Publications by authors named "H K Palliser"
Preterm birth exposes the neonate to hypoxic-ischaemic and excitotoxic insults that impair neurodevelopment and are magnified by the premature loss of placentally supplied, inhibitory neurosteroids. The cerebellum is a neuronally dense brain region, which undergoes critical periods of development during late gestation, when preterm births frequently occur. We propose that neurosteroid replacement therapy using tiagabine and zuranolone will protect the cerebellum against preterm-associated insults.
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- High levels of the neurosteroid allopregnanolone during pregnancy are crucial for fetal brain development, but maternal stress can lower these levels, leading to myelination issues and increased behavioral disorders in childhood.
- Supplementing neurosteroid action with allopregnanolone analogues or using mitochondrial translocator protein (TSPO) ligands can help reverse developmental deficits that arise from low allopregnanolone levels.
- Preterm birth significantly decreases neurosteroid support, causing severe myelination deficits; however, postnatal treatments like ganaxolone can enhance myelination and reduce hyperactivity, suggesting potential therapeutic benefits of allopregnanolone after pregnancy issues.
The postnatal environment is challenging for the preterm neonate with exposure to hypoxic and excitotoxic events, amplified by premature loss of placentally derived neurosteroids. Between preterm birth and term equivalent age (TEA), cerebellar development continues despite these challenges. We hypothesize that neurosteroid replacement therapy during this time will support optimal cerebellar development.
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- Preterm birth can lead to brain injuries and long-term behavioral issues due to the loss of neurosteroid support from the placenta, increasing the risk of excitotoxic damage.
- The study used guinea pigs to test zuranolone, an analogue of allopregnanolone, by administering it to preterm pups and analyzing behavior and brain structure.
- Zuranolone treatment improved behavioral outcomes, prevented hyperactivity in male pups, and restored myelination and neurotransmitter pathways in preterm offspring, suggesting its potential as a neuroprotective therapy for preventing long-term impairments after preterm birth.
Article Synopsis
- - Preterm birth can lead to serious brain injuries and developmental disorders in newborns, and current treatments are ineffective in preventing these issues.
- - The study explores neurosteroid replacement therapy as a potential new treatment by using guinea pig brain cell cultures to understand how it might mitigate neurological damage related to preterm birth.
- - Results show that neurosteroids such as etifoxine and zuranolone can significantly reduce cell damage and improve marker expression following oxygen-glucose deprivation, indicating their neuroprotective effects might be due to reducing glutamate levels and enhancing brain-derived neurotrophic factor (BDNF).