The anti-inflammatory compound candesartan cilexetil improves neurological outcomes in a mouse model of neonatal hypoxia
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.
Science Foundation Ireland (13/SIRG/2114 and 12/RC/2272) and 16/RC/3948 co-funded under the European Regional Development Fund
FutureNeuro industry partners. SSMF postdoctoral Fellow (2015)
Ministerio de Ciencia, Innovacion y Universidades- Juan de la Cierva Incorporacion Fellow (IJCI-2016-27658)
CommentsThe original article is available at https://www.frontiersin.org/
Published CitationQuinlan S. et al. The anti-inflammatory compound candesartan cilexetil improves neurological outcomes in a mouse model of neonatal hypoxia. Front Immunol. 2019;10:1752.
Publication Date24 July 2019
- FutureNeuro Centre
- Physiology and Medical Physics
PublisherFrontiers Research Foundation
- Published Version (Version of Record)