Abstracts

Rationale: There is evidence that the immature brain is more vulnerable to seizure induction, however the chronic effects of seizures during development, especially as they pertain to epileptogenesis, remain to be fully understood. Diffusion tensor imaging (DTI) has emerged as a potentially valuable investigative tool for characterizing the evolution and nature of microstructural abnormalities that accompany epileptogenesis. In this study, ex-vivo DTI was used in a rat model to compare the long-term effects of status epilepticus (SE) at different ages during development.Methods: Kainic acid was injected (i.p.) at age appropriate doses to induce SE in rats at post-natal day (P)15 (n=4), P25 (n=5), P35 (p=4) and P70 (n=2). Brains were harvested from these rats at P270 as well as from control rats (n=3). Ex-vivo DTI was performed with the following parameters: TE/TR=22.94/2000ms, FOV=30x30mm, matrix=256x256, slices=35, thickness=0.5mm, 3 reference images and 30 diffusion weighted images with b=~1200s/mm2 in non-colinear directions. Region of interest analysis was performed to determine DTI values of fractional anisotropy (FA), mean diffusion (MD), axial and radial diffusivity (DA and DR) for the corpus callosum (CC), fornix and hippocampal subregions including orientation quantified by mean direction unit vector (MDUV) analysis. Orientation vectors falling outside the 95% confidence angle for the control group were considered to be significantly different from control.Results: For rats with SE at P15, CC FA and DA were significantly reduced (p=0.007 and p=0.008), FA was decreased in the dorsal dentate gyrus (p=0.041) and 3/4 sample MDUVs fell outside of the normal range, toward the A-P axis. For rats with SE at P25, there were no DTI index abnormalities, however 3/5 sample MDUVs fell outside of the normal range (1 toward A-P axis, 3 toward D-V axis). For rats with SE at P35 and P70, fornix FA was significantly reduced (p=0.012 and 0.047) and fornix DR was significantly increased (p= 0.011 and 0.041), FA was increased in the dorsal hippocampus (p= 0.067 and 0.063) and all sample MDUVs fell outside of the normal range toward the D-V axis.Conclusions: Distinct age-dependent patterns of long-term DTI abnormalities were detected with differences most evident between rats with SE at P15 and those with SE at P35 or P70. The reported abnormalities suggest different mechanisms of white matter damage and opposite hippocampal FA and orientation changes between these groups. Rats with SE at P25 were a distinct group with lack of white matter damage and heterogeneous hilar orientation patterns. The novel implementation of MDUV analysis for DTI data provided unique insight into the microstructural abnormalities following SE and this approach may be useful for future DTI studies of hippocampal plasticity and epileptogenesis. The results demonstrate that the long-term consequences of SE are age-specific, with distinctive structural outcomes detectable in adulthood as a function of developmental age.