25504885

PMC4468050

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.

CDC Public Access

DP00187-5/DP/NCCDPHP CDC HHS/United States
P30 AG035982/AG/NIA NIH HHS/United States
P30 AG035982/AG/NIA NIH HHS/United States
P30 HD002528/HD/NICHD NIH HHS/United States
P30 HD002528/HD/NICHD NIH HHS/United States
R01 HL049041/HL/NHLBI NIH HHS/United States
R01 HL049041-13/HL/NHLBI NIH HHS/United States
R03 HD062734/HD/NICHD NIH HHS/United States
R03 HD062734/HD/NICHD NIH HHS/United States
S10 RR029577/RR/NCRR NIH HHS/United States
S10 RR29577/RR/NCRR NIH HHS/United States
UL1 RR033179/RR/NCRR NIH HHS/United States
UL1RR033179/RR/NCRR NIH HHS/United States