RORα (Retinoic acid receptor related Orphan Receptor α) est un récepteur nucléaire<br />dont la perte de fonction entraîne chez la souris staggerer - entre autres phénotypes - une<br />sévère ataxie cérébelleuse. RORα a longtemps été considéré comme un récepteur nucléaire<br />orphelin, cependant, le cholestérol (ou un de ses dérivés) semble être un ligand physiologique<br />de ce récepteur.<br />Le mutant staggerer, identifié dès 1962 par Sidman, Lane et Dickie, présente une<br />hypoplasie cérébelleuse liée à l'absence de la grande majorité des cellules de Purkinje, ainsi<br />que des grains du cervelet. L'expression de la mutation staggerer dans les cellules de Purkinje<br />conduit à leur mort massive pendant le développement, et les cellules de Purkinje survivantes<br />chez l'adulte présentent d'importantes anomalies de différenciation. Par ailleurs, à l'état<br />hétérozygote, le mutant staggerer présente une diminution de la survie des cellules de<br />Purkinje ainsi que des anomalies de différenciation au cours du vieillissement.<br />Le phénotype cérébelleux des mutants homozygote et hétérozygote staggerer<br />suggère que RORα est impliqué dans la survie et/ou la différenciation des cellules de Purkinje<br />au cours du développement et du vieillissement. Au cours de cette thèse, nous avons donc<br />tenté de déterminer le rôle de RORα dans la survie et la différenciation dans des neurones<br />corticaux et/ou dans des cellules de Purkinje, en étudiant l'effet de sa surexpression dans ces<br />processus.<br />Afin de surexprimer RORα, nous avons construit un vecteur lentiviral exprimant<br />l'isoforme humaine RORα1. Ce vecteur nous a permis de transduire avec une très grande<br />efficacité des neurones corticaux en culture primaire ainsi que les cellules de Purkinje en<br />culture organotypique.<br />Dans une première étude, nous avons cherché à déterminer si RORα pouvait exercer<br />un rôle dans la survie neuronale. Dans ce but, nous avons évalué la survie de neurones<br />corticaux surexprimant ou non RORα et soumis à un stress oxydatif entraînant l'apoptose des<br />neurones. RORα protège les neurones en diminuant le stress oxydatif causé par ces inducteurs<br />pro-apoptotiques. L'expression des deux enzymes Glutathion peroxydase 1 et Peroxiredoxine<br />6 est augmentée dans les neurones qui surexpriment hRORα1, et semble partiellement médier<br />l'effet neuroprotecteur de RORα. Nous avons par ailleurs évalué et comparé la survie des<br />cellules de Purkinje en culture organotypique qui expriment RORα de façon endogène, ou qui<br />surexpriment hRORα1, et nos résultats suggèrent que la surexpression de RORα a également<br />un effet neuroprotecteur dans ces cellules.<br />Dans une seconde étude, afin de déterminer le rôle de RORα dans la différenciation<br />des cellules de Purkinje, nous avons analysé en culture la progression de la différenciation<br />dendritique précoce de cellules de Purkinje en fonction de l'expression de RORα. RORα est<br />crucial pour l'étape de régression des neurites des cellules de Purkinje au stade bipolaire<br />embryonnaire. Alors que l'absence de RORα chez les mutants homozygotes staggerer<br />entraîne un arrêt de la différenciation des cellules de Purkinje à ce stade (les cellules de<br />Purkinje ne parviennent pas à entamer la régression des neurites), la surexpression de<br />hRORα1 accélère l'étape de régression. Cette étape de régression est totalement dépendantede l'expression de protéines RORα fonctionnelles et cet effet est vraisemblablementintrinsèque. Nous montrons enfin que l'hormone thyroïdienne accélère la différenciationdendritique précoce des cellules de Purkinje, et que RORα semble contribuer à ce processus.<br />L'ensemble de ces résultats montre que RORα intervient de façon cruciale à la foisdans la survie et dans la différenciation des cellules de Purkinje dans une étape très précoce de<br />leur développement post-natal.

