The anti-inflammatory compound candesartan cilexetil improves neurological outcomes in a mouse model of neonatal hypoxia

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Date
2019-07-24
Authors
Quinlan, Sean
Merino-Serrais, Paula
Di Grande, Alessandra
Dussmann, Heiko
Prehn, Jochen H. M.
Ní Chonghaile, Tríona
Henshall, David C.
Jimenez-Mateos, Eva M.
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Frontiers Media
Published Version
10.3389/fimmu.2019.01752
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Abstract
Recent studies suggest that mild hypoxia-induced neonatal seizures can trigger an acute neuroinflammatory response leading to long-lasting changes in brain excitability along with associated cognitive and behavioral deficits. The cellular elements and signaling pathways underlying neuroinflammation in this setting remain incompletely understood but could yield novel therapeutic targets. Here we show that brief global hypoxia-induced neonatal seizures in mice result in transient cytokine production, a selective expansion of microglia and long-lasting changes to the neuronal structure of pyramidal neurons in the hippocampus. Treatment of neonatal mice after hypoxia-seizures with the novel anti-inflammatory compound candesartan cilexetil suppressed acute seizure-damage and mitigated later-life aggravated seizure responses and hippocampus-dependent learning deficits. Together, these findings improve our understanding of the effects of neonatal seizures and identify potentially novel treatments to protect against short and long-lasting harmful effects.
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Keywords
Neonatal encephalopathy , Inflammation , Microglia , Seizures , Hypoxia
Citation
Quinlan, S., Merino-Serrais, P., Di Grande, A., Dussmann, H., Prehn, J. H. M., Ní Chonghaile, T., Henshall, D. C. and Jimenez-Mateos, E. M. (2019) 'The Anti-inflammatory Compound Candesartan Cilexetil Improves Neurological Outcomes in a Mouse Model of Neonatal Hypoxia', Frontiers in Immunology, 10, 1752 (15pp). doi: 10.3389/fimmu.2019.01752
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https://hdl.handle.net/10468/9379
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INFANT Research Centre - Journal Articles
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© 2019, Quinlan, Merino-Serrais, Di Grande, Dussmann, Prehn, Ní Chonghaile, Henshall and Jimenez-Mateos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.