Longitudinal changes in gray and white matter microstructure during epileptogenesis in pilocarpine-induced epileptic rats

Abstract

PurposeTemporal lobe epilepsy is associated with tissue abnormalities of several gray and white matter structures that are reproduced in animal models. Few longitudinal studies have focused on the identification of structural differences during epileptogenesis. The diffusion tensor model is a useful tool for evaluating cell death, gliosis, and axonal plasticity in epileptic subjects. This study aimed to evaluate temporal tissue changes after experimental status epilepticus in an animal model of chronic temporal lobe epilepsy. MethodsSystemic pilocarpine-induced status epilepticus in adult Sprague-Dawley rats. Animals were scanned using diffusion tensor imaging (DTI) at three time points: prior to status epilepticus, and 24 and 64 days post-induction (early and late chronic, respectively). Fractional anisotropy, apparent diffusion coefficient, axial diffusivity (D║), and radial diffusivity (D┴) were evaluated in white (fimbria, cingulum, corpus callosum, and internal capsule) and gray (dorsal hippocampus, dentate gyrus, and CA3) matter regions for the three time points. Histological assessment of neurodegeneration in Klüver-Barrera preparations from the same animals was performed. ResultsSignificantly reduced volume of dorsal hippocampus and fimbria of the epileptic animals was observed already at 24 days post-status epilepticus. Progressive changes of DTI parameters in both the white and gray matter structures of the experimental group were also observed. Stained sections confirmed such alterations. ConclusionOur study revealed time-dependent diffusion changes in gray and white matter structures after pilocarpine-induced status epilepticus. The characterization of these alterations over time may be potential imaging markers for epileptogenesis.