Malgré sa complexité, le cerveau intègre en permanence de nouvelles cellules – à la fois neuronales et gliales – au-delà du développement embryonnaire et ce, tout le long de la vie. La période postnatale est caractérisée par une gliogenèse intense. A l’âge adulte, de nouveaux neurones et cellules gliales sont produits dans des régions restreintes à partir de cellules souches/progénitrices (CSP) localisées dans des niches. Les deux niches de CSP adultes les mieux décrites sont la zone sous-ventriculaire des ventricules latéraux, qui produit de nouveaux interneurones olfactifs, et la zone sous-granulaire du gyrus denté de l’hippocampe, où de nouveaux neurones en grain sont produits localement. Des travaux menés ces dernières années ont montré qu’une neuro- et une gliogenèse avaient aussi lieu dans l’hypothalamus postnatal, une petite région du diencéphale ventral qui régule des processus physiologiques vitaux tels que le métabolisme, la reproduction, le sommeil et la thermorégulation. Si l’identité des CSP hypothalamiques reste débattue, de nombreux travaux s’accordent sur l’importance de la neurogenèse hypothalamique postnatale dans le contrôle du métabolisme. Cependant, la possibilité que la genèse postnatale de cellules contribue aussi au contrôle de la fonction de reproduction, une autre fonction clé de l’hypothalamus, restait à explorer. L’objectif premier de mon travail de thèse était de rechercher si la genèse de cellules dans l’hypothalamus postnatal est impliquée dans le contrôle de la reproduction, une fonction physiologique qui requière un haut degré de plasticité. La fonction de reproduction est orchestrée par une petite population de neurones produisant la neurohormone Gonadotrophin-Releasing Hormone (GnRH). Ces neurones, qui naissent en dehors du cerveau, sont en place dans la région préoptique (RPO) de l’hypothalamus à la naissance. Cependant, ils doivent subir une maturation postnatale pour acquérir le profil de sécrétion qui leur permettra d’initier la puberté et d’assurer la fertilité de l’individu. Dans une première étude, grâce à une combinaison d’approches in vitro et in vivo, nous avons mis en évidence une vague d’astrogenèse dans l’environnement des neurones à GnRH au sein de la RPO au cours des deux premières semaines de vie postnatale chez la ratte. Nos résultats suggèrent que les neurones à GnRH utilisent la prostaglandine D2 pour attirer les progéniteurs environnants et que ce recrutement est important pour la maturation sexuelle. Dans une deuxième étude, nous avons recherché si de nouvelles cellules naissent à l’âge adulte dans des régions hypothalamiques qui contrôlent la fonction de reproduction. Nous montrons que des cellules sont produites dans la RPO chez la ratte adulte et que leur taux varie au cours du cycle oestral, suggérant une régulation par les stéroïdes sexuels. De plus, nous montrons que la survenue d’une gestation stimule la néogenèse cellulaire dans une zone de la RPO qui contrôle le comportement maternel. Si la néogenèse hypothalamique adulte a surtout été étudiée chez les rongeurs de laboratoire, il reste à déterminer si ce phénomène existe aussi chez l’homme. Pour aborder cette question, nous avons évalué dans une troisième étude l’expression de marqueurs de CSP dans l’hypothalamus humain adulte, comparativement au rongeur (souris, rat) et à un primate lémurien, le microcèbe. Nous montrons que l’hypothalamus humain adulte contient des populations de cellules au profil antigénique de CSP, dont certaines semblent propres à l’homme. Au total, ces travaux montrent que de nouvelles cellules naissent dans des régions hypothalamiques qui contrôlent la fonction de reproduction au cours de la vie postnatale et à l’âge adulte chez la ratte, et que ce phénomène est important pour la maturation sexuelle. L’observation de CSP putatives dans l’hypothalamus humain adulte suggère que la capacité de l’hypothalamus à produire de nouvelles cellules à l’âge adulte existe aussi dans notre espèce. / Despite its complexity, the brain keeps adding new cells – both neuronal and glial – beyond embryonic development and throughout life. The postnatal period is characterized by intense and widespread gliogenesis. During adulthood, both glio- and neurogenesis occur in restricted locations from stem/progenitor cells (NPC) residing in niches. The two best-described niches of adult NPC are the subventricular zone of the lateral ventricles, which provides new interneurons to the olfactory bulb, and the subgranular zone of the hippocampal dentate gyrus that locally produces new granule cells. The last decade has seen an accumulation of studies showing that neuro- and gliogenesis also occur in the postnatal hypothalamus, a small portion of the ventral forebrain surrounding the third ventricle that regulates essential physiological processes such as metabolism, reproduction, sleep and thermoregulation. Even though the identity of hypothalamic NPC remains a matter of debate, a growing body of evidence points to postnatal hypothalamic neurogenesis relevance for the control of metabolism. However, a possible contribution of postnatal hypothalamic cell generation to the central control of reproduction, another key function of the hypothalamus, remained to be explored.The main aim of my doctoral researches was to evaluate whether the generation of new cells in the postnatal