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Independence of extracellular tortuosity and volume fraction during osmotic challenge in rat neocortex

June Kume-Kick, TomásMazel*, Ivan Vorísek*, Sabina Hrabetová, Lian Tao and Charles Nicholson

The structural properties of brain extracellular space (ECS) are summarised by the tortuosity () and the volume fraction (). To determine if these two parameters were independent, we varied the size of the ECS by changing the NaCl content to alter osmolality of bathing media for rat cortical slices. Values of and were extracted from diffusion measurements using the real-time ionophoretic method with tetramethylammonium (TMA⁺). In normal medium (305 mosmol kg^-1), the average value of was 1.69 and of was 0.24. Reducing osmolality to 150 mosmol kg^-1, increased to 1.86 and decreased to 0.12. Increasing osmolality to 350 mosmol kg^-1, reduced to about 1.67 where it remained unchanged even when osmolality increased further to 500 mosmol kg^-1. In contrast, increased steadily to 0.42 as osmolality increased. Comparison with previously published experiments employing 3000 M_r dextran to measure , showed the same behaviour as for TMA⁺, including the same constant in hypertonic media but with a steeper slope in the hypotonic solutions. These data show that and behave differently as the ECS geometry varies. When decreases, increases but when increases, rapidly attains a constant value. A previous model allowing cellular shape to alter during osmotic challenge can account qualitatively for the plateau behaviour of .

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