Fetal growth restriction(FGR)describes a fetus that has not grown to its expected biological potential in utero.FGR can result from maternal,fetal,or placental complications,though it is commonly caused by placental i...Fetal growth restriction(FGR)describes a fetus that has not grown to its expected biological potential in utero.FGR can result from maternal,fetal,or placental complications,though it is commonly caused by placental insufficiency.The prolonged hypoxic environment the FGR fetus is exposed to has detrimental effects on the newborn,which extends to adverse long-term neurological outcomes in a significant proportion of FGR infants(Malhotra et al.,2019).Unfortunately,there are currently no therapies to reduce the adverse neurological outcomes in FGR.Neuronal injury is evident in the FGR brain,and therefore understanding which neurons are lost and how they are lost will aid in the selection of treatment options for FGR.展开更多
Fetal growth restriction(FGR)is one of the most common contributors to increased risk of mortality in the fetal/neonatal period and long-term morbidity in the infant(Malhotra et al.,2019).FGR can arise from many patho...Fetal growth restriction(FGR)is one of the most common contributors to increased risk of mortality in the fetal/neonatal period and long-term morbidity in the infant(Malhotra et al.,2019).FGR can arise from many pathophysiological processes associated with maternal,fetal,genetic,or placental compromise;however,placental insufficiency is the most common cause of FGR.Placental insufficiency during pregnancy results in chronic fetal hypoxia where a lack of oxygen and nutrients supply to the developing fetus impacts normal development of the fetus.展开更多
Neonatal hypoxia-ischemia(HI) results in losses of serotonergic neurons in specific dorsal raphé nuclei. However, not all serotonergic raphé neurons are lost and it is therefore important to assess the funct...Neonatal hypoxia-ischemia(HI) results in losses of serotonergic neurons in specific dorsal raphé nuclei. However, not all serotonergic raphé neurons are lost and it is therefore important to assess the function of remaining neurons in order to understand their potential to contribute to neurological disorders in the HI-affected neonate. The main objective of this study was to determine how serotonergic neurons, remaining in the dorsal raphé nuclei after neonatal HI, respond to an external stimulus(restraint stress). On postnatal day 3(P3), male rat pups were randomly allocated to one of the following groups:(i) control + no restraint(n = 5),(ii) control + restraint(n = 6),(iii) P3 HI + no restraint(n = 5) or(iv) P3 HI + restraint(n = 7). In the two HI groups, rat pups underwent surgery to ligate the common carotid artery and were then exposed to 6% O2 for 30 minutes. Six weeks after P3 HI, on P45, rats were subjected to restraint stress for 30 minutes. Using dual immunolabeling for Fos protein, a marker for neuronal activity, and serotonin(5-hydroxytrypamine; 5-HT), numbers of Fos-positive 5-HT neurons were determined in five dorsal raphé nuclei. We found that restraint stress alone increased numbers of Fos-positive 5-HT neurons in all five dorsal raphé nuclei compared to control animals. However, following P3 HI, the number of stress-induced Fos-positive 5-HT neurons was decreased significantly in the dorsal raphé ventrolateral, interfascicular and ventral nuclei compared with control animals exposed to restraint stress. In contrast, numbers of stress-induced Fos-positive 5-HT neurons in the dorsal raphé dorsal and caudal nuclei were not affected by P3 HI. These data indicate that not only are dorsal raphé serotonergic neurons lost after neonatal HI, but also remaining dorsal raphé serotonergic neurons have reduced differential functional viability in response to an external stimulus. Procedures were approved by the University of Queensland Animal Ethics Committee(UQCCR958/08/NHMRC) on February 27, 2009.展开更多
Intrauterine growth restriction(IUGR)occurs when a baby is unable to grow normally due to receiving inadequate nutrients while developing in the womb.IUGR is a leading cause of perinatal death and longterm disability....Intrauterine growth restriction(IUGR)occurs when a baby is unable to grow normally due to receiving inadequate nutrients while developing in the womb.IUGR is a leading cause of perinatal death and longterm disability.The fetal brain is particularly vulnerable to IUGR conditions and adverse outcomes range from learning,attention and behavioral difficulties,to cerebral palsy.Due to medical advancements,more IUGR babies now survive,resulting in an even greater burden of disability.展开更多
基金supported by The University of Queensland Stimulus Fellowship(to JAW)Queensland Children’s Hospital Foundation Grant(No.WIS0012021,to support KB)。
文摘Fetal growth restriction(FGR)describes a fetus that has not grown to its expected biological potential in utero.FGR can result from maternal,fetal,or placental complications,though it is commonly caused by placental insufficiency.The prolonged hypoxic environment the FGR fetus is exposed to has detrimental effects on the newborn,which extends to adverse long-term neurological outcomes in a significant proportion of FGR infants(Malhotra et al.,2019).Unfortunately,there are currently no therapies to reduce the adverse neurological outcomes in FGR.Neuronal injury is evident in the FGR brain,and therefore understanding which neurons are lost and how they are lost will aid in the selection of treatment options for FGR.