hypothalamus contributes to the central control of reproduction, a physiological function known to require a high degree of plasticity. The reproductive function is controlled by a small population of neurons producing the neurohormone Gonadotrophin-Releasing Hormone (GnRH). These neurons, which are born in the nasal placodes, are in place at birth in the preoptic area (POA) of the hypothalamus. However, they need a postnatal maturation to reach a mature secretory pattern that will trigger puberty and subsequent fertility.In a first study, using a combination of in vitro and in vivo experiments, we showed that a wave of astrogenesis occurs in the POA from local progenitors in the environment of GnRH neurons during the first weeks of postnatal life in the female rat. We identified prostaglandin D2 as a factor used by GnRH neurons to attract progenitors in their vicinity and showed that impaired progenitor recruitment alters sexual maturation.In a second study, we evaluated whether cell neogenesis still occurs during adulthood in hypothalamic regions relevant for the reproductive function. Our results showed that new cells are born in the POA of adult female rats. The rate of cell neogenesis varies across the estrus cycle, suggesting a regulatory influence of gonadal steroids. Moreover, we showed that gestation impacts the rate of cell neogenesis in a POA region implicated in the control of maternal behavior.While cell neogenesis in the adult hypothalamus has been mainly studied in laboratory rodents, it remains to be known whether this phenomenon also occurs in humans. To start addressing this question, we evaluated in a third study the expression of a panel of NPC markers in the adult human hypothalamus and compared it to that found in rodents (mouse, rat) and a lemur primate, the grey mouse lemur. Our results showed that the adult human hypothalamus contains populations of cells with an antigenic profile of NPC, some of which appear specific to humans.Altogether, this work shows that new cells are born in hypothalamic regions controlling reproduction throughout postnatal and adult life in female rats, and that this process is required for sexual maturation. The identification of NPC marker-expressing cells in the adult human hypothalamus suggests that the capacity for cell neogenesis also exists in the hypothalamus of our species.

No / There is now a body of research evaluating breastfeeding interventions and exploring mothers' and health professionals' views on effective and ineffective breastfeeding support. However, this literature leaves relatively unexplored a number of questions about how breastfeeding women experience and make sense of their relationships with those trained to provide breastfeeding support. The present study collected qualitative data from 22 breastfeeding first-time mothers in the United Kingdom on their experiences of, and orientation towards, relationships with maternity care professionals and other breastfeeding advisors. The data were obtained from interviews and audio-diaries at two time points during the first 5 weeks post-partum. We discuss a key theme within the data of 'Making use of expertise' and three subthemes that capture the way in which the women's orientation towards those assumed to have breastfeeding expertise varied according to whether the women (1) adopted a position of consulting experts vs. one of deferring to feeding authorities; (2) experienced difficulty interpreting their own and their baby's bodies; and (3) experienced the expertise of health workers as empowering or disempowering. Although sometimes mothers felt empowered by aligning themselves with the scientific approach and 'normalising gaze' of health care professionals, at other times this gaze could be experienced as objectifying and diminishing. The merits and limitations of a person-centred approach to breastfeeding support are discussed in relation to using breastfeeding expertise in an empowering rather than disempowering way. / British Academy. Grant Number: 37524

O presente estudo analizou nove gânglios cervicais craniais esquerdos (GCC) de Cutias (Dasyprocta aguti) machos oriundos do criatório da Universidade Federal Rural do Semi Árido Nordestino de Mossoró- RN. Nestes animais foi estimado o número total dos neurônios (mono e binucleados), bem como seus volumes, volume do gânglio, a densidade neuronal e densidade de volume neuronal durante o desenvolvimento pós-natal (maturação): animais neonatos, jovens e adultos. Os GCCs foram fixados com solução de formoldeído (4%) em PBS, embebidos em solução de ágar e seccionados sistemática, uniforme e aleatoriamente para a aplicação dos métodos estereológicos entre os quais disector e rotator ópticos. para a estimativa da densidade e do volume neuronal, respectivamente. Houve diferença significativa entre os grupos etários para os parâmetros: volume ganglionar, número total de neurônios binucleados, volume neuronal médio de neuronios mono e binucleados e densidade de volume neuronal. A conclusão é de que a idade influencia quantitativamente a dinamica neuronal do GCC de cutias e futuramente estes dados servirão como base para a investigação da ocorrência de divisão celular durante o período pós-natal em roedores. / The present study was pursued in nine left cranial cervical ganglia (CCG) of male cutias (Dasyprocta