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Hepatic acute phase response protects the brain from focal inflammation during postnatal window of susceptibility

Sá-Pereira, I; Roodselaar, J; Couch, Y; Consentino Kronka Sosthenes, M; Evans, M C; Anthony, D C; Stolp, H B

Authors

I Sá-Pereira

J Roodselaar

Y Couch

M Consentino Kronka Sosthenes

M C Evans

D C Anthony

H B Stolp



Abstract

Perinatal inflammation is known to contribute to neurodevelopmental diseases. Animal models of perinatal inflammation have revealed that the inflammatory response within the brain is age dependent, but the regulators of this variation remain unclear. In the adult, the peripheral acute phase response (APR) is known to be pivotal in the downstream recruitment of leukocytes to the injured brain. The relationship between perinatal brain injury and the APR has not been established. Here, we generated focal inflammation in the brain using interleukin (IL)-1β at postnatal day (P)7, P14, P21 and P56 and studied both the central nervous system (CNS) and hepatic inflammatory responses at 4 h. We found that there is a significant window of susceptibility in mice at P14, when compared to mice at P7, P21 and P56. This was reflected in increased neutrophil recruitment to the CNS, as well as an increase in blood–brain barrier permeability. To investigate phenomena underlying this window of susceptibility, we performed a dose response of IL-1β. Whilst induction of endogenous IL-1β or intercellular adhesion molecule (ICAM)-1 in the brain and induction of a hepatic APR were dose dependent, the recruitment of neutrophils and associated blood–brain barrier breakdown was inversely proportional. Furthermore, in contrast to adult animals, an additional peripheral challenge (intravenous IL-1β) reduced the degree of CNS inflammation, rather than exacerbating it. Together these results suggest a unique window of susceptibility to CNS injury, meaning that suppressing systemic inflammation after brain injury may exacerbate the damage caused, in an age-dependent manner.

Citation

Sá-Pereira, I., Roodselaar, J., Couch, Y., Consentino Kronka Sosthenes, M., Evans, M. C., Anthony, D. C., & Stolp, H. B. (2018). Hepatic acute phase response protects the brain from focal inflammation during postnatal window of susceptibility. Brain, Behavior, and Immunity, https://doi.org/10.1016/j.bbi.2018.01.008

Journal Article Type Article
Acceptance Date Jan 16, 2018
Publication Date Jan 31, 2018
Deposit Date Mar 3, 2018
Publicly Available Date Mar 3, 2018
Journal Brain, Behavior, and Immunity
Print ISSN 0889-1591
Publisher Elsevier
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1016/j.bbi.2018.01.008
Public URL https://rvc-repository.worktribe.com/output/1388980

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