Changes in extracellular space (ECS) diffusion parameters, DC potentials and extracellular potassium concentration were studied during single and repeated cortical spreading depressions (SD) in 13-15 (P13-15), 21 (P21) and 90-day-old (adult) Wistar rats. The real-time iontophoretic method using tetramethylammonium (TMA+)-selective microelectrodes was employed to measure three ECS parameters in the somatosensory cortex: the ECS volume fraction α (α = ECS volume/total tissue volume), ECS tortuosity λ (increase in diffusion path length) and the nonspecific TMA+ uptake k’. SD was elicited by needle prick. SD was significantly longer at P13-15 than at P21 and in adults. During SD, α in all age groups decreased from 0.21-0.23 to 0.05-0.09; λ increased from 1.55-1.65 to 1.95-2.07. Ten minutes after SD, α (in adults) and λ (all age groups) increased compared to controls. This increase persisted even 1 hour after SD. When SD was repeated at 1 hour intervals, both α and λ showed a gradual cumulative increase with SD repetition. Our study also shows that cortical SD is, as early as P13, accompanied by severe ECS shrinkage and increased diffusion path length (tortuosity) with values similar to adults, followed by a long-lasting increase in ECS volume and tortuosity when compared to pre-SD values., T. Mazel, F. Richter, L. Vargová, E. Syková., and Obsahuje bibliografii
The diffusion of neuroactive substances in the extracellular space (ECS) plays an important role in short- and long-distance communication between nerve cells and is the underlying mechanism of extrasynaptic (volume) transmission. The diffusion properties of the ECS are described by three parameters: 1. ECS volume fraction α (α = ECS volume/ total tissue volume), 2. tortuosity λ (λ2 = free /apparent diffusion coefficient), reflecting the presence of diffusion barriers represented by, e.g., fine neuronal and glial processes or extracellular matrix molecules and 3. nonspecific uptake k’. These diffusion parameters differ in various brain regions, and diffusion in the CNS is therefore inhomogeneous. Moreover, diffusion barriers may channel the migration of molecules in the ECS, so that diffusion is facilitated in a certain direction, i.e. diffusion in certain brain regions is anisotropic. Changes in the diffusion parameters have been found in many physiological and pathological states in which cell swelling, glial remodeling and extracellular matrix changes are key factors influencing diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect the accumulation and diffusion of neuroactive substances in the CNS and thus extrasynaptic transmission, neuron-glia communication, transmitter „spillover“ and synaptic cross-talk as well as cell migration, drug delivery and treatment., L. Vargová, E. Syková., and Obsahuje bibliografii a bibliiografické odkazy