Time-resolved quantification of the dynamic extracellular space in the brain during short-lived event: methodology and simulations

Journal of Neurophysiology
Kevin C ChenHui-Hui Zhao

Abstract

Two macroscopic parameters describe the interstitial diffusion of substances in the extracellular space (ECS) of the brain, the ECS volume fraction α and the diffusion tortuosity λ. Past methods based on sampling the extracellular concentration of a membrane-impermeable ion tracer, such as tetramethylammonium (TMA+), can characterize either the dynamic α(t) alone or the constant α and λ in resting state but never the dynamic α(t) and λ(t) simultaneously in short-lived brain events. In this work, we propose to use a sinusoidal method of TMA+ to provide time-resolved quantification of α(t) and λ(t) in acute brain events. This method iontophoretically injects TMA+ in the brain ECS by a sinusoidal time pattern, samples the resulting TMA+ diffusion waveform at a distance, and analyzes the transient modulations of the amplitude and phase lag of the sampled TMA+ waveform to infer α(t) and λ(t). Applicability of the sinusoidal method was verified through computer simulations of the sinusoidal TMA+ diffusion waveform in cortical spreading depression. Parameter sensitivity analysis identified the sinusoidal frequency and the interelectrode distance as two key operating parameters. Compared with other TMA+-based methods, the sinusoidal me...Continue Reading

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Methods Mentioned

BETA
biosensor

Software Mentioned

LabView
DSS

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