ArticlePediatric research2019
Neurosteroid replacement therapy using the allopregnanolone-analogue ganaxolone following preterm birth in male guinea pigs.
Article in Pediatric research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Neuroactive steroids in the programming of neurodevelopment: implications of maternal obesity.Frontiers in endocrinology · 2025Review
- Functional Food Nutrients, Redox Resilience Signaling and Neurosteroids for Brain Health.International journal of molecular sciences · 2024Review
- Zuranolone therapy protects frontal cortex neurodevelopment and improves behavioral outcomes after preterm birth.Brain and behavior · 2024Article
- Perinatal compromise affects development, form, and function of the hippocampus part two; preclinical studies.Pediatric research · 2024Review
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target.Science advances · 2024Article
- Steroid Metabolome Analysis in Dichorionic Diamniotic Twin Pregnancy.International journal of molecular sciences · 2024Article
- β-carbolines that enhance GABAFrontiers in cellular neuroscience · 2024Article
- Transcriptional and bioinformatic analysis of GABAFrontiers in molecular neuroscience · 2023Article
- Neurosteroids and early-life programming: An updated perspective.Current opinion in endocrine and metabolic research · 2022Article
- Allopregnanolone: An overview on its synthesis and effects.Journal of neuroendocrinology · 2022Review
- Editorial: Preterm brain injury: Understanding injurious processes and new strategies for promoting neuroprotection and neuro-repair.Frontiers in physiology · 2022Article
- Examining Neurosteroid-Analogue Therapy in the Preterm Neonate For Promoting Hippocampal Neurodevelopment.Frontiers in physiology · 2022Article
- Fetal Zone Steroids and Estrogen Show Sex Specific Effects on Oligodendrocyte Precursor Cells in Response to Oxidative Damage.International journal of molecular sciences · 2021Article
- Impaired Oligodendrocyte Development Following Preterm Birth: Promoting GABAergic Action to Improve Outcomes.Frontiers in pediatrics · 2021Review
- Dysregulation of Neuronal Nicotinic Acetylcholine Receptor-Cholesterol Crosstalk in Autism Spectrum Disorder.Frontiers in molecular neuroscience · 2021Article
- Expression and Function of GABA Receptors in Myelinating Cells.Frontiers in cellular neuroscience · 2020Article
- Reduced Neurosteroid Exposure Following Preterm Birth and Its' Contribution to Neurological Impairment: A Novel Avenue for Preventative Therapies.Frontiers in physiology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChildren born preterm, especially boys, are at increased risk of developing attention deficit hyperactivity disorder (ADHD) and learning difficulties. We propose that neurosteroid-replacement therapy with ganaxolone (GNX) following preterm birth may mitigate preterm-associated neurodevelopmental impairment.
methodsTime-mated sows were delivered preterm (d62) or at term (d69). Male preterm pups were randomized to ganaxolone (Prem-GNX; 2.5 mg/kg subcutaneously twice daily until term equivalence), or preterm control (Prem-CON). Surviving male juvenile pups underwent behavioural testing at d25-corrected postnatal age (CPNA). Brain tissue was collected at CPNA28 and mature myelinating oligodendrocytes of the hippocampus and subcortical white matter were quantified by immunostaining of myelin basic protein (MBP).
resultsGanaxolone treatment returned the hyperactive behavioural phenotype of preterm-born juvenile males to a term-born phenotype. Deficits in MBP immunostaining of the preterm hippocampus and subcortical white matter were also ameliorated in animals receiving ganaxolone. However, during the treatment period weight gain was poor, and pups were sedated, ultimately increasing the neonatal mortality rate.
conclusionGanaxolone improved neurobehavioural outcomes in males suggesting that neonatal treatment may be an option for reducing preterm-associated neurodevelopmental impairment. However, dosing studies are required to reduce the burden of unwanted side effects.
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