Chronic fetal hypoxia affects axonal maturation in guinea pigs during development: a longitudinal Diffusion Tensor Imaging and T2 mapping study

Details

• Alternative Title:
  J Magn Reson Imaging
• Personal Author:
  Kim, Jieun ; Choi, In-Young ; Dong, Yafeng ; Wang, Wen-Tung ; Brooks, William M. ; Weiner, Carl P. ; Lee, Phil
• Description:
  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.
  
  
• Subjects:
  Animals Anisotropy Anoxia Article Brain Brain Development Brain Injuries Chronic Disease Diffusion Tensor Imaging DTI Female Fetal Hypoxia Guinea Pig Guinea Pigs Image Processing, Computer-Assisted Longitudinal Studies Magnetic Resonance Imaging Male Neurons Prenatal Brain Injury Reverse Transcriptase Polymerase Chain Reaction T2

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• Source:
  J Magn Reson Imaging. 42(3):658-665.
• Pubmed ID:
  25504885
• Pubmed Central ID:
  PMC4468050
• Document Type:
  Journal Article
• Funding:
  DP00187-5/DP/NCCDPHP CDC HHS/United States ; P30 AG035982/AG/NIA 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 ; 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
• Volume:
  42
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:22768e8131ff30eebe6fc76a76522595aff2fd8f91e2d979ca2891fd1f920f6f
• Download URL:
  https://stacks.cdc.gov/view/cdc/35068/cdc_35068_DS1.pdf
• File Type:
  [PDF - 1.71 MB ]