Structural and functional changes during epileptogenesis in the mouse model of medial temporal lobe epilepsy

Abstract

An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy. The results indicate that high-field (4.7T) MRI parameters (T2-weighted; T2-quantitative) allow to detect the gradual neuro-anatomical changes that occur during epileptogenesis while electrophysiological parameters (number and duration of Hippocampal Paroxysmal Discharges) allow to assess the dysfunctional changes through the quantification of epileptiform activity. We found a strong correlation between EEG-based markers (invasive recording) and MRI-based parameters (non-invasive) periodically computed over the `latent period' that spans over two weeks, on average. These results indicated that both structural and functional changes occur in the considered epilepsy model and are considered as biomarkers of the installation of epilepsy. Additionally, such structural and functional changes can also be observed in human temporal lobe epilepsy. Interestingly, MRI imaging parameters could be used to track early (day-7) structural changes (gliosis, cell loss) in the lesioned brain and to quantify the evolution of epileptogenesis after traumatic brain injury.

Neuroimaging in animal models of epilepsy

“…In addition, T2 relaxation time in the amygdala in rats 30 days following pilocarpine-induced SE correlated with hyperactivity behavior during open field test (Suleymanova et al, 2016). Finally, Dietrich and colleagues reported correlations between T2 relaxation time with the number and duration of hippocampal paroxysmal discharges measured during epileptogenesis in the intrahippocampal KA mouse model of epilepsy (Dietrich et al, 2016).…”

A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy

“…Magnetic resonance imaging (MRI) is able to reliably detect regional structural changes of the epileptic brain in relation to epileptogenesis of animal models ( 13 , 14 ). Hippocampal atrophy is the most featured structural alternation of the pilocarpine-SE model of spontaneous chronic temporal epilepsy ( 13 , 15 , 16 ).…”

A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures

“…The present study employed TSPO PET and T2w and diffusion MRI to longitudinally interrogate neuropathology and neuroinflammation following acute DFP intoxication up to approximately 6 months (168 days) post-exposure using a panel of quantitative imaging metrics. To date, the resulting data and analysis represent the most comprehensive in vivo imaging-based assessment of acute OP intoxication in any preclinical model ( Bar-Klein et al 2016 , 2017 ; Bhagat et al 2001 , 2005 ; Carpentier et al, 2008 ; Gullapalli et al, 2010 ; Hobson et al 2017a , 2017b , 2019 ; Reddy et al, 2020 ; Rosman et al, 2012 ; Shrot et al, 2012 ; Swissa et al, 2020 ; Testylier et al, 2007 ), and one of the largest in vivo imaging-based assessments in a preclinical seizure model ( Blumenfeld, 2007 ; Dietrich et al, 2016 ; Kharatishvili et al, 2014 ; Reddy et al, 2019 ; Roch et al, 2002 ; Salo et al, 2017 ; Tokumitsu et al, 1997 ; van Vliet et al, 2016 ). The results of this study demonstrate that a single exposure to DFP at a level that triggers acute SE results in profound and progressive brain atrophy and multiple distinct lesion types apparent on T2w and diffusion MR images that vary by brain region and time post-exposure.…”