Abstract
1IntroductionIntrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR.2MethodsUtero‐placental insufficiency was induced by meso‐ovarian vessel cauterization (CMO) in pregnant rats at embryonic day 17 (E17). Learning performance in an aquatic learning test was evaluated 25 days after birth and during 10 days. Some synaptic proteins were analyzed (PSD95, Synaptophysin) by Western blot and immunohistochemistry.3ResultsPlacental insufficiency in CMO pups was associated with spatial memory deficits, which are correlated with a CI above the normal range. CMO pups presented altered levels of synaptic proteins PSD95 and synaptophysin in the hippocampus.4ConclusionsThe results of this study suggest that learning disabilities may be associated with altered development of excitatory neurotransmission and synaptic plasticity. Although interspecific differences in fetal response to placental insufficiency should be taken into account, the translation of these data to humans suggest that both IUGR babies and babies with a normal birth weight but with intrauterine Doppler alterations and abnormal CI should be closely followed to detect neurodevelopmental alterations during the postnatal period.
Highlights
Intrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood
Children born with IUGR are predisposed to long-term cognitive and neurodevelopmental impairment that is associated with learning difficulties and decreased academic performance (Arcangeli, Thilaganathan, Hooper, Khan, & Bhide, 2012; de Bie, Oostrom, & Delemarre-van de Waal, 2010)
Of the experimental group, cephalization index (CI) values above 1.32 were associated with an increased risk of poor spatial memory performance (EL below the 25th percentile, estimated in the control group), ranging from 33% in controls (1 of 3) to 58% in pups from CMO-operated mothers (15 of 26) (Figure 2c). These results suggest that a high CI associated with utero- placental insufficiency predisposed the pups studied to learning and memory deficits
Summary
Intrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR. A high CI in IUGR babies seems to be indicative of intrauterine blood flow redistribution, known as the brain sparing effect, and is strongly correlated with a reduction in IQ, difficulties in creative problem solving, deficits in attention and executive functions, and alterations in visuomotor organization (Flood et al, 2014; Van den Broek, Kok, Houtzager, & Scherjon, 2010)
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