Ultrasound Imaging of Mouse Fetal Intracranial Hemorrhage Due to Ischemia/Reperfusion

Abstract

Despite vast improvement in perinatal care during the 30 years, the incidence rate of neonatal encephalopathy remains unchanged without any further Progress towards preventive strategies for the clinical impasse. Antenatal brain injury including fetal intracranial hemorrhage caused by ischemia/reperfusion is known as one of the primary triggers of neonatal injury. However, the mechanisms of antenatal brain injury are poorly understood unless better predictive models of the disease are developed. Here we show a mouse model for fetal intracranial hemorrhage in vivo developed to investigate the actual timing of hypoxia-ischemic events and their related mechanisms of injury. Intrauterine growth restriction mouse fetuses were exposed to ischemia/reperfusion cycles by occluding and opening the uterine and ovarian arteries in the mother. The presence and timing of fetal intracranial hemorrhage caused by the ischemia/reperfusion were measured with histological observation and ultrasound imaging. Protein-restricted diet increased the risk of fetal intracranial hemorrhage. The monitoring of fetal brains by ultrasound B-mode imaging clarified that cerebral hemorrhage in the fetal brain occurred after the second ischemic period. Three-dimensional ultrasound power Doppler imaging visualized the disappearance of main blood flows in the fetal brain. These indicate a breakdown of cerebrovascular autoregulation which causes the fetal intracranial hemorrhage. This study supports the fact that the ischemia/reperfusion triggers cerebral hemorrhage in the fetal brain. The present method enables us to noninvasively create the cerebral hemorrhage in a fetus without directly touching the body but with repeated occlusion and opening of the uterine and ovarian arteries in the mother.

Relationship Between Short Term Variability (STV) and Onset of Cerebral Hemorrhage at Ischemia–Reperfusion Load in Fetal Growth Restricted (FGR) Mice

“…They found that the STV tended to decrease compared with that in the control group. Moreover, they demonstrated that these fetuses were at high risk of cerebral hemorrhage upon ischemia–reperfusion loading ( Funamoto et al, 2017 ).…”

Microfluidic platform for the reproduction of hypoxic vascular microenvironments

“…These results indicate that the collective migration and morphological changes of ECs could be dependent on the decrease of VE-cadherin expression by the hypoxic exposure. An ischemia–reperfusion event reportedly causes transient hypoxia and reoxygenation, as well as variations in fluid shear stress, and triggers the production of toxic substances such as reactive oxygen species, leading to disorders such as organ dysfunction and hemorrhage 40 . In order to establish prevention methods for these conditions, the developed microfluidic platform will be a useful tool for elucidating the cellular dynamics of ECs in response to hypoxic and flow exposure.…”