Extracellular diffusion is fast and isotropic in the stratum radiatum of hippocampal CA1 region in rat brain slices

Publisher Website
Google Scholar
Abstract
Molecular transport in brain extracellular space (ECS) is hindered by the structure of the tissue. Diffusion analysis of small extracellular markers quantifies tissue hindrance, expressed as tortuosity λ = (D/D*)1/2, where D is the free diffusion coefficient and D* is the effective diffusion coefficient in tissue. In healthy brain, λ is ≈1.6, but the nature of this parameter is poorly understood. We report that the stratum radiatum of the hippocampal CA1 region in vitro, previously shown to be anisotropic (i.e., different along the x-, y-, and z-axes) in in vivo study, is isotropic like somatosensory neocortex but has a reduced λ. Diffusion of fluorophore-labeled dextran (f-dex, Mr 3,000) and tetramethylammonium (TMA+, Mr 74) was measured in rat brain slices (400 μm) using integrative optical imaging (IOI) and real-time iontophoresis (RTI), respectively. In the stratum radiatum, diffusion of f-dex was similar along the x-, y-, and z-axes (λx, λy; λz were 1.55, 1.53, and 1.55), but the tortuosity was significantly lower than in the neocortex, where λ = 1.81. This finding was confirmed by the RTI method, which measured λ with TMA+, a much smaller molecule, and determined volume fraction α, the proportion of tissue occupied by the ECS. In stratum radiatum, λx, λy, and λz were 1.47, 1.44, and 1.46, while in neocortex, λ was 1.65. The ECS volume fraction was similar (0.24) in both regions. It is proposed that in the hippocampus, low λ reflects a reduced occurrence of concave extracellular microdomains, referred to as dead spaces, which increase tortuosity by transient trapping of markers. Functionally, a low λ may permit structural plasticity and facilitate extrasynaptic communication. It may also enhance the spread of neuroactive substances and thus contribute to the sensitivity of the hippocampal CA1 region to ischemia and epilepsy.