Public Defence: Didrik Bakke Dukefoss

Cand.med. Didrik Bakke Dukefoss at Institute of Basic Medical Sciences will be defending the thesis “Roles of Astroglia in Cortical Spreading Depression” for the degree of PhD (Philosophiae Doctor).

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Photo: Simen Ringen.

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Trial Lecture – time and place

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Adjudication committee

  • First opponent: Professor Martin Lauritzen, University of Copenhagen
  • Second opponent: Associate Professor Sabina Hrabetova, SUNY Downstate Health Sciences University
  • Third member and chair of the evaluation committee: Professor Mona Elisabeth Skjelland, University of Oslo

Chair of the Defence

Associate Professor Jan Magnus Aronsen, Faculty of Medicine, University of Oslo

Principal Supervisor

Associate Professor Rune Enger, Faculty of Medicine, University of Oslo

Summary

This thesis, within the field of neuroscience, examines the role of glial cells in cortical spreading depression (CSD). CSD is a slow wave of complete depolarization of the cells in the cerebral cortex and causes a grave, transient disruption of the well-regulated homeostasis that the brain depends on to function. Moreover, CSD is characterized by cellular swelling as well as by extracellular overflow of the neurotransmitter glutamate, which may be neurotoxic.

CSD is widely accepted as the underlying mechanism of migraine aura. Some migraine patients experience aura phenomena, which in most cases include sensory disturbances that precede the headache onset. CSD-like phenomena also occur in a range of neurological conditions, including epilepsy, ischemic and hemorrhagic stroke, and traumatic brain injury. 

The glial cell subtype astrocytes serve important homeostatic functions in the CNS, including maintenance of the ion composition in the extracellular environment, uptake and conversion of neurotransmitters, and control of the extracellular volume fraction. We hypothesized that the water channel AQP4 and the potassium channel Kir4.1, both abundant in the astrocytic cell membrane, affect the extracellular glutamate dynamics during CSD. We also hypothesized that astrocytic endfeet, that enwrap cerebral vasculature, swell during CSD and thereby obstruct waste clearance that occurs via perivascular spaces.

To address the questions we asked, we employed transgenic mouse lines in combination with genetically encoded fluorescent nanosensors and two-photon microscopy. 

This thesis concludes that both AQP4 and Kir4.1 play a significant role in determining the glutamate dynamics in the aftermath of CSD. These findings introduce the two channels as candidates for therapeutic intervention. Moreover, the thesis also presents evidence that astrocytic endfeet undergo robust swelling after passage of a CSD, but too briefly to vitally hinder brain waste clearance.

Additional information

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Published Aug. 5, 2022 11:35 AM - Last modified Aug. 15, 2022 12:31 PM