基金supported by a University of Queensland Stimulus Fello wship。
文摘Fetal growth restriction(FGR)is one of the most common contributors to increased risk of mortality in the fetal/neonatal period and long-term morbidity in the infant(Malhotra et al.,2019).FGR can arise from many pathophysiological processes associated with maternal,fetal,genetic,or placental compromise;however,placental insufficiency is the most common cause of FGR.Placental insufficiency during pregnancy results in chronic fetal hypoxia where a lack of oxygen and nutrients supply to the developing fetus impacts normal development of the fetus.
基金funded by the National Health and Medical Research Council of Australia(to KMB)HER was supported by a University of Queensland International Research Tuition Award and University of Queensland Research Scholarship.JAW was supported by an Australian Postgraduate Award
文摘Neonatal hypoxia-ischemia(HI) results in losses of serotonergic neurons in specific dorsal raphé nuclei. However, not all serotonergic raphé neurons are lost and it is therefore important to assess the function of remaining neurons in order to understand their potential to contribute to neurological disorders in the HI-affected neonate. The main objective of this study was to determine how serotonergic neurons, remaining in the dorsal raphé nuclei after neonatal HI, respond to an external stimulus(restraint stress). On postnatal day 3(P3), male rat pups were randomly allocated to one of the following groups:(i) control + no restraint(n = 5),(ii) control + restraint(n = 6),(iii) P3 HI + no restraint(n = 5) or(iv) P3 HI + restraint(n = 7). In the two HI groups, rat pups underwent surgery to ligate the common carotid artery and were then exposed to 6% O2 for 30 minutes. Six weeks after P3 HI, on P45, rats were subjected to restraint stress for 30 minutes. Using dual immunolabeling for Fos protein, a marker for neuronal activity, and serotonin(5-hydroxytrypamine; 5-HT), numbers of Fos-positive 5-HT neurons were determined in five dorsal raphé nuclei. We found that restraint stress alone increased numbers of Fos-positive 5-HT neurons in all five dorsal raphé nuclei compared to control animals. However, following P3 HI, the number of stress-induced Fos-positive 5-HT neurons was decreased significantly in the dorsal raphé ventrolateral, interfascicular and ventral nuclei compared with control animals exposed to restraint stress. In contrast, numbers of stress-induced Fos-positive 5-HT neurons in the dorsal raphé dorsal and caudal nuclei were not affected by P3 HI. These data indicate that not only are dorsal raphé serotonergic neurons lost after neonatal HI, but also remaining dorsal raphé serotonergic neurons have reduced differential functional viability in response to an external stimulus. Procedures were approved by the University of Queensland Animal Ethics Committee(UQCCR958/08/NHMRC) on February 27, 2009.
基金This work was supported by National Health and Medical Research Council,Financial Markets Foundation for Children,Children’s Hospital Foundation,and Royal Brisbane and Women’s Hospital.
文摘Intrauterine growth restriction(IUGR)occurs when a baby is unable to grow normally due to receiving inadequate nutrients while developing in the womb.IUGR is a leading cause of perinatal death and longterm disability.The fetal brain is particularly vulnerable to IUGR conditions and adverse outcomes range from learning,attention and behavioral difficulties,to cerebral palsy.Due to medical advancements,more IUGR babies now survive,resulting in an even greater burden of disability.
