Intrauterine adverse conditions may be responsible for long-lasting damages which impact health even during adult phase. Hypoxic-ischemic (HI) events are a relevant cause of newborn mortality and the principal factor leading to permanent brain lesions. Using a model in which the ovarian and uterine flux of a pregnant rat is obstructed for 45 min we have described oligodendrocyte death, astrogliosis and neuronal loss. In this work we investigated hippocampal neuronal population and performed a functional evaluation of memory and learning of young rats that had been affected by prenatal HI. Anesthetized Wistar rats on the 18th gestation day had the uterine horns exposed and the ovarian and uterine arteries clamped for 45 min (HI group). Sham-operated rats (SH group) had the horns exposed but no arteries were clamped. We measured the levels of different proteins related to excitatory/inhibitory transmission in the hippocampi of young pups (P45). Histological evaluation was also performed in order to characterize hippocampal neuronal population. Rats from both groups were tested through Novel Object Recognition Test (NORT) using two inter-trial intervals: 5 min and 8 h. Here we show a loss in the total number of hippocampal neurons although the immunostaining of parvalbumin and levels of GAD enzyme were increased in HI group. Functional assessment indicated a marked difference concerning HI learning and memory abilities. Our results reflect permanent damages concerning GABA function which may disturb neurotransmitter homeostasis leading to the observed deficits in learning and memory.
Hypoxic-ischemic (HI) injury is an important cause of death and disabilities. Despite all improvements in neonatal care, the number of children who suffer some kind of injury during birth has remained stable in the last decade. A great number of studies have shown alterations in neural cells and many animal models have been proposed in the last 5 decades. Robinson et al. (2005) proposed an HI model in which the uterine arteries are temporarily clamped on the 18th gestation day. The findings were quite similar to the ones observed in postmortem studies. The white matter is clearly damaged, and a great amount of astrogliosis takes place both in the gray and white matters. Motor changes were also found but no data regarding the cerebellum, an important structure related to motor performance, was presented. Using this model, we have shown an increased level of iNOS at P0 and microgliosis and astrogliosis at P9, and astrogliosis at P23 (up to 4 weeks from the insult). NO is important in migration, maturation, and synaptic plasticity, but in exacerbated levels it may also contribute to cellular and tissue damage. We have also evaluated oligodendroglia development in the cerebellum. At P9 in HI animals, we found a decrease in the number of PDGFRα+ cells and an apparent delay in myelination, suggesting a failure in oligodendroglial progenitors migration/maturation and/or in the myelination process. These results point to an injury in cerebellar development that might help to explain the motor problems in HI.
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