Previous adaptation triggers distinct molecular pathways and modulates early and long-term neuroprotective effects of pregnancy swimming preventing neonatal hypoxia-ischemia damage in rats

Abstract Neonatal hypoxia-ischemia (HI) is one of the main causes of neurological damage in newborns. Pregnancy swimming (PS) alters brain maturation and has neuroprotective effects following HI; however, variables such as timing play a decisive role in its effects. Prior to mating, we tested if adaptation of female rats to a tank filled with water at 32°C for 7 days before mating, modulates PS benefits. After mating, rats swam 20min/day or remained in standard cages. Seven-day-old pups were subjected to HI (right common carotid artery occlusion followed by FiO2 8% for 60 min). Animals were divided into 8 experimental groups, adaptation, swimming and injury. Astrocytic reactivity, apoptosis-related proteins, neurotrophins and cell survival markers expression were assessed in the hippocampus 24h after HI. From PND45, animals performed behavioral tests followed by histological assessment. Three-way ANOVA showed a significant increase in astrogliosis only in non-adapted HI animals. Swimming decreased apoptotic cell death despite adaptation period in both exercised groups. Cylinder evidenced HI impairments; no effect of swimming or adaptation period were observed. In the open field, only HI animals whose mothers had been adapted had increased locomotion; moreover, swimming reversed HI damage. Hemisphere and hippocampus were preserved only in the HI group whose mothers swam before mating, suggesting a preconditioning effect mediated by the adaptation. In summary, adaptation period plays a major role in the mechanisms involving neuroprotection afforded by PS and needs to be further explored in future studies involving damage to the neonatal brain.