Heterogeneous and anisotropic diffusion in the developing rat spinal cord

Abstract

Extrasynaptic transmission is mediated by the diffusion of transmitters, through the extracellular space (ECS) to receptors on neurons and glia. The three-dimensional diffusion of tetramethylammonium (mol. wt 74.1 kDa) was investigated in the isolated rat spinal cord at postnatal days 4-20. The diffusion parameters of the ECS, volume fraction alpha, tortuosity lambda (lambda2 = free/apparent diffusion coefficient in tissue) and nonspecific uptake k', were different in gray and white matter. In both gray and white matter, alpha decreased with neuronal development and gliogenesis by about 15% while lambda significantly increased. Diffusion in gray matter remained isotropic (lambda = 1.65), while in white matter it became anisotropic, i.e. easier along the fibers (lambda = 1.38) than across the fibers (lambda = 1.80). Anisotropy increased in the second postnatal week, during pronounced myelination. In myelinated tissue, preferential diffusion of neuroactive substances occurs along the axons.

Bral1: Its Role in Diffusion Barrier Formation and Conduction Velocity in the CNS

“…ECM mol-ecules play a role in tissue cytoarchitecture by maintaining the optimal size of intercellular pores and by creating diffusion barriers (Roitbak and Syková, 1999;Zámecník et al, 2004;Syková et al, 2005). Diffusion barriers formed by myelin sheaths, glial processes and the ECM may channel the diffusion of molecules in a certain direction, so that diffusion is anisotropic, i.e., unequal along different axes (Prokopová et al, 1997;Vorísek and Syková, 1997). Since changes in the ECS diffusion parameters and anisotropy significantly affect the accumulation and diffusion of neuroactive substances (Syková, 2004;Syková and Vargová, 2008), it appears that ECM assembly in the extranodal spaces may affect saltatory conduction.…”

Glial Cells, Glutamate & the Hippocampus

“…We conclude: (1) in the frog SC diffusion parameters do not differ from those seen in mammals (Prokopova et al 1997). (2) In the FT a was larger and A lower than in the SC, presumably due to a lower density of cellular elements in the FT. (3) In elevated K+, but not in hypotonic solution, a significantly higher decrease in a was found in SC than in FT, while a higher increase in A was found in FT than in SC.…”

Serotonin Concentrations in the Lumbosacral Spinal Cord of the Adult Rat Following Microinjection or Dorsal Surface Application

“…Spread of 5-HT within the gray matter was examined in the rostrocaudal plane, and assumed to be equal in all directions (Prokopová et al 1997). In these experiments (seven animals), the tips of the CFMEs were spaced 400 -2,800 m from the tip of the drug micropipette, at the same depth and lamina in the lumbosacral spinal cord.…”

“…Changes in extracellular space diffusion parameters occur over the first couple of postnatal weeks, including a decrease in the extracellular space volume fraction, an increase in tortuosity, and an increase in anisotropy with the appearance of myelin (Prokopová et al 1997;Syková and Chvátal 1993). Last, developmental changes occur in the pia-arachnoidal membranes over the first three postnatal weeks, resulting in an increase in the amount of extracellular collagenous and elastic fibers (McLone and Bondareff 1975).…”

“…In the microinjection protocol, multiple CFMEs measured the spread of 5-HT only in the rostral-caudal direction after it was delivered into a focal area of the cord. Based on previously published work on diffusion characteristics within the spinal cord (Prokopová et al 1997;Š imonová et al 1996), we assumed that the spread of 5-HT from a point source was essentially the same in all directions. In the bath superfusion protocol, CFMEs were positioned at different depths but at a similar medial-lateral and rostral-caudal position in each experiment so that they would measure the dorsal-ventral spread of a continuous supply of 5-HT after it was rapidly applied to the dorsal surface of the cord.…”