https://nova.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 The enigma of the adrenarche: identifying the early life mechanisms and possible role in postnatal brain development https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45257 Wed 26 Oct 2022 15:32:17 AEDT ]]> Ganaxolone: a new treatment for neonatal seizures https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:31504 A agonist neurosteroid, as a novel neonatal therapy. We discuss evidence that ganaxolone can provide both seizure control and neuroprotection with a high safety profile when administered early following birth-related hypoxia, and show evidence that it is likely to prevent or reduce the incidence of the enduring disabilities associated with preterm birth, cerebral palsy, and epilepsy. We suggest that ganaxolone is an ideal anti-seizure treatment because it can be safely used prospectively, with minimal or no adverse effects on the neonatal brain.]]> Wed 15 Dec 2021 16:09:15 AEDT ]]> Evaluating changes in GABAergic and glutamatergic pathways in early life following prenatal stress and postnatal neurosteroid supplementation https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:52465 Wed 11 Oct 2023 20:36:57 AEDT ]]> Effects of prenatal stress on fetal neurodevelopment and responses to maternal neurosteroid treatment in guinea pigs https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:16551 Wed 11 Apr 2018 17:05:24 AEST ]]> Blocked, delayed, or obstructed: what causes poor white matter development in intrauterine growth restricted infants? https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:31317 Wed 10 Nov 2021 15:05:04 AEDT ]]> Ganaxolone versus Phenobarbital for Neonatal Seizure Management https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50851 Wed 09 Aug 2023 09:38:31 AEST ]]> Effects of prenatal stress on behavioural and neurodevelopmental outcomes are altered by maternal separation in the neonatal period https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:48670 Tue 28 Mar 2023 10:15:40 AEDT ]]> Maternal stress in pregnancy affects myelination and neurosteroid regulatory pathways in the guinea pig cerebellum https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:33789 Tue 15 Jan 2019 12:58:06 AEDT ]]> Birth and neonatal transition in the guinea pig: experimental approaches to prevent preterm birth and protect the premature fetus https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:35228 in utero. This allows adverse intrauterine conditions to make a sustained impact on the developing brain like in compromised human pregnancies. In addition, the brain is exposed to a protective neurosteroid environment in utero, which has been suggested to promote development in the guinea pig and the human. Moreover, in utero stresses that have been shown to adversely affect long term neurobehavioral outcomes in clinical studies, can be modeled successfully in guinea pigs. Overall, these parallels to the human have led to increasing interest in the guinea pig for translational studies of treatments and therapies that potentially improve outcomes following adverse events in pregnancy and after preterm birth.]]> Tue 02 Jul 2019 11:37:43 AEST ]]> Loss of neurosteroid-mediated protection following stress during fetal life https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:24307 A receptor subunits that normally heighten neurosteroid sensitivity. These stressors also result in altered placental allopregnanolone metabolism pathways. These findings suggest that reduced neurosteroid production and action in the perinatal period may contribute to some of the adverse neurodevelopmental and behavioural outcomes that result from these pregnancy compromises. Studies examining perinatal steroid supplementation therapy with non-metabolisable neurosteroid analogues to improve these outcomes are warranted.]]> Thu 21 Oct 2021 12:51:39 AEDT ]]> Injury of the developing cerebellum: a brief review of the effects of endotoxin and asphyxial challenges in the late gestation sheep fetus https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:16534 Thu 21 Jul 2022 15:38:24 AEST ]]> Cerebellar changes in guinea pig offspring following suppression of neurosteroid synthesis during late gestation https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:32953 A receptor subunit composition, which may further limit neurosteroid action. The objective of this study was to determine the effects of suppression of allopregnanolone levels on the markers of development and functional outcome. Pregnant guinea pigs were treated with finasteride at a dose (25 mg/kg maternal weight) shown to suppress allopregnanolone between 60 days of gestation until delivery (term ~71 days). The cerebella from neonates, whose mothers were treated with finasteride or vehicle during pregnancy, were collected at postnatal age 8. Pups that received finasteride displayed significantly greater glial fibrillary acid protein area coverage and reduced GABAA receptor a α₆-subunit messenger RNA within the cerebellum than pups that were exposed to vehicle. These findings indicate that loss of neurosteroid action on the foetal brain in late gestation produces prolonged astrocyte activation and reductions in GABAA receptor a α₆-subunit expression. These changes may contribute to the long-term changes in function associated with preterm birth.]]