In vivo models of cortical acquired epilepsy

Chauvette, Sylvain; Soltani, Sara; Seigneur, Josée; Timofeev, Igor

doi:10.1016/j.jneumeth.2015.08.030

Cited by 35 publications

(33 citation statements)

References 164 publications

(237 reference statements)

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“…These findings are consistent with observations in other models of PTE and indicative of cortical hyperexcitability and decreased seizure threshold in vivo [ 43 ]. Recently, spontaneous electrographic and behavioral seizures have also been demonstrated in a high percentage of undercut mice at old age by another group [ 29 ], which further confirm our observation in this study and support the use of the rodent model for epilepsy research.…”

Section: Discussionsupporting

confidence: 91%

“…In cortical slices prepared from undercut rats, spontaneous and evoked epileptiform discharges can be recorded in the majority of slices after 2 weeks following injury [ 13 ]. However, although anecdotal observations of electrographic and behavioral seizures were made in a few undercut rats, systematic characterization of chronic epileptic seizure of this model in rodents has not been completed [ 21 , 29 ]. The lack of this critical piece of information substantially undermines the validity of the model and limits its use in epilepsy research.…”

Section: Introductionmentioning

confidence: 99%

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Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice

Ping

Jin

2016

PLoS ONE

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Posttraumatic epilepsy (PTE) usually develops in a small percentage of patients of traumatic brain injury after a varying latent period. Modeling this chronic neurological condition in rodents is time consuming and inefficient, which constitutes a significant obstacle in studying its mechanism and discovering novel therapeutics for its prevention and treatment. Partially isolated neocortex, or undercut, is known to induce cortical hyperexcitability and epileptiform activity in vitro, and has been used extensively for studying the neurophysiological mechanism of posttraumatic epileptogenesis. However, whether the undercut lesion in rodents causes chronic epileptic seizures has not been systematically characterized. Here we used a miniature telemetry system to continuously monitor electroencephalography (EEG) in adult C57BL mice for up to 3 months after undercut surgery. We found that 50% of animals developed spontaneous seizures between 16–50 days after injury. The mean seizure duration was 8.9±3.6 seconds, and the average seizure frequency was 0.17±0.17 times per day. There was no progression in seizure frequency and duration over the recording period. Video monitoring revealed behavioral arrests and clonic limb movement during seizure attacks. A pentylenetetrazol (PTZ) test further showed increased seizure susceptibility in the undercut mice. We conclude that undercut lesion in mice is a model of chronic PTE that involves spontaneous epileptic seizures.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice

Ping

Jin

2016

PLoS ONE

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“…We analyzed FS interneurons of neocortical layer V in the UC model to determine whether there were abnormalities in their axons and presynaptic terminals that could result in defects in GABAergic transmission. Interictal discharges originate in layer V of the UC (Prince and Tseng, 1993); (Hoffman et al, 1994) and alterations in FS interneurons in this lamina could contribute to hyperexcitability and epileptiform bursts in in vitro cortical slices (Prince and Tseng, 1993; Hoffman et al, 