The effects of vascular intrauterine growth retardation on cortical astrocytes

Abstract

Objective. We sought to determine the pathogenesis of neurodevelopmental impairments in survivors of intrauterine growth retardation (IUGR).

Methods. We used an experimental rabbit vascular IUGR model. We ligated 25% of uteroplacental vessels (partial ischemia) of one-half of the fetuses on day 25 at the end of the third trimester. We then determined hemispheral DNA and protein levels, and used glial fibrillary acidic protein (GFAP) staining to count the labeled astrocytes at the superficial cortical layers.

Results. Ischemic fetuses were significantly smaller than control fetuses and presented a disproportionately small body and a relatively larger head compared with the normal body/head ratio, confirming the study model as that of asymmetric IUGR. Hemispheral DNA was unchanged in IUGR fetuses, but they had decreased brain weight, hemispheral protein content, and a reduced number of mature (GFAP-positive) cortical astrocytes compared with control fetuses.

Conclusion. Vascular IUGR, as demonstrated in our asymmetric IUGR model, adversely affected brain growth, cell size, and cortical astrocytes maturation. In view of the neurotrophic and neuroprotective functions of astrocytes, a reduced number of mature astrocytes during this critical period of development may be implicated in the pathogenesis of the neurodevelopmental impairments observed in IUGR.

Keywords:

• IUGR
• asymmetric
• vascular
• astrocytes
• rabbit
• model
• outcome

Acknowledgements

This study was supported by the Israel Ministry of Health, Chief Scientist's Office, the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, and the Gulton Foundation, New York, USA. Haim Bassan is supported by the Tel Aviv Sourasky research fund. Illana Gozes and Shaul Harel contributed equally to this work. Esther Eshkol is thanked for editorial assistance.