aguti) obtained from the animal house of the Universidade Federal Rural do Semi-Árido Nordestina em Mossoró- RN. The number of CCG neurons as well as their volume, ganglion volume, numerical density and neuronal volume density were estimated during the post-natal development (maturation), in neonates, young and adult animals, by using 3-D design-based stereological methods, e.g., optical disector and optical rotator. Briefly, CCGs were fixed with a 4% formaldehyde solution in PBS, embedded in a 10% agar solution and exhaustively vibrosectioned (SURS) in order to accordingly perform the relevant stereological estimations. There were significant difference between age groups for the follow parameters: ganglion volume, total number of binucleated neurons, mean neuronal volume of mono and binucleated neurons and volume density of neurons. The conclusion is of that the age quantitative influences the dinamic of neuronal cells of the GCC of agoutis. In the future these data will serve as basis for the inquiry of the occurrence of cellular division during the post-natal period in rodents.

Childbirth can be associated with short and long-term psychological morbidity including depression, anxiety and trauma symptoms. Some previous studies have used psychological interventions to reduce postpartum distress but have primarily focussed on attempting to relieve symptoms of depression with little recognition of trauma symptoms. Furthermore, the intervention used in these studies has generally been poorly documented. The first aim of the present study was to develop a counselling framework, suitable for use by midwives, to address psychological trauma following childbirth. Multiple methods were used to develop the intervention including focus groups with women and midwives. Both the women and midwives gave unequivocal support for postpartum debriefing. Themes that emerged from the focus groups with women included the need for opportunities to talk about their birth experience, an explanation of events, an exploration of alternative courses of action that may have resulted in a different birth experience, talking about their feelings such as loss, fear, anger and self-blame, discussing social support, and discussing possible future childbearing. There was a high level of agreement between the women's and midwives' views. These themes were synthesized with contemporary literature describing counselling interventions to assist in reconciling a distressing birth experience and a model for understanding women's distressing birth experiences to develop a counselling framework. The counselling intervention was then tested using a randomised controlled study involving 400 women recruited from antenatal clinics of three public hospitals. When interviewed within seventy-two hours of birth, 103 women reported a distressing birth experience and were then randomised into either the treatment or control group. Women in the intervention group had the opportunity to debrief at the initial postpartum interview (< 72 hours postpartum) and at four to six weeks postpartum. The prevalence of posttraumatic stress disorder was quite high; 9.6% of participants meeting the diagnostic criteria for acute PTSD at four to six weeks postpartum. Fewer participants (3.5%) met the diagnostic criteria for chronic PTSD at three months postpartum. As with previous research relating to childbearing women, few demographic factors or antenatal psychological factors were associated with the development of a PTSD symptom profile following childbirth. The development of PTSD symptom profile was strongly associated with obstetric intervention and a perception of poor care in labour. This finding is also consistent with previous research. Emotional distress was reduced for women in the intervention group in relation to the number of PTSD symptoms [t (101) = 2.144, p = .035], depression [c2 (1) = 9.188, p = .002], stress [c2 (1) = 4.478, p = .029] and feelings of self-blame [t (101) = -12.424, p <.001]. Confidence about a future pregnancy was higher for these women [t (101) = -9.096, p <.001]. Although there was not a statistically significant difference in the number of women with a PTSD symptom profile at three months postpartum, fewer women in the intervention group (n=3) than in the control group (n=9) met PTSD criteria. Likewise, there were fewer women in the intervention group (n=1) with anxiety levels above mild than in the control group (n=6). Importantly, this study found that offering women who have had a traumatic birth the opportunity for counselling using the framework documented in this dissertation was not harmful. This finding is in contrast to previous findings of other studies. The intervention was well received by participants. All the women in the intervention group found the counselling sessions helped them come to terms with their birth experience. Maternity service providers need to be cognizant of the prevalence of this debilitating condition and be able to identify women at risk for early intervention and referral to a mental health practitioner if appropriate. This research offers further support for the compelling need to implement changes to the provision of maternity services that reduce rates of obstetric intervention and humanise service delivery as a means of primary prevention of birth-related PTSD.

