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Mild prenatal hypoxia-ischemia leads to social deficits and central and peripheral inflammation in exposed offspring
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Accepted Version
Date
2018-03-14
Authors
O'Driscoll, David J.
Felice, Valeria D.
Kenny, Louise C.
Boylan, Geraldine B.
O'Keeffe, Gerard W.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Published Version
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.
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Keywords
ASD , Autism , Corticosterone , HIE , Hypoxic-ischemic brain injury , Inflammation , Interleukin-6 , Perinatal asphyxia , Stress
Citation
O'Driscoll, D. J., Felice, V. D., Kenny, L. C., Boylan, G. B. and O'Keeffe, G. W. (2018) 'Mild prenatal hypoxia-ischemia leads to social deficits and central and peripheral inflammation in exposed offspring', Brain Behavior and Immunity, 69, 418-427. doi:10.1016/j.bbi.2018.01.001