Publications by authors named "I Georgakoudi"

Neuron-glial cell interactions following traumatic brain injury (TBI) determine the propagation of damage and long-term neurodegeneration. Spatiotemporally heterogeneous cytosolic and mitochondrial metabolic pathways are involved, leading to challenges in developing effective diagnostics and treatments. An engineered three-dimensional brain tissue model comprising human neurons, astrocytes, and microglia is used in combination with label-free, two-photon imaging and microRNA studies to characterize metabolic interactions between glial and neuronal cells over 72 hours following impact injury.

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Brain metabolism is essential for the function of organisms. While established imaging methods provide valuable insights into brain metabolic function, they lack the resolution to capture important metabolic interactions and heterogeneity at the cellular level. Label-free, two-photon excited fluorescence imaging addresses this issue by enabling dynamic metabolic assessments at the single-cell level without manipulations.

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In this paper, we present a 2-photon imaging probe system featuring a novel fluorescence collection method with improved and reliable efficiency. The system aims to miniaturize the potential of 2-photon imaging in the metabolic and morphological characterization of cervical tissue at sub-micron resolution over large imaging depths into a flexible and clinically viable platform towards the early detection of cancers. Clinical implementation of such a probe system is challenging due to inherently low levels of autofluorescence, particularly when imaging deep in highly scattering tissues.

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Article Synopsis
  • Two-photon microscopy (2PM) is being studied as a non-invasive technique for detecting high-grade cervical precancerous lesions by assessing tissue metabolism and structure in detail.* -
  • The study involved analyzing 62 cervical biopsies and using advanced image analysis to achieve a high sensitivity (90.8%) and specificity (72.3%) for identifying high-grade squamous intraepithelial lesions (HSILs), even with only two images taken from different tissue depths.* -
  • Results showed that the presence of HSILs was associated with metabolic changes, such as increased glycolysis and fatty acid metabolism, indicating that 2PM could be a valuable tool for clinical evaluation of cervical precancers.*
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Article Synopsis
  • Mitochondrial fatty acid oxidation (FAO) is crucial for the self-renewal of hematopoietic stem cells (HSCs), with a significant role in their cellular metabolism.
  • HSCs contain the highest levels of mitochondrial NADPH, which is necessary for maintaining their fate and homeostasis, primarily by supporting cholesterol synthesis.
  • Disrupting FAO affects the distribution of mitochondrial NADPH in daughter cells during HSC division, demonstrating that the FAO-NADPH-cholesterol pathway is essential for the formation of extracellular vesicles, which in turn is vital for HSC self-renewal and overall blood cell production.
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