Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Miriam Echevarría Irusta, Hospital Universitario Virgen del Rocío, Spain
- Second opponent: Research team manager Malin Wennström, Lund University, Sweden
- Third member and chair of the evaluation committee: Associate professor Jean-Luc Boulland, University of Oslo
Chair of the Defence
Professor Svend Davanger, University of Oslo
Principal Supervisor
Professor Mahmood Reza Amiry-Moghaddam, University of Oslo
Summary
Astrocytes are star-shaped cells that play crucial roles in the central nervous system (CNS). Their endfeet envelop the vascular network of the CNS, contributing to the regulation of the blood-brain barrier, cerebral blood flow, nutrient transport, and waste removal.
Aquaporin-4 (AQP4) is the main water channel protein in the CNS, densely expressed in the endfeet of astrocytes. It plays a critical role in maintaining water homeostasis in the CNS. AQP4 has been extensively studied for its role in the development of cerebral edema and the regulation of extracellular space volume. In the past decade, research has uncovered new functions of AQP4. This thesis specifically investigates the potential pro-inflammatory role of AQP4 beyond its role in edema formation, its possible involvement in diurnal regulation of the glymphatic system, and its proposed impact on age-related neurodegenerative diseases.
We found that deletion of AQP4 is protective in certain type of ischemic stroke characterized by relatively small infarct size and limited edema formation, as AQP4 deficient mice exhibited reduced infarction. We also observed that AQP4 is involved in astrocyte reactivity following ischemic stroke, with increased astrocytic activation in AQP4 deficient mice. Furthermore, our results demonstrate that diurnal differences in glymphatic function are independent of AQP4 expression. We also observed an age-dependent increase in AQP4 expression in the neuropil, accompanied by possible changes in its perivascular polarization.
We concluded that AQP4 does not play a pro-inflammatory role one week after stroke, and its role in inflammation is context-dependent. Moreover, its expression and localization are not subject to circadian rhythms. There are indications of possible changes in the localization and expression of AQP4 with aging. This work highlights AQP4's role in stroke, astrocyte reactivity, aging, and inflammation, offering new insights for targeting it in neurological therapy.
Additional information
Contact the research support staff.