Sex-Dependent Effects of Prenatal Stress on Seizure Susceptibility and Neurodegeneration in Neonatal Rats

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Background: Prenatal stress affects fetal neurodevelopment and may increase the risk of seizures. This study aimed to analyze the impact of maternal restraint stress during pregnancy on neonatal status epilepticus (SE) in rats. Methods: Pregnant Wistar rats were subjected to restraint stress from gestation days 12 to 20. Offspring were assessed for body weight, size, and corticosterone levels. SE was induced in postnatal day 7 rats using the lithium–pilocarpine model. Neurodegeneration was analyzed using Fluoro-Jade C staining. Results: Maternal restraint stress resulted in reduced weight gain for the mothers and lower body weight and size for their offspring. Stressed neonates exhibited higher levels of serum corticosterone. Male neonates exhibited shorter latency to stage 1 seizures and increased hippocampal neurodegeneration compared with control males, whereas female neonates were largely unaffected. Conclusions: Maternal restraint stress produced only mild, sex-dependent effects on neonatal seizure susceptibility, affecting males but not females, suggesting a limited yet selective influence of prenatal stress on early brain vulnerability.