Abstract

Objective To determine the intervention of mycophenolate mofetil(MMF) in glial scar formation and learning and memory function in a rat model of diffuse axonal injury(DAI). Methods Ninety-six SD rats were randomly divided into sham group, normal saline (NS) group and mycophenolate mofetil (MMF) group according to the random number table, with 32 rats per group. Immunohistochemistry was used to detect activated microglia cells, activated astrocytes and chondroitin sulphate proteoglycanns (CSPGs) in the hippocampus. Image-Pro Plus software was used to quantitatively assess the changes of activated microglia cells, activated astrocytes and CSPGs. Morris water maze was applied for testing rat learning and memory function. Integrated absorbance (IA) of major constituents (microglia, astrosyte, chondroitin sulphate proteoglycan) of the glial scar was determined and analyzed for the correlation with the parameters of MWM. Results At 7, 14 and 28 days after injury, MMF group showed decreased IA of activated microglia in the hippocampus compared to sham and NS groups (P<0. 05). At 7-11 days after injury, percent distance and percent time in the target quadrant of Morris water maze did not differ significantly among the three groups and were not related to the IA of glial scar. At 28-32 days after injury, percent distance and percent time in the target quadrant of Morris water maze lowered significantly in MMF group. At 28 days after injury, IA of the glial scar had a positive correlation with mean speed and mean escape latency, but negative correlation with percent distance and time in the target quadrant that measured in Morris water maze at 28-32 days after injury. Conclusion MMF significantly attenuates glial scar formation into the hippocampus and improves learning and memory function in rats during the recovery stage when administered in the early stage after DAI. Key words: Diffuse axonal injury; Hippocampus; Mycophenolate mofetil

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