion mediated reduction in blood glucose levels can be encountered by glucose administration and oxygenation helps in overcoming the anaerobic condition. The adverse effect of immediate oxygenation and epinephrine supplementation was also reported. This has immense clinical significance in establishing a proper resuscitation for the management of neonatal hypoxia. [Copyright &y& Elsevier]

Purpose: This study was undertaken to assess the relationship between the degree of meconium staining of the extraplacental membranes at birth, meconium aspiration, and pulmonary changes in neonates and stillbirth. Methods: The lungs, extraplacental membranes and placenta from 20 stillborn with meconium-stained membranes and 13 lungs of perinatal deaths were collected and microscopically examined for meconium, intra-alveolar presence of aspiration and inflammation. Results: Microscopically, 32% and 40% of the lungs had evidence of meconium for the stained and nonstained groups, respectively. The microscopic grade of meconium aspiration and inflammatory cells was not different between nonstained and meconium-stained membranes. Aspiration of meconium induced a granulomatous response in the lungs. Conclusion: It was concluded that the grade of meconium staining is a good indicator of fetal hypoxia, but not a good predictor for meconium aspiration and MAS in newborn. [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]

Although recent studies have documented compensatory generation of neurons in adult brains in response to various insults, a noninjurious short episode of hypoxia in rat neonates has been shown to trigger neurogenesis within the ensuing weeks, without apparent brain lesions. Very little is known of the long-term consequences. We therefore investigated the effects of such a conditioning-like hypoxia (100% N2, 5 min) on the brain and the cognitive outcomes of rats at 40 to 100 days of age. Control and posthypoxic rats developed similar learning capacities over postnatal days 14 to 18, but hypoxia was associated with enhanced scores in a test used to evaluate memory retrieval between 40 and 100 days. A striking sexual dimorphism was observed, with an earlier functional gain observed in female (40 days) compared with male (100 days) rats; gains were associated with matching structural changes in areas involved in cognition, including the hippocampus and frontal cortex. Therefore, it is proposed that brief neonatal hypoxia may exert long-term beneficial effects through neurogenesis stimulation. [Copyright &y& Elsevier]

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]

Abstract: Gestational deficiency in methyl donors such as folate and vitamin B12 impairs homocysteine metabolism and can alter brain development in the progeny. Since short hypoxia has been shown to be neuroprotective in preconditioning studies, we aimed to investigate the effects of brief, non-lesioning neonatal hypoxia (100% N2 for 5 min) on the developing brain of rats born to dams fed either a standard diet or a diet lacking vitamins B12, B2, folate and choline until offspring''s weaning. While having no influence on brain accumulation of homocysteine and concomitant apoptosis in 21-day-old deficient pups, exposure to hypoxia reduced morphological injury of the hippocampal CA1 layer. It also markedly stimulated the incorporation of bromodeoxyuridine (BrdU) in permissive areas such as the subventricular zone and the hippocampus followed by the migration of new neurons. Scores in a locomotor coordination test (days 19–21) and learning and memory behavior in the eight-arm maze (days 80–84) were found to be significantly improved in rats exposed to hypoxia in addition to the deficient diet. Therefore, by stimulating neurogenesis in rat pups, brief neonatal hypoxia appeared to attenuate the long-term effects of early exposure to a deficiency in nutritional determinants of hyperhomocysteinemia. [Copyright &y& Elsevier]

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]

Chloride (Cl–) efflux induces depolarization and contraction of vascular smooth muscle cells. In the basilar arteries from the New Zealand white rabbits, the role of Cl– flux in serotonin-induced contraction was demonstrated by (i) inhibition of Na+-K+-2Cl– co-transporter (NKCC1) to decreased Cl– influx with bumetanide; (ii) a disabled Cl–/HCO3– exchanger with bicarbonate free HEPES solution; (iii) blockade of Cl– channels using 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and indanyloxyacetic acid 94, R-(+)-methylindazone (R-(+)-IAA-94); and (iv) substitution of extracellular Cl– with methanesulfonate acid (113 mmol/L; Cl–, 10 mmol/L). In addition, the expression of NKCC1 in brain tissues after neonatal hypoxia-ischemia was examined at mRNA and protein levels using RT-PCR and Western blotting techniques. NKCC1 mRNA and protein expressions were increased at 24 and 48 h and returned to normal levels at 72 h after hypoxia insult when compared with the control littermates. In conclusion, Cl– efflux regulates cerebral circulation and the up-regulation of NKCC1 after neonatal hypoxia-ischemia may contribute to brain injury. [ABSTRACT FROM AUTHOR]

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]