Des changements dans le statut thyroïdien altèrent les fonctions testiculaires, impliquant, entre autre, le récepteur à la T3, TRα1. Lorsqu’un récepteur dominant-négatif de TRα1 (TRα AMI) est spécifiquement introduit dans les cellules de Sertoli (lignée TRα AMI-SC), on observe une augmentation significative de l’index de prolifération des cellules de Sertoli à 3 jpp, induisant une augmentation de la densité de ces cellules et du poids testiculaire chez l’adulte. Ce phénotype est corrélé à une modification de l’expression de gènes clés du cycle cellulaire dont Cdk4, JunD et c-myc. Lorsque le récepteur TRα AMI est introduit également dans les cellules de Leydig (lignée TRα AMI-Aro), la sécrétion de testostérone est augmentée. Enfin, nous montrons l’implication de l’isoforme mitochondriale p43 du récepteur TRα1, dans ce contrôle T3- dépendant et autonome de la prolifération des cellules de Sertoli suggérant l’existence d’un crosstalk entre génome nucléaire et mitochondrial dans cette régulation par la T3. / Changes in the thyroid status altered testicular functions, involving thyroid hormone receptors, among them, TRα1 is implied The expression of a TRα1 dominant-negative receptor (TRα AMI) specifically in Sertoli cells (TRα AMI-SC mice) leads to a significant increase in Sertoli cell proliferation at 3 dpp, inducing an increase in Sertoli cell density, testis weight and testicular spermatic reserve at adulthood. This phenotype is correlated with changes in cell cycle gene expression like Cdk4, JunD and c-myc. When TRα AMI is also expressed in Leydig cells (TRα AMI-Aro mice), it induces an increase in testosterone levels. Finally, we demonstrate that the mitochondrial p43 receptor is involved in this T3-dependant control of Sertoli cell proliferation, suggesting the existence of a crosstalk between nuclear and mitochondrial genomes.

O presente estudo analizou nove gânglios cervicais craniais esquerdos (GCC) de Cutias (Dasyprocta aguti) machos oriundos do criatório da Universidade Federal Rural do Semi Árido Nordestino de Mossoró- RN. Nestes animais foi estimado o número total dos neurônios (mono e binucleados), bem como seus volumes, volume do gânglio, a densidade neuronal e densidade de volume neuronal durante o desenvolvimento pós-natal (maturação): animais neonatos, jovens e adultos. Os GCCs foram fixados com solução de formoldeído (4%) em PBS, embebidos em solução de ágar e seccionados sistemática, uniforme e aleatoriamente para a aplicação dos métodos estereológicos entre os quais disector e rotator ópticos. para a estimativa da densidade e do volume neuronal, respectivamente. Houve diferença significativa entre os grupos etários para os parâmetros: volume ganglionar, número total de neurônios binucleados, volume neuronal médio de neuronios mono e binucleados e densidade de volume neuronal. A conclusão é de que a idade influencia quantitativamente a dinamica neuronal do GCC de cutias e futuramente estes dados servirão como base para a investigação da ocorrência de divisão celular durante o período pós-natal em roedores. / The present study was pursued in nine left cranial cervical ganglia (CCG) of male cutias (Dasyprocta aguti) obtained from the animal house of the Universidade Federal Rural do Semi-Árido Nordestina em Mossoró- RN. The number of CCG neurons as well as their volume, ganglion volume, numerical density and neuronal volume density were estimated during the post-natal development (maturation), in neonates, young and adult animals, by using 3-D design-based stereological methods, e.g., optical disector and optical rotator. Briefly, CCGs were fixed with a 4% formaldehyde solution in PBS, embedded in a 10% agar solution and exhaustively vibrosectioned (SURS) in order to accordingly perform the relevant stereological estimations. There were significant difference between age groups for the follow parameters: ganglion volume, total number of binucleated neurons, mean neuronal volume of mono and binucleated neurons and volume density of neurons. The conclusion is of that the age quantitative influences the dinamic of neuronal cells of the GCC of agoutis. In the future these data will serve as basis for the inquiry of the occurrence of cellular division during the post-natal period in rodents.