///2017 Abstract Details
2017 Abstract Details2019-08-02T15:54:53-06:00

Demonstration of fetal brain sparing to both acute and chronic fetal asphyxia in mice: differential hypoxic inducible factor 1α expression and blood oxygen level dependent (BOLD) functional MRI.

Abstract Number: BP-01
Abstract Type: Original Research

Zohar Bromberg PhD1 ; Yehuda Gonosar PhD2; Natalie Corchai-Nachmansson PhD3; Rinat Abramovitch PhD4

Introduction: Blood oxygen level dependent (BOLD) MRI has been used to follow acute changes in organ perfusion in pregnant mice. We demonstrated that normoxic hypercapnia and i.v. phenylephrine caused acute reduction in BOLD MRI signal intensity (SI) in the placenta, fetal liver and fetal heart with minimal change in fetal brain. These changes were accompanied by increased pulsatility index and absent-diastolic flow on Doppler ultrasound in the umbilical artery, and fetal bradycardia. All these changes were consistent with acute placental hypoperfusion with fetal asphyxia and fetal brain sparing. Here we expose pregnant mice to chronic hypoxia (12% FiO2 from E10.5-E17.5) to assess whether there were either MRI or molecular changes suggestive of fetal brain sparing in chronic asphyxia.

Methods: Pregnant female ICR mice (n=18) were either normoxic or were exposed to chronic hypoxia (12% FiO2) on gestational days E10.5-17.5. On E17.5, mice were anesthetized with pentobarbital and scanned in a 4.7-T Bruker Biospec spectrometer. Mice breathed in consecutive 4 min periods a) air, b) 5% CO2 :21%O2, and c) 5% CO2 :95%O2. Placenta and fetal organs (liver, heart and brain) were identified on True-FISP images, and change in SI was analyzed from T2*-weighted GE images (TR/TE=147/10 ms); percentage change in SI induced by hypercapnia (ΔSCO2) was calculated and presented by color maps and time curves. Images were repeated at 30 second intervals for dynamic studies in response to brief acute episodes of hypercapnia (5% CO2). After MRI, fetuses and placentas were evaluated histologically. HIF-1α was assessed by immunofluorescence (Novus); neuro-apoptosis was assessed by TUNEL assay stain.

Results: Brief hypercapnic challenge in normal pregnancy caused immediate reduction in SI of placenta, fetal liver and fetal heart but not fetal brain, suggesting preferential fetal brain sparing. BOLD-fMRI responses to hypercapnia were diminished in chronic fetal hypoxia. HIF-1α expression was demonstrated in fetal liver but not in fetal brain in hypoxic animals, suggestive of chronic fetal brain sparing. There was neuro-apoptosis in the fetal brain tissue in chronic hypoxic animals.

Discussion: We observed that acute maternal hypercapnia caused MRI changes suggestive of acute placental hypoperfusion with fetal asphyxia and fetal brain sparing. This may be related to the observation that chronic maternal asphyxia led to increased HIF-1α expression in fetal liver but not fetal brain.

SOAP 2017