The authors hypothesize that particularly severely compromised and asphyctic term infants in need of resuscitation may benefit from delayed umbilical cord clamping (after several minutes). Although evidence is sparse, the underlying pathophysiological mechanisms support this assumption. For this review the authors have analyzed the available research. Based on these data they conclude that it may be unfavorable to immediately clamp the cord of asphyctic newborns (e.g., after shoulder dystocia) although recommended in current guidelines to provide quick neonatological support. Compression of the umbilical cord or thorax obstructs venous flow to the fetus more than arterial flow to the placenta. The fetus is consequently cut off from a supply of oxygenated, venous blood. This may cause not only hypoxemia and consecutive hypoxia during delivery but possibly also hypovolemia. Immediate cord clamping may aggravate the situation of the already compromised newborn, particularly if the cord is cut before the lungs are ventilated. By contrast, delayed cord clamping leads to fetoplacental transfusion of oxygenated venous blood, which may buffer an existing acidosis. Furthermore, it may enhance blood volume by up to 20%, leading to higher levels of various blood components, such as red and white blood cells, thrombocytes, mesenchymal stem cells, immunoglobulins, and iron. In addition, the resulting increase in pulmonary perfusion may compensate for an existing hypoxemia or hypoxia. Early cord clamping before lung perfusion reduces the preload of the left ventricle and hinders the establishment of sufficient circulation. Animal models and clinical trials support this opinion. The authors raise the question whether it would be better to resuscitate compromised newborns with intact umbilical cords. Obstetric and neonatal teams need to work even closer together to improve neonatal outcomes., Competing Interests: Conflict of Interest/Interessenkonflikt Maul: Expert consultant for PeriZert, expert consultant for insurance companies (Ecclesia, Interschaden) and various medical associations, mediation bodies, and courts; lectures for GE Medical, Milupa, Cook Medical, ITF Pharma, CSL Behring; congress organizer for WfM Ultraschall, Buxtehude, and congress organization for Jörg Eickeler, Düsseldorf; Functions: vice-president and regional chairman for Hamburg, Association of Leading Hospital Clinicians (VLK), Düsseldorf; chairman of the North German Society for Gynecology and Obstetrics. Ott: None. Kyvernitakis: None. Kribs: Speakerʼs fees from Chiesi, Medela, Vygon, Infektopharm. Berger: Milupa. Ehlen: None. Schmidtke: None. Rawnaq-Möllers: None. Patrick Stelzl has a part-time job agreement as consultant and speaker and is member of the Steering Committee in concerns of the LION (“Labour Induction Outcomes Network”) project for Angusta 25 μg tablets from Norgine Pharma GmbH. Rath: Lectures for CSL Behring, Nette, Ferring/ Maul: Fachgutachter für PeriZert, Fachgutachter für Versicherungen (Ecclesia, Interschaden) und verschiedene Ärztekammern, Schlichtungsstellen und Gerichte, Vorträge für GE Medical, Milupa, Cook Medical, ITF Pharma, CSL Behring; Kongressorganisator für WfM Ultraschall, Buxtehude, und Kongressorganisation Jörg Eickeler, Düsseldorf; Ämter: Vizepräsident und Landesvorsitzender Hamburg, Verband Leitender Krankenhausärzte (VLK), Düsseldorf, Vorsitzender der Norddeutschen Gesellschaft für Gynäkologie und Geburtshilfe. Ott: Keine. Kyvernitakis: Keine. Kribs: Vortragshonorare von Chiesi, Medela, Vygon, Infektopharm. Berger: Milupa. Ehlen: Keine. Schmidtke: Keine. Rawnaq-Möllers: Keine. Patrick Stelzl hat einen Teilzeitarbeitsvertrag als Berater und Sprecher und ist Mitglied des Steuerungskomitees für Belange des LION-(„Labour Induction Outcomes Network“-)Projekts im Zusammenhang mit Angusta 25 μg Tablettes von Norgine Pharma GmbH. Rath: Vorträge für CSL Behring, Nette, Ferring., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective: More women are obese at their first prenatal visit and then subsequently gain further weight throughout pregnancy than ever before. The impact on the infant's development of neonatal hypoxic ischemic encephalopathy (HIE) has not been well studied. Using defined physiologic and neurologic criteria, our primary aim was to determine if maternal obesity conferred an additional risk of HIE., Study Design: Data from the New York State Perinatal Data System of all singleton, term births in the Northeastern New York region were reviewed using the NIH obesity definition (Body Mass Index (BMI) ≥ 30 kg/m2). Neurologic and physiologic parameters were used to make the diagnosis of HIE. Physiologic criteria included the presence of an acute perinatal event, 10-min Apgar score ≤ 5, and metabolic acidosis. Neurologic factors included hypotonia, abnormal reflexes, absent or weak suck, hyperalert, or irritable state or evidence of clinical seizures. Therapeutic hypothermia was initiated if the infant met HIE criteria when assessed by the medical team. Logistic regression analysis was used to assess the effect of maternal body mass index on the diagnosis of HIE., Results: In this large retrospective cohort study we evaluated outcomes of 97,488 pregnancies. Infants born to obese mothers were more likely to require ventilatory assistance and have a lower 5-min Apgar score. After adjusting for type of delivery and maternal risk factors, infants of obese mothers were diagnosed with HIE more frequently than infants of non-obese mothers, OR 1.96 (1.33-2.89) ( p = 0.001)., Conclusion: Infants of obese mothers were significantly more likely to have the diagnosis of HIE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Monaco-Brown, Munshi, Horgan, Gifford and Khalak.)

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Abstract Background- Hypoxia during the first week of life can induce neuronal death in vulnerable brain regions usually associated with an impairment of cognitive function that can be detected later in life. The neurobiological changes mediated through neurotransmitters and other signaling molecules associated with neonatal hypoxia are an important 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 the resuscitation groups with glucose, oxygen and epinephrine. Radiolabelled GABA and baclofen were used for receptor studies of GABA and GABAB receptors respectively and Real Time PCR analysis using specific probes for GABAB 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 GABAB receptor 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 receptor alterations. Conclusions- Being a source of immediate energy, glucose can reduce the ATP-depletion-induced changes in GABA and oxygenation, which helps in encountering hypoxia. The present study suggests that reduction in the GABAB receptors 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 brain from severe hypoxic damage.