Neuroplasticity Mechanisms and Synaptic Remodelling in Response to Environmental Enrichment Following Neonatal Hypoxia-Ischaemia in a Rat Model: Translational Implications for Nigerian Neonatal Care

Background: Neonatal hypoxia-ischaemia is a leading cause of neurodevelopmental disability in Nigeria, where intrapartum asphyxia rates remain high due to delayed obstetric care and suboptimal resuscitation infrastructure. Environmental enrichment paradigms have demonstrated neuroplasticity-promoting properties in animal models, but the synaptic remodelling mechanisms and critical windows of efficacy have not been characterised in relation to conditions mimicking Nigerian neonatal care deficits. Objectives: This study aims to characterise the effects of postnatal environmental enrichment on brain-derived neurotrophic factor expression, dendritic spine density, synaptophysin immunoreactivity, and long-term potentiation induction in hippocampal slices of neonatal Wistar rats subjected to standardised hypoxia-ischaemia injury, and to identify critical developmental windows for maximal neuroplastic benefit. Methods: Ninety rat pups will undergo right carotid artery ligation followed by 8% oxygen exposure at postnatal day 7. Three enrichment initiation timepoints (postnatal days 10, 17, and 24) will be compared with hypoxia-ischaemia controls and sham-operated animals. Behavioural testing, hippocampal electrophysiology, immunohistochemistry, and western blot will be performed at postnatal day 35. Two-way ANOVA will assess injury-enrichment interaction effects. Expected Outcomes: Early environmental enrichment is hypothesised to produce the greatest brain-derived neurotrophic factor induction, highest dendritic spine density, and superior long-term potentiation amplitude, with efficacy declining with later initiation. Conclusion: Findings will provide mechanistic justification for early neurostimulation protocols in Nigerian neonatal intensive care units. Keywords: neonatal hypoxia-ischaemia, neuroplasticity, environmental enrichment, brain-derived neurotrophic factor, synaptic remodelling.