Chronic fetal hypoxia affects axonal maturation in guinea pigs during development: A longitudinal diffusion tensor imaging and T₂ mapping study

Abstract

Purpose Chronic hypoxemia is the prime cause of fetal brain injury and long-term sequelae such as neurodevelopmental compromise, seizures and cerebral palsy. This study aims to investigate the impact of chronic hypoxemia on neonatal brains, and follow developmental alterations and adaptations non-invasively in a guinea pig model. Materials and Methods Thirty guinea pigs underwent either normoxic and hypoxemic conditions during the critical stage of brain development (0.7 gestation) and studied prenatally (n=16) or perinatally (n=14). Fourteen newborns (7 hypoxia and 7 normoxia group) were scanned longitudinally to characterize physiological and morphological alterations, and axonal myelination and injury using in vivo DTI, T2 mapping, and T2-weighted MRI. Sixteen fetuses (8 hypoxia and 8 normoxia) were studied ex vivo to assess hypoxia-induced neuronal injury/loss using Nissl staining and quantitative reverse transcriptase Polymerase Chain Reaction methods. Results Developmental brains in the hypoxia group showed lower fractional anisotropy in the corpus callosum (−12%, p=0.02) and lower T2 values in the hippocampus (−16%, p=0.003) compared with the normoxia group with no differences in the cortex (p>0.07), indicating vulnerability of the hippocampus and cerebral white matter during early development. Fetal guinea pig brains with chronic hypoxia demonstrated an over-tenfold increase in expression levels of hypoxia index genes such as erythropoietin and HIF-1α, and an over 40% reduction in neuronal density, confirming prenatal brain damage. Conclusion In vivo MRI measurement, such as DTI and T2 mapping, provides quantitative parameters to characterize neuro-developmental abnormalities and to monitor the impact of prenatal insult on the postnatal brain maturation of guinea pigs.

Youth friendly sexual and reproductive health service utilization among high and preparatory school students in Debre Tabor town, Northwest Ethiopia: A cross sectional study

“…This study also indicated that youth who had discussions about RH services with health workers, family, teachers, peers, and sexual partners were more likely to utilize the services than their counterparts. The finding of this study is consistent with the findings in Gondar [28] and in Madawalabo [29]. This might be due to prior information on RH service increase their utilization, which would in turn motivate them to use the service.…”

“…Students who had sexual intercourse within the past one year were more likely to utilize RH service than abstainers. This finding is similar with the studies carried out in Gondar [28] and in West Badewacho woreda, Ethiopia [18]. This might be due to the fact that many of reproductive health service components (contraception) might be used when youths have perceived reproductive health risks related to sexual intercourse.…”

Disease-Causing SDHAF1 Mutations Impair Transfer of Fe-S Clusters to SDHB

“…We found that impaired CII activity in SDHAF1-deficient patient-derived cells led to elevated intracellular succinate levels, which may have caused the elevation of HIF levels by competitively inhibiting prolyl hydroxylases. Another consequence of succinate accumulation may involve the covalent succinylation of lysine residues in numerous target proteins, including SDHA, isocitrate dehydrogenase (IDH) and pyruvate dehydrogenase (PDH), leading to important metabolic changes that potentially contribute to patients’ phenotype (Higashida et al, 2011; Jalal et al, 2015; Kim et al, 2015). No satisfactory treatment is currently available for most mitochondrial disorders and the therapeutic interventions have been focused on supplementation with antioxidants and vitamins that can reduce reactive oxygen species (Mahoney et al, 2002).…”

Cerebrovascular adaptations to chronic hypoxia in the growth restricted lamb

“…In our sheep model of IUGR we have reported hypomyelination and axonal injury after birth (Miller et al, 2014), but we do not yet know whether this represents a transient response or a permanent injury. Fetal hypoxemia occurs in response to chronic placental insufficiency, which is likely to lead to a reduction in oxygen delivery to the brain (Rees et al, 2011), and in turn lead to fetal brain injury and long-term sequelae such as neurodevelopmental compromise, seizures, and cerebral palsy (Kim et al, 2014). Oligodendrocyte maturation and myelination are at their peak in the fetal brain in mid-to late-gestation during this period of placental insufficiency and chronic hypoxia (Back et al, 2007).…”