Diffusion barriers evoked in the rat cortex by reactive astrogliosis

Changes in extracellular space (ECS) diffusion parameters in astrogliotic tissue around a unilateral cortical stab wound were determined from concentration-time profiles of tetramethylammonium (TMA(+)) using TMA(+)-selective microelectrodes. Three diffusion parameters-ECS volume fraction alpha (alpha = ECS volume/ total tissue volume), tortuosity lambda (lambda(2) = D/ADC; where D is the free and ADC is the apparent diffusion coefficient of TMA(+) in the brain), and nonspecific TMA(+)uptake k'-were determined at 3, 7, 21, and 35 days postwounding (dpw), in the hemispheres ipsilateral and contralateral to the lesion. Following diffusion experiments, tissue sections were immunostained for glial fibrillary acidic protein (GFAP) and chondroitin-sulphate proteoglycans (CSPG). In the area 300-1000 micron around the wound, alpha was increased at 3, 7, and 21 dpw by about 20% but returned to control values at 35 dpw; lambda was increased at all four intervals, reaching a maximum at 7 dpw. k' was lower than in the contralateral hemisphere at 7, 21, and 35 dpw. Measurements 1,500-2,000 micron from the wound revealed only an increase in lambda at 7 dpw. The time course of changes in ECS diffusion parameters closely correlated with increased staining for GFAP and CSPG. Our results show that astrogliosis significantly changes the diffusion properties of nervous tissue, making it less permissive. Both hypertrophied astrocytic processes and an enhanced formation of some extracellular matrix molecules could affect, through changes in the diffusion of molecules in the ECS, neuron-glia communication, "cross-talk" between synapses, extrasynaptic transmission, and regenerative processes.