Abstracts

Rationale: The neurobiological processes resulting in epilepsy, known as epileptogenesis, are incompletely understood. Manganese-enhanced MRI (MEMRI) provides superior structural resolution, particularly of the hippocampal subregions. This longitudinal study aims to characterise the pathological changes in the hippocampus of the post-kainic acid (KA) status epilepticus (SE) and the kindling rat model of temporal lobe epilepsy using MEMRI in vivo. Methods: Serial T1-weighted MEMRI acquisitions were performed in the KA model (n= 14), kindling model (n=14) and control rats (n=17) at three time points: baseline, early epileptogenesis and late epileptogenesis. MnCl2 was administered in the right lateral ventricle (10 µl 50 mM, KA model) or by iv infusion (8 ml/kg of 75 mM, kindling model) 1 day before each scan. Regions of interest were drawn around the whole brain, left hippocampus and several subregions of the hippocampus (CA1, CA3 and dentate gyrus). Brains were collected for histological analysis. Results: Low-seizing KA animals (cut-off <0.5 seizures/day detected by 24h video/EEG) showed a significant increase in MEMRI signal intensity in the dentate gyrus and CA3 (p<0.05), and a trend of increasing intensity in CA1 (p=0.08) when compared to controls and high-seizing animals After kindling, a significant increase in MEMRI signal intensity was found in the contralateral hippocampus (p<0.05), and a trend of increasing intensities were observed in subregions CA3 and CA1 (p=0.06) compared to controls. MEMRI signal intensity in several hippocampal subregions was inversely correlated with seizure frequency (KA model) and seizure class (kindling model) (p<0.05). CA1 thickness was significantly reduced at both early and late epileptogenesis time points in the KA model (p<0.05), while in the kindling model a trend for a reduction was only seen at the last time point (p=0.06). CA1 thickness was positively correlated with seizure frequency in the KA model (p<0.05). Significant cell loss, mossy fiber sprouting and synaptogenesis were found in the KA model. Cell numbers correlated with MEMRI signal intensity while no association was found between mossy fiber sprouting or synaptogenesis and MEMRI intensity.