Diffusion properties of the brain in health and disease

Extrasynaptic transmission between neurons and communication between neurons and glia are mediated by the diffusion of neuroactive substances in the extracellular space (ECS)—volume transmission. Diffusion in the CNS is inhomogeneous and often not uniform in all directions (anisotropic). Ionic chang...

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Bibliographic Details
Published in:Neurochemistry international 2004-09, Vol.45 (4), p.453-466
Main Author: Sykova, E
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Anisotropy
Apparent diffusion coefficient
Brain - physiology
Diffusion
Diffusion-weighted NMR
Extracellular matrix
Extracellular Space - physiology
Humans
Synaptic Transmission - physiology
Thermodynamics
Tortuosity
Volume fraction
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Summary:Extrasynaptic transmission between neurons and communication between neurons and glia are mediated by the diffusion of neuroactive substances in the extracellular space (ECS)—volume transmission. Diffusion in the CNS is inhomogeneous and often not uniform in all directions (anisotropic). Ionic changes and amino acid release result in cellular (particularly glial) swelling, compensated for by ECS shrinkage and a decrease in the apparent diffusion coefficients of neuroactive substances or water (ADC W). The diffusion parameters of the CNS in adult mammals (including humans), ECS volume fraction α ( α=ECS volume/total tissue volume; normally 0.20–0.25) and tortuosity λ ( λ 2= D/ADC; normally 1.5–1.6), hinder the diffusion of neuroactive substances and water. A significant decrease in ECS volume and an increase in diffusion barriers (tortuosity) and anisoptropy have been observed during stimulation, lactation or learning deficits during aging, due to structural changes such as astrogliosis, the re-arrangement of astrocytic processes and a loss of extracellular matrix. Decreases in the apparent diffusion coefficient of tetramethylammonium (ADC TMA) and ADC W due to astrogliosis and increased proteoglycan expression were found in the brain after injury and in grafts of fetal tissue. Tenascin-R and tenascin C-deficient mice also showed significant changes in ADC TMA and ADC W, suggesting an important role for extracellular matrix molecules in ECS diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect neuron-glia communication, the spatial relation of glial processes towards synapses, the efficacy of glutamate or GABA ‘spillover’ and synaptic crosstalk, the migration of cells, the action of hormones and the toxic effects of neuroactive substances and can be important for diagnosis, drug delivery and new treatment strategies.
ISSN:0197-0186
1872-9754
DOI:10.1016/j.neuint.2003.11.009