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Brain Behav Immun. 2018 Mar;69:418-427. doi: 10.1016/j.bbi.2018.01.001. Epub 2018 Jan 31.

Mild prenatal hypoxia-ischemia leads to social deficits and central and peripheral inflammation in exposed offspring.

Author information

1
Irish Centre for Fetal and Neonatal Translational Research, Cork University Maternity Hospital, Cork, Ireland; Department of Obstetrics & Gynaecology, University College Cork (UCC), Cork, Ireland.
2
Irish Centre for Fetal and Neonatal Translational Research, Cork University Maternity Hospital, Cork, Ireland; Department of Pharmacology, School of Pharmacy, UCC, Cork, Ireland.
3
Irish Centre for Fetal and Neonatal Translational Research, Cork University Maternity Hospital, Cork, Ireland; Department of Paediatrics and Child Health, UCC, Cork, Ireland.
4
Irish Centre for Fetal and Neonatal Translational Research, Cork University Maternity Hospital, Cork, Ireland; Department of Anatomy and Neuroscience and Cork Neuroscience Centre, UCC, Cork, Ireland. Electronic address: g.okeeffe@ucc.ie.

Abstract

Hypoxic-ischemic encephalopathy (HIE) resulting from intrauterine or perinatal hypoxic-ischemia (HI) is a leading cause of long-term neonatal neurodisability. While most studies of long-term outcome have focused on moderate and severe HIE in term infants, recent work has shown that those with mild HIE may have subtle neurological impairments. However, the impact of mild HI on pre-term infants is much less clear given that pre-term birth is itself a risk factor for neurodisability. Here we show that mild HI insult alters behaviour, inflammation and the corticosterone stress response in a rat model of pre-term HIE. Mild HI exposure led to social deficits in exposed offspring at postnatal day 30, without impairments in the novel object recognition test nor in the open field test. This was also accompanied by elevations in circulating adrenocorticotropic hormone and corticosterone indicating an exaggerated stress response. There were also elevations in il-1β and il-6 but not tnf-α mRNA and protein in the brain and blood samples. In summary we find that a mild HI exposure leads to social deficits, central and peripheral inflammation, and an abnormal corticosterone response which are three core features of autism spectrum disorder. This shows that mild HI exposure may be a risk factor for an abnormal neurodevelopmental outcome in pre-term offspring.

KEYWORDS:

ASD; Autism; Corticosterone; HIE; Hypoxic-ischemic brain injury; Inflammation; Interleukin-6; Perinatal asphyxia; Stress

PMID:
29355822
DOI:
10.1016/j.bbi.2018.01.001
[Indexed for MEDLINE]

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