https://nova.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 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 ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50851 Wed 09 Aug 2023 09:38:31 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:16534 Thu 21 Jul 2022 15:38:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8296 Sat 24 Mar 2018 08:40:34 AEDT ]]> 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-450_SCC 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 ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:14494 Sat 24 Mar 2018 08:21:40 AEDT ]]> 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 ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4813 Sat 24 Mar 2018 07:20:45 AEDT ]]>