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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Michael Kirschfink, Heidelberg University, Germany
- Second opponent: Postdoctoral Researcher Anne Rosbjerg, University of Copenhagen, Denmark
- Third member and chair of the evaluation committee: Professor Guttorm Haraldsen, University of Oslo
Chair of the Defence
Professor II Per Steinar Halvorsen, University of Oslo
Principal Supervisor
Researcher Søren Erik Pischke, University of Oslo
Summary
Acute brain injury and cardiac arrest are the number one causes of death and disabilities that occur every year in the world. Over half of the patients develop long-term complications and have lower survival rates over a long period compared to healthy controls. The common hallmark for both conditions is a temporal disturbance of blood flow locally or systemically, causing ischemia that leads to cell death. The reperfusion period upon treatment leads to an aggravation of organ damage. This phenomenon is called Ischemia/Reperfusion injury (IRI). IRI is known to impact cellular metabolism and may lead to the activation of inflammatory mechanisms.
The aim of this thesis was to investigate the impact of innate immunity in general and, in particular, complement activation in the course of local IRI (mild traumatic brain injury) and systemic IRI (cardiac arrest). In addition, we aimed for improving the diagnostic strategy of complement activation measurement in patients with acute medical conditions and possible treatment by hypothermia.
We found that activation of the innate immune system was not limited to an acute incidence but was induced over a one-year period, even after a relatively mild sterile head injury. Likewise, complement system activation was increased in resuscitated cardiac arrest patients and associated with poor clinical outcome. We found that measurement of relatively stable complement activation marker sC5b-9 is sufficient and sensitive in detecting complement activation in acute medical situations and can be suggested when complement inhibitor prescription verification is required. Last, temperature should be considered as an active intervention limiting complement activation and inflammation and might be used in situations where low temperatures are possible to obtain as e.g., organ transplantation.
This thesis has several conclusions, but all highlight that the innate immune response and in particular, the complement system should be understood and targeted as upstream recognition systems at the frontline of defense and may serve as basis for future clinical intervention studies.
Additional information
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