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2015-01-16T19:26:27Z No. of bitstreams: 2 Dissertação - Marina Conceição dos Santos Moreira - 2014.pdf: 1731265 bytes, checksum: 317f0d1f433cdc033c1a41e2868132a4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Erika Demachki (erikademachki@gmail.com) on 2015-01-16T19:26:39Z (GMT) No. of bitstreams: 2 Dissertação - Marina Conceição dos Santos Moreira - 2014.pdf: 1731265 bytes, checksum: 317f0d1f433cdc033c1a41e2868132a4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-01-16T19:26:39Z (GMT). No. of bitstreams: 2 Dissertação - Marina Conceição dos Santos Moreira - 2014.pdf: 1731265 bytes, checksum: 317f0d1f433cdc033c1a41e2868132a4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Changes in plasma sodium concentration have led to adjustment mechanisms in order to restore their physiological conditions. The behavioral adjustments consist in the regulation of water and sodium intake. Among the vegetative adjustments, we highlight changes in renal sympathetic activity, blood pressure, renal blood flow (RBF) and renal vascular conductance (RVC). Experimental evidence has demonstrated increase of blo od pressure of the adult offspring from mothers with high sodium diets during pregnancy. Although these studies had demonstrated the importance of prenatal phases in hypertension development, there has been no evidence of the effects of high sodium diets during postnatal phases in relation to hypertension. Thus, in the present study, we evaluated the effects of sodium overload during childhood on cardiovascular and behavioral parameters in adulthood. That way, 21 days after birth, we have offered to the experimental group, hypertonic solution (NaCl 0.3 M) and food ad libitum for 60 days. The control rats were maintained with tap water and food ad libitum. Afterwards, both groups were maintained with tap water and food during 15 days (recovery). Later, we per formed chronic cannulation of right femoral artery to record baseline mean arterial pressure (MAP) and heart rate (HR) in unanesthetized animals. In the experimental group, we observed increases in basal MAP (118.3 ± 2.7 mmHg) and HR (398.2 ± 7.5 bpm), compared with the control group (98.6 ± 2.6 mmHg; 365.4 ± 12.2 bpm). Baroreflex index was diminished in experimental group in relation to control group by phenylephrine infusions ( -1.24 ± 0.2 bpm·mmHg -1 vs. -1.83 ± 0.04 bpm·mmHg -1 , respectively) as by sodium nitroprusside infusions (0.85 ± 0.22 bpm·mmHg -1 vs. 2.12 ± 0.2 bpm·mmHg -1 , respectively). The baseline values of MAP, HR, RBF, RVC and renal sympathetic nerve activity (RSNA) in anesthetized animals were evaluated. MAP and HR of experimental group (124.4 ± 3.0 mmHg; 437.9 ± 10.5 bpm) were significantly higher than control group (102.4 ± 2.4 mmHg; 375.2 ± 15.4 bpm). The baseline values of RBF (control: 3.4 ± 0.4 ml·min -1 ; experimental: 3.9 ± 0.2 ml·min -1 ), RVC (control: 0.0288 ± 0.0044 ml·(min·mmHg) -1 ; experimental: 0.0336 ± 0.0012 ml·(min·mmHg) -1 ) and RSNA (control: 0.0300 ± 0.0095 V and 89.5 ± 3.67 spikes·s -1 ; experimental: 0.0351 ± 0.0109 V and 78.1 ± 4.89 spikes·s -1 ) were similar between the groups. Ex vivo cardiovascular function in adulthood was also evaluated. It has been observed that animals treated with sodium overload during the postnatal period showed reduction of vascular endothelium-independent relaxation and also an increase in intraventricular diastolic pressure during the cardiac reperfusion. Furthermore, after the recovery period, the animals were submitted to osmotic challenge. The cardiovascular adjustments induced by acute hypernatremia were evaluated. It was observed that in the control animals, the infusion of hypertonic saline evoked a transient increase in MAP (Δ 9.2 ± 2.2 mmHg ), transient bradycardia (Δ -18.9 ± 7.9 bpm) and sustained increases in RBF (Δ 37.7 ± 6.9 % of baseline ) and RVC (Δ 50.0 ± 4.4 % of baseline, 60 min after infusion). However, in the experimental rats, hypertonic saline infusion caused a transient increase in MAP, higher than observed in control animals (Δ 18. 