Astrocytes, oligodendroglia, extracellular space volume and geometry in rat fetal brain grafts

Fetal neocortex or tectum transplanted to the midbrain or cortex of newborn rats develops various degrees of gliosis, i.e. increased numbers of hypert rophied, glial fibrillary acidic protein-positive astrocytes. In addition, there were patches or bundles of myelinated fibres positive for the oligode ndrocyte and central myelin marker Rip, and increased levels of extracellul ar matrix molecules. Three diffusion parameters-extracellular space volume fraction alpha (alpha = extracellular volume/total tissue volume), tortuosi ty lambda (lambda = root D/ADC, where D is the free and ADC is the apparent tetramethylammonium diffusion coefficient) and non-specific uptake k'-were determined in vivo from extracellular concentration-time profiles of tetra methylammonium. Grafts were subsequently processed immunohistochemically to compare diffusion measurements with graft morphology. Comparisons were mad e between the diffusion parameters of host cortex and corpus callosum, feta l cortical or tectal tissue transplanted to host midbrain ("C- and T-grafts ") and fetal cortical tissue transplanted to host cortex ("cortex-to-cortex " or C-C-grafts). In host cortex, alpha ranged from 0.20 +/- 0.01 (layer V) to 0.21 +/- 0.01 (layers III, IV and VI) and lambda from 1.59 +/- 0.03 (la yer VI) to 1.64 +/- 0.02 (layer III) (mean +/- S.E.M., n = 15), Much higher values were found in "young" C-grafts (81-150 days post-transplantation), where alpha = 0.34 +/- 0.01 and lambda = 1.78 +/- 0.03 (n = 13, as well as in T-grafts, where alpha = 0.29 +/- 0.02 and lambda = 1.85 +/- 0.04 (n = 7) . Further analysis revealed that diffusion in grafts was anisotropic and mo re hindered than in host cortex. The heterogeneity of diffusion parameters correlated with the structural heterogeneity of the neuropil, with the high est values of alpha in gray matter and the highest values of lambda in whit e matter bundles. Compared to "young" C-grafts, in "old" C-grafts tone year post-transplantation) both alpha and lambda were significantly lower, and there was a clear decrease in glial fibrillary acidic protein immunoreactiv ity throughout the grafted tissue. In C-C-grafts, alpha and lambda varied w ith the degree of graft incorporation into host tissue, but on average they were significantly lower (alpha = 0.24 +/- 0.01 and lambda = 1.66 +/- 0.02 , n = 8) than in young C- and T-grafts. Well-incorporated grafts revealed l ess astrogliosis, and alpha and lambda values were not significantly higher than those in normal host cortex. The observed changes in extracellular space diffusion parameters could affe ct the movement and accumulation of neuroactive substances and thus impact upon neuron-glia communication, synaptic and extrasynaptic transmission in the grafts. The potential relevance of these observations to human neuropat hological conditions associated with acute or chronic astrogliosis is consi dered. (C) 1999 IBRO. Published by Elsevier Science Ltd.