Time-resolved quantification of the dynamic extracellular space in the brain: study of cortical spreading depression

摘要

Extracellular diffusion in the brain is customarily characterized by two parameters, the extracellular space (ECS) volume fraction alpha and the diffusion tortuosity lambda. How these two parameters are temporarily modified and correlated in a physiological/pathological event remains unclear to date. Using tetramethylammonium (TMA(+)) as an ECS ion tracer in a newly updated iontophoretic sinusoidal method, we studied in this work the dynamic alpha(t) and lambda(t) in rat somatosensory cortex during spreading depression (SD). Temporal variations of alpha(t) and lambda(t), as evoked by SD, were obtained through analyses of the extracellular TMA(+) diffusion waveform resulting from a sinusoidally modulated point source. Most of the time, cortical SD induced coordinated alpha(t) decreases and lambda(t) increases. In rare occasions, SD induced sole decreases of alpha(t) with no changes in lambda(t). The independent modulation of alpha(t) and lambda(t) was neither associated with cortical anatomy nor with the specific shape of the SD field potential wave. Changes of alpha(t) and lambda(t) often took place acutely at the onset of SD, followed by a more transient modulation. Compared with the prior iontophoretic methods of TMA(+), the sinusoidal method provides time-resolved quantification of alpha(t) and lambda(t) in relative terms but also raises a higher property requirement on the TMA(+)-selective micro-electrode. The sinusoidal method could become a valuable tool in the studies of the dynamic ECS response in various brain events.