7 ± 1.7 mmHg, after 10 min) and sustained bradycardia (Δ -25.0 ± 10.2 bpm, after 60 min). The increases in RBF (Δ 30.8 ± 11.0% of baseline, after 60 min) and RVC (Δ 27.9 ± 12.3 % of baseline, af ter 60 min) were lower than the observed in the control group. Later, we performed tests of water and sodium intake induced by furosemide (10 mg·kg -1 bw, sc). In test-induced drinking, the hypertonic 0.3 M sodium intake was reduced in experimental animals compared to the control group (7.8 ± 1.1 ml vs. 12.1 ± 0.6 ml, respectively). Alt ogether, the results of the present study show that changes in hidromineral homeostasis, in postuterine phases, affect the behavioral and cardiovascular adjustments induced by sodium depletion and hypernatremia. Furthermore, they show that a high -sodium diet during the postnatal period alters baroreflex sensitivity and BP, in adulthood, compromising the cardiac relaxation after ischemia and endothelium-independent vasorelaxation . / Variações na concentração plasmática de sódio desencadeiam ajustes comportamentais e vegetativos que visam restabelecer as condições fisiológicas. Dentre estes ajustes, destacamos alterações do apetite ao sódio, da atividade simpática renal, da pressão arterial (PA), do fluxo sanguíneo renal (FSR) e da condutância vascular renal (CVR). Diversos estudos sugerem que doenças desenvolvidas na fase adulta estão relacionadas a certas condições às quais os indivíduos foram expostos dur ante os estágios iniciais da vida. Evidências experimentais têm demonstrado maior PA na prole adulta de mães alimentadas com dieta rica em sódio durante a gestação e a lactação. Apesar de demonstrarem a importância das fases pré-natais no desenvolvimento de hipertensão arterial, não existem evidências no que diz respeito aos efeitos de alterações do equilíbrio hidroeletrolítico durante as fases pós-natais em relação à hipertensão arterial. Assim, o presente trabalho avaliou os efeitos do aumento do consumo de sódio durante o período pós-natal sobre parâmetros cardiovasculares e comportamentais na fase adulta. Ratos Wistar com 21 dias de vida foram mantidos com solução salina hipertônica (NaCl 0,3 M) e ração ad libitum durante 60 dias (grupo experimental). Os animais do grupo controle foram mantidos com água e ração ad libitum. Após estes 60 dias, os animais de ambos os grupos foram mantidos com água e ração por um período de 15 dias (período de recuperação). Posteriormente, foi realizada canulação crônica da artéria e da veia femorais direitas para registro de pressão arterial média basal (PAM) e frequência cardíaca (FC) nos animais não anestesiados. No grupo experimental, observou-se aumentos na PAM (118,3 ± 2,7 mmHg) e na FC (398,2 ± 7,5 bpm) basais, quando comparado com o grupo controle (98,6 ± 2,6 mmHg; 365,4 ± 12,2 bpm). Além do mais, observamos uma diminuição no índice de barorreflexo nos animais experimentais quando comparados com o grupo controle, tanto para as infusões de fenilefrina (-1,24 ± 0,2 bpm·mmHg -1 vs. -1,83 ± 0,04 bpm·mmHg -1 , respectivamente), quanto para as infusões de nitroprussiato de sódio (0,85 ± 0,22 bpm·mmHg -1 vs. 2,12 ± 0,2 bpm·mmHg -1 , respectivamente). Os valores basais de PAM, FC, FSR, CVR e atividade nervosa simpática renal (ASR) nos animais anestesiados foram avaliados. A PAM e a FC do grupo experimental (124,4 ± 3,0 mmHg; 437,9 ± 10,5 bpm) foram significativamente maiores que do grupo controle (102,4 ± 2,4 mmHg; 375,2 ± 15,4 bpm). Os valores basais de FSR (controle: 3,4 ± 0,4 ml·min -1 ; experimental: 3,9 ± 0,2 ml·min -1 ), de CVR (controle: 28,8 ± 4,4 μl·(min·mmHg) -1 ; experimental: 33,6 ± 1,2 μl·(min·mmHg) -1 ) e ASR (controle: 0,0300 ± 0,0095 V e 89,5 ± 3,67 spikes·s -1 ; experimental: 0,0351 ± 0,0109 V e 78,1 ± 4,89 spikes·s -1 ) foram semelhantes entre os grupos . A função cardiovascular ex vivo na fase adulta também foi