Medizinische Universität Graz - Research portal
Selected Publication:
Ramadani, P.
Correlative Light and Electron Microscopy of Magnetic Nanoparticle-Induced Stroke
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 99
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- Authors Med Uni Graz:
- Advisor:
- Malli Roland
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- Abstract:
- In 2016, stroke was the second most common cause of mortality worldwide. In recent years, the number of disabilities associated with stroke has increased significantly. The therapy outcomes are very unsatisfactory. One major reason is that much of the pathophysiology of stroke remains unknown. Scientists have developed various methods to a gain better understanding of the processes, but many have big limitations. To better understand what happens after a stroke, methods are needed that can trace the pathophysiological processes over time and create images with very high resolution at the same time. Nanoparticles have gained more and more attention in recent years, due to their versatile uses and low toxicity in living organisms. They are used as drug carriers to deliver substances to the desired location for therapy. Iron oxide nanoparticles have multiple characteristic properties that have been combined in this work to develop a method for stroke induction and correlative light and electron microscopy. They are ferromagnetic and can be used to induce targetable, reproducible, focal stroke in vivo with selective reperfusion. In addition, they can be excited and can be visualized in the 2-photon microscope. Furthermore, they are easily detectable in the electron microscope due to their very dark appearance and can therefore act as correlation landmarks for correlative light and electron microscopy. The method was applied on a mouse to create a z-stack of electron microscopy images of a disrupted microvessel after a stroke. Fluorescent lipid nanoparticles were used to observe the dynamics of lipid nanoparticles in the brain after stroke. The analysis and 3D reconstruction revealed a hole in an endothelial cell with an invagination of extravascular content, causing vessel constriction. Deformed erythrocytes and immune response of microglia were also observed. Additionally, lipid nanoparticles were seen exiting the vessel through an intact blood-brain barrier via transcytosis. The method introduced here can be used to investigate the pathophysiological processes of stroke in high detail.