title: MRI changes and complement activation correlate with epileptogenicity in a mouse model of temporal lobe epilepsy.
abstract: The complex pathogenesis of temporal lobe epilepsy 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 for seizure generation and modulate the seizure phenotype is yet to be completely elucidated. We used quantitative magnetic resonance imaging (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 h 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 h, 7 days, and 4 months post-SE. MRI changes were dynamic, reflecting different outcomes in relation to the development of epilepsy. Apparent diffusion coefficient changes in the hippocampus at 7 days post-SE correlated with the severity of the evolving epilepsy. C3 activation was found in all stages of epileptogenesis within the areas with significant MRI changes and correlated with the severity of epileptic condition.
authors.affiliation: Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, 4072, Australia, i.kharatishvili@uq.edu.au.
authors.forename: Irina
authors.initials: I
authors.lastname: Kharatishvili
authors.forename: Zuyao Y
authors.initials: ZY
authors.lastname: Shan
authors.forename: David T
authors.initials: DT
authors.lastname: She
authors.forename: Samuel
authors.initials: S
authors.lastname: Foong
authors.forename: Nyoman D
authors.initials: ND
authors.lastname: Kurniawan
authors.forename: David C
authors.initials: DC
authors.lastname: Reutens
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001931:Brain Mapping; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism*; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis* / Q000209:etiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D018721:Muscarinic Agonists / Q000633:toxicity; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D012598:Sclerosis / Q000209:etiology; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D003176:Complement C3; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D018721:Muscarinic Agonists; D010862:Pilocarpine; D010751:Phosphopyruvate Hydratase