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Real-time Iontophoresis with Tetramethylammonium to Quantify Volume Fraction and Tortuosity of Brain Extracellular Space
Published on: July 24, 2017
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In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity.
A Ledo1, E Fernandes2, A Salvador3
1Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal.
Redox Biology
|February 1, 2022
Summary
Hydrogen peroxide (H₂O₂) acts as a signaling molecule in the brain. Its rapid diffusion and short half-life suggest it functions like a volume neurotransmitter, influencing brain networks.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Hydrogen peroxide (H₂O₂) is recognized as a key redox signaling molecule.
- Its role as an intercellular signaling molecule and neuromodulator in the brain is increasingly evident.
- H₂O₂ influences neuronal polarity, connectivity, synaptic transmission, and network tuning.
Purpose of the Study:
- To investigate the extracellular concentration dynamics of H₂O₂ in the brain.
- To determine the factors affecting H₂O₂ diffusion patterns and half-life in brain tissue.
- To quantitatively characterize H₂O₂'s behavior as a potential volume neurotransmitter.
Main Methods:
- Utilized a novel microsensor for measuring H₂O₂ concentration dynamics.
- Experiments were conducted in both ex vivo rodent brain slices and in vivo models.
- Measured H₂O₂ concentration, diffusion coefficient, and half-life in the brain extracellular matrix.
Main Results:
- Exogenously applied H₂O₂ has an average in vivo half-life of 2.2 seconds.
- The effective in vivo diffusion coefficient of H₂O₂ was determined to be 2.5 × 10⁻⁵ cm²/s.
- H₂O₂ can diffuse over 100 μm in the extracellular space within its half-life.
Conclusions:
- H₂O₂ exhibits characteristics of a volume neurotransmitter, connecting diverse cell types in the brain.
- These quantitative findings provide insights into redox signaling physiology.
- Understanding H₂O₂ dynamics is crucial for addressing redox homeostasis in disease states.

