Glial activation in a pilocarpine rat model for epileptogenesis: a morphometric and quantitative analysis

Abstract

In this work we examined the correlation between long-term glial resilience and slow epileptogenesis using the pilocarpine-insult rat model. We assessed, quantitatively and morphometrically, glial fibrillary acidic protein (GFAP) expression and cell densities in hippocampus in a dose-response manner 2, 4 and 8 weeks after the pilocarpine insult. GFAP changes were correlated with observations on microglial activation. We used a commonly applied epileptogenic pilocarpine dose (380mg/kg) and its fractions of 1/10, 1/4 and 1/2. GFAP expression evaluated at 2 weeks revealed dose-dependent cytoskeletal hypertrophy and loss of GFAP+ cell densities in hippocampus. At 4-week timepoint, recoveries of the above mentioned parameters were observed in all groups, except for the full dose group in which the astrocytic hypertrophy reached the highest level, while its density dropped to the lowest level. Strong and localized microgliosis revealed by CD11b immunoreactivity was observed in hilus in the full dose group at 2- and 4-, persisting at 8-week timepoints. Through changing pattern analysis, we conclude that the loss of astroglial resilience is likely to be a determining factor for spontaneous recurrent seizure onset.