An unexpected decrease of extracellular space (ECS) tortuosity was recently reported in thick (1,000 microm) ischemic slices using radiotracers. The current study shows that the tortuosity in thick slices from rat neocortex can increase or decrease depending on experimental conditions, whereas ECS volume fraction remains diminished to approximately 10%. Using diffusion of tetramethylammonium, it was found that tortuosity rose from a normoxic value of 1.66 to 1.99 in thick slices. However, tortuosity dropped to 1.54 when dextran (70,000 molecular weight) was added to the bathing medium. The current results show that dextran enhances diffusion in thick ischemic slices without increasing the size of the ECS.