Tel: +61 (0)7 3366 0363 Fax: +61 (0)7 3346 0330 The total number of words of the manuscript, including entire text from title page to figure legends: 8970 The number of words of the abstract: 192 The number of figures: 9 The number of tables: 2 1 Abstract The complex pathogenesis of temporal lobe epilepsy (TLE) includes neuronal and glial pathology, synaptic reorganization and an immune response. However, the spatio-temporal pattern of structural changes in the brain that provide a substrate

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... seizure generation and modulate the seizure phenotype is yet to be completely elucidated. We used quantitative MRI to study structural changes triggered by status epilepticus (SE) and their association with epileptogenesis and with activation of complement component 3 (C3). SE was induced by injection of pilocarpine in CD1 mice. Quantitative diffusion-weighted imaging and T2 relaxometry was performed using a 16.4 Tesla MRI scanner at 3 hours and 1, 2, 7, 14, 28, 35 and 49 days post-SE. Following longitudinal MRI examinations, spontaneous recurrent seizures and interictal spikes were quantified using continuous video-EEG monitoring. Immunohistochemical analysis of C3 expression was performed at 48 hours, 7 days and 4 months post-SE. Animals which developed spontaneous recurrent seizures following SE had specific transient and long-term structural changes within the hippocampus, amygdala, parahippocampal and piriform cortex that were not observed in nonepileptic mice. Chronic C3 upregulation was found in the hippocampus of epileptic animals within the areas of the persistent MRI changes.