PhD Scientific Days 2021

TT_I_P: Theoretical and Translational Medicine I. Posters

Animal models of preeclampsia for investigating cerebrovascular autoregulation – advantages and limitations

Text of the abstract

Introduction: Preeclampsia is a leading cause of both maternal and fetal morbidity and mortality, affecting ~8% of pregnancies. Despite of extensive research, the underlying mechanisms are still unclear. Many animal models have been developed, which share many of the features, but do not include the complete symptoms present in this human disease. One of the less addressed issue in preeclampsia is the effects of increased systemic blood pressure on the autoregulation of cerebral blood flow.
Aims: Thus, we aimed to elucidate whether the available animal models are suitable to study the adaptation of cerebral autoregulation in preeclampsia.
Methods: We have reviewed the literature (PUBMED) regarding the animal models of preeclampsia.
Results: In general, animal models of preeclampsia can be divided into 4 groups: 1) spontaneous, 2) surgically induced, 3) pharmacologically induced and 4) transgenic. Model 1: the Dahl salt-sensitive rat is a genetic model of kidney disease and hypertension. Model 2: the reduced uterine perfusion pressure (RUPP) rat elicited with a combination of aortic constriction and occlusion of the uterine-ovarian arteries. Model 3: inhibition of nitric oxide synthase in rats by L-NAME at different gestational stages, which leads to preeclampsia-like symptoms. Model 4: overexpression of the VEGF antagonist sFlt-1 via the administration of viral vectors results in pregnancy-specific proteinuria and hypertension in rats.
Conclusion: Preeclampsia is a disease unique to humans. Although several animal models exist and some of them have placental lesions, none of them is presenting the complexity of human disease, thus extrapolation of the findings to human preeclampsia must be made with caution. Importantly, the effects of high systemic blood pressure on the mechanosensitive mechanisms contributing to the adaptation of cerebral autoregulation providing protection against stroke – which can occur in preeclampsia - have not yet been addressed. Therefore, at first, comparison of cerebrovascular adaptation should be studied in young and old pregnant rats, which would help to elucidate the effects and underlying mechanisms of cerebrovascular adaptations in preeclampsia.
Funding: OTKA132596, K_19; EFOP-3.6.3-VEKOP-16-2017-00009, Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine