Significant shrinkage of extracellular space during global cerebral ischemia: differences in gray and white matter ischemia

Abstract

Brain extracellular space (ECS) provides an important microenvironment for neurons and glial cells. In the present study, we investigated differences in ischemic changes of ECS in gray and white matter during global ischemia in cats (n = 8). Diffusion capacity of tetramethylammonium ion (TMA⁺, 74.1Da) was evaluated by measuring extracellular TMA⁺ concentration applied via microdialysis. In both gray and white matter, TMA⁺ concentration significantly increased within 10 minutes after the induction of ischemia, and sustained during 120 min of ischemia. The increase, however, was slower and smaller in white matter than in gray matter. In other two animals, volume fraction and tortuosity of ECS were determined by iontophoresis during global ischemia. After 30 min of ischemia induction, volume fraction was decreased and tortuosity was increased in both gray and white matter. In white matter, decrease in volume fraction and increase in tortuosity were smaller than in gray matter. The present study demonstrates that cerebral ischemia induces not only significant shrinkage of ECS volume but also restricts molecular diffusion within. Smaller changes of diffusion capacity within white matter ECS during ischemia may be relevant for lower ischemic vulnerability of the region.