> Thu 16 Aug 2018 13:35:57 AEST ]]> Increased anxiety-like phenotype in female guinea pigs following reduced neurosteroid exposure in utero https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:32952 Thu 16 Aug 2018 13:35:51 AEST ]]> Stress in pregnancy: a role for neuroactive steroids in protecting the fetal and neonatal brain https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8296 Sat 24 Mar 2018 08:40:34 AEDT ]]> Stress in pregnancy activates neurosteroid production in the fetal brain https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:986 A receptor and suppress the fetal CNS activity. These steroids are synthesized in the fetal brain either from cholesterol or from circulating precursors derived from the placenta. The concentrations of allopregnanolone are remarkably high in the fetal brain and rise further in response to acute hypoxic stress, induced by constriction of the umbilical cord. This response may result from the increased 5α-reductase and cytochrome P-450SCC expression in the brain. These observations suggest that the rise in neurosteroid concentrations in response to acute hypoxia may represent an endogenous protective mechanism that reduces excitotoxicity following hypoxic stress in the developing brain. In contrast to acute stress, chronic hypoxemia induces neurosteroidogenic enzyme expression without an increase in neurosteroid concentrations and, therefore, may pose a greater risk to the fetus. At birth, the allopregnanolone concentrations in the brain fall markedly, probably due to the loss of placental precursors; however, stressors, including hypoxia and endotoxin-induced inflammation, raise allopregnanolone concentrations in the newborn brain. This may protect the newborn brain from hypoxia-induced damage. However, the rise in allopregnanolone concentrations was also associated with increased sleep. This rise in sedative steroid levels may depress arousal and contribute to the risk of sudden infant death syndrome. Our recent findings indicate that acute hypoxic stress in pregnancy initiates a neurosteroid response that may protect the fetal brain from hypoxia-induced cell death, whereas the decline in allopregnanolone levels after birth may result in greater vulnerability to brain injury in neonates.]]> Sat 24 Mar 2018 08:29:48 AEDT ]]> Neuroactive steroids induce changes in fetal sheep behavior during normoxic and asphyxic states https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:14494 Sat 24 Mar 2018 08:21:40 AEDT ]]> Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on foetal guinea pig brain development https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:16511 Sat 24 Mar 2018 08:04:17 AEDT ]]> Neuroactive steroids in pregnancy: key regulatory and protective roles in the foetal brain https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:16519 Sat 24 Mar 2018 08:01:21 AEDT ]]> Effect of maternal administration of allopregnanolone before birth asphyxia on neonatal hippocampal function in the spiny mouse https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:16516 A receptor, and that has anti-apoptotic and anti-excitotoxic actions, reducing brain damage in adult animal models of brain injury. We sought to determine if prophylactic treatment of the pregnant female with a single dose of this steroid could reduce birth asphyxia-induced losses in hippocampal function at 5 days of age (P5) in spiny mouse neonates (Acomys cahirinus). At 37 days gestation (term = 39 days) and 1 h before inducing birth asphyxia, spiny mice dams were injected subcutaneously (0.2 ml) with either 3 mg/kg allopregnanolone or 20% w/v β-cyclodextrin vehicle. One hour later, fetuses were either delivered immediately by caesarean section (control group) or exposed to 7.5 min of in utero asphyxia, causing acidosis and hypoxia. At P5, ex vivo hippocampal plasticity was assessed, or brains collected to determine cell proliferation (proliferating cell nuclear antigen; PCNA) or calcium channel expression (inositol trisphosphate receptor type 1; IP₃R1) using immunohistochemistry. Allopregnanolone partially prevented the decrease in long term potentiation at P5, and the asphyxia-induced increase in IP₃R1 expression in CA1 pyramidal neurons. There was no effect of allopregnanolone on the asphyxia induced impairment of the input/output (I/O) curve and paired-pulse facilitation (PPF). In control birth pups, maternal allopregnanolone treatment caused significant changes in short term post-synaptic plasticity and also reduced hippocampal proliferation at P5. These findings show that allopregnanolone can modulate hippocampal development and synaptic function in a normoxic or hypoxic environment, possibly by modifying calcium metabolism. Best practice for treatment dose and timing of treatment will need to be carefully considered.]]> Sat 24 Mar 2018 08:01:15 AEDT ]]> Brain allopregnanolone in the fetal and postnatal rat in response to uteroplacental insufficiency https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5459 Sat 24 Mar 2018 07:48:11 AEDT ]]> Models of perinatal compromises in the guinea pig: their use in showing the role of neurosteroids in pregnancy and the newborn https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:29502 Sat 24 Mar 2018 07:29:45 AEDT ]]> Neurosteroids in the fetus and neonate: potential protective role in compromised pregnancies https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4813 Sat 24 Mar 2018 07:20:45 AEDT ]]> Neurosteroid-based intervention using Ganaxolone and Emapunil for improving stress-induced myelination deficits and neurobehavioural disorders https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47891 Mon 06 Feb 2023 12:21:53 AEDT ]]> A tale of two steroids: the importance of the androgens DHEA and DHEAS for early neurodevelopment https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45493 Fri 28 Oct 2022 15:53:26 AEDT ]]> Antenatal prevention of cerebral palsy and childhood disability: is the impossible possible? https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:43394 Fri 16 Sep 2022 09:44:21 AEST ]]>