Efeitos da hipóxia isquêmica pré-natal e da separação materna no risco cardiovascular e no comportamento de ratos

Abstract

Stressful events in the perinatal period can be determinant for the genesis of pathologies, considering that the presence of stressors in the perinatal period has been associated with increased susceptibility to psychiatric disorders, such as anxiety and depression, and cardiovascular diseases. In the present study, rats were submitted to prenatal hypoxia- ischemic (HI) and maternal separation (SM) to mimic prenatal and postnatal stressors, respectively. Therefore, the aim of the present study is to evaluate the effects of HI and MS, alone and in combination, on cardiovascular risk and on anxiety-like and depressive-like behaviors. On the 18th day of gestation, pregnant Wistar females were randomly divided into control (NC), surgical control (SHAM) and hypoxia-ischemic (HI) groups. The HI rats had their uterine horns exposed and their uterine arteries were clamped for 45 minutes. In the SHAM group, the females were submitted to the same procedure, except for the clamping of the uterine arteries. After the full-term birth of the pups, the litters of the three groups were subdivided into non-separated and maternal separation. The MS protocol took place from the first to the fifteenth postnatal day for 180 minutes. At P30 and P90, the animals of the six groups were submitted to the plus maze and open field test, to assess anxiety-like behavior, and to the sucrose preference test and forced swimming to investigate depressive-like behavior. Hemodynamic, vascular parameters and oxidative stress analysis were performed to assess the cardiovascular profile. HI and MS per se seem to consistently generate cardiovascular changes, such as endothelial dysfunction, decreased GPx activity and nitrite production, in addition to increased systemic blood pressure. In addition, early stress led the animals to develop depressive-like behavior. The combination of the two stresses maintains the depressive-like behavior, however, it does not appear to lead to cardiovascular dysfunction. The dataset suggests that early stress produces permanent changes in animals that are consistent with increased cardiovascular risk and susceptibility to psychiatric disorders