Trial lecture - time and Place
See trial lecture.
Adjudication committee
- 1st opponent: Professor Eleanor J. Molloy, University of Dublin
- 2nd opponent: Professor Rashmin Savani, University of Texas Southwestern Medical Center
- Committee chair: Associate Professor Kjetil Wessel Andressen, University of Oslo
Chair of the defence
Professor II Erik Thaulow,
Principal Supervisor
Professor Emeritus Ola Didrik Saugstad,
Summary
Innate immune response in neonatal hypoxic-ischemic brain injury
Hypoxic-ischemic brain injury is a major contributor to neonatal mortality and morbidity. After such insults, the innate immune system responds swiftly and is central in the pathogenesis. A well balanced immune response is necessary to reduce the impact and resolve damaged tissue. However, an under or over stimulated response can potentially worsen the outcome.
In the thesis «Innate immune response in neonatal hypoxic-ischemic brain injury», Martin B. Ystgaard and colleagues investigated the role of a central component of the innate immune response, namely NLRP3, using knockout mice and piglets.
The NLRP3 inflammasome consists of three parts, NLRP3, ASC and procaspase-1. Upon activation, it serves as a key regulator of the pro inflammatory cytokines interleukin (IL)-1β and IL-18. NLRP3 deficient, ASC deficient and wild type mice, 9 days old, underwent left common carotid artery ligation, followed by 1 hour hypoxia with 10% oxygen. After 1 week, brains were harvested. We found that NRLP3 deficiency aggravates brain injury, while ASC deficiency ameliorates brain injury following neonatal hypoxic-ischemic brain injury.
Furthermore we investigated the role of a newly developed anti-inflammatory drug, N-acetylcysteine amide (NACA), in a piglet model of neonatal hypoxic-ischemic brain injury. Piglets treated with NACA showed reduced levels of IL-1β and a steeper decline in tumor necrosis factor-α. There were however no significant difference in brain injury following NACA treatment.
We conclude that deficiency of central components of the innate immune system can both aggravate injury such as NLRP3 deficiency, and on the other hand ameliorate injury, such as ASC deficiency following neonatal hypoxic-ischemic brain injury. NACA can serve a potential neuroprotective role by dampening the inflammatory response.
Additional information
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