avaliada. Observou-se que os animais submetidos à sobrecarga de sódio durante o período pós-natal apresentaram comprometimento do relaxamento vascular independente de endotélio e ainda, aumento da pressão intraventricular diastólica durante o período de reperfusão cardíaca. Além disso, após o período de recuperação, os ajustes cardiovasculares induzidos por hipernatremia aguda foram avaliados. Observou -se que, nos animais controle, a infusão de salina hipertônica provocou aumento transitório de PAM (Δ9,2 ± 2,2 mmHg), bradicardia transitória (Δ -18,9 ± 7,9 bpm), além de aumentos sustentados do fluxo sanguíneo renal (Δ 37,7 ± 6,9% em relação ao basal, após 60 min) e da condutância vascular renal (Δ 50,0 ± 4,4% em relação ao basal; após 60 min). Já nos animais do grupo experimental, a infusão de salina hipertônica provocou aumento transitório de PAM, maior que o observado nos animais controle ( Δ 18,7 ± 1,7 mmHg, aos 10 min), e bradicardia sustentada (Δ -25,0 ± 10,2 bpm, após 60 min), além de aumentos de FSR (Δ 30,8 ± 11,0% em relação ao basal, após 60 min) e CVR (Δ 27,9 ± 12,3% em relação ao basal, após 60 min) menores que os observados no grupo controle. Após o período de recuperação, foram realizados testes de ingestão de água e sódio induzida por furosemida (10 mg · kg -1 peso corporal, s.c.). No teste de ingestão induzida, a ingestão de salina hipertônica 0,3 M se mostrou reduzida nos animais experimentais, quando comparados ao grupo controle (7,8 ± 1,1 ml vs. 12,1 ± 0,6 ml, respectivamente). Em conjunto, os resultados obtidos no presente trabalho demonstram que alterações na homeostase hidromineral na vida pós-uterina alteram os ajustes comportamentais e cardiovasculares induzidos por depleção de sódio e por infusão de salina hipertônica (NaCl 3 M). Além disso, demonstram que uma dieta rica em sódio durante o período pós natal altera a sensibilidade barorreflexa e a PA na fase adulta, além de comprometer o relaxamento cardíaco após isquemia e o vasorelaxamento independente de endotélio.

Introduction: Around 140 million children are born every year and post-natal transition is uncomplicated in the vast majority. However, around 5%–15% of neonates receive supportive interventions during transition. Recent data on the interventions used is scarce. More data on the frequencies with which these interventions are used is needed to evaluate neonatal resuscitation, guide recommendations and to generate hypotheses for further research. The following protocol describes an international, multicentre survey on the interventions currently applied during neonatal resuscitation. Objectives: To determine the frequencies at which different supportive interventions recommended by European Resuscitation Council (ERC) guidelines for neonatal resuscitation are used. To compare the frequencies between hospitals and patient groups and to investigate possible factors influencing any differences found. Methods: Participating hospitals will collect data on all interventions performed during neonatal resuscitation over a period of 6 months. All hospitals providing perinatal care are eligible regardless of size and designated level of neonatal care. Every neonate requiring more interventions than basic drying and tactile stimulation during the first 30 min of life will be included. The targeted sample size is at least 4,000 neonates who receive interventions. After anonymization, the data is pooled in a common database and descriptive and statistical analysis is performed globally and in subgroups. Possible correlations will be investigated with phi coefficient and chi square testing. Ethics and dissemination: Consent of the institutional review board of the Technical University Dresden was obtained for the local data collection under the number BO-EK-198042022. Additionally, approval of local ethical or institutional review boards will be obtained by the participating hospitals if required. Results will be published in peer-reviewed journals and presented at suitable scientific conferences.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.