ArticleBrain and behavior2024
Zuranolone therapy protects frontal cortex neurodevelopment and improves behavioral outcomes after preterm birth.
Article in Brain and behavior, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Divergent representation and processing of task cues in sensory and prefrontal cortices of preterm-born mice.Nature communications · 2026Article
- Zuranolone therapy protects frontal cortex neurodevelopment and improves behavioral outcomes after preterm birth.Brain and behavior · 2024Article
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5 authors.
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Abstract
backgroundPreterm birth is associated with brain injury and long-term behavioral abnormalities, for which there are limited prevention options. When born preterm, infants prematurely lose placental neurosteroid (allopregnanolone) support. This increases the risk of excitotoxic damage to the brain, which increases the risk of injury, causing long-term deficits in behavior, myelination, and alterations to neurotransmitter pathways. We propose that postnatal restoration of neurosteroid action through zuranolone therapy will reduce neurological impairments following preterm birth.
methodsGuinea pig dams underwent survival cesarean section surgery to deliver pups prematurely (GA64) or at term (GA69). Between birth and term equivalence age, preterm pups received vehicle (15% β-cyclodextrin) or the allopregnanolone analogue zuranolone (1 mg/kg/day). Behavioral analysis was performed at postnatal day (PND) 7 and 40, before tissue collection at PND 42. Immunostaining for myelin basic protein (MBP), as well as real-time polymerase chain reaction to characterize oligodendrocyte lineage and neurotransmitter pathways, was performed in frontal cortex tissues.
resultsZuranolone treatment prevented the hyperactive phenotype in preterm-born offspring, most markedly in males. Additionally, preterm-related reductions in MBP were ameliorated. Several preterm-related alterations in mRNA expression of dopaminergic, glutamatergic, and GABAergic pathways were also restored back to that of a term control level.
conclusionThis is the first study to assess zuranolone treatment as a neuroprotective therapy following preterm birth. Zuranolone treatment improved behavioral outcomes and structural changes in the preterm offspring, which continued long term until at least a late childhood timepoint. Clinical studies are warranted for further exploring the neuroprotective possibilities of this treatment following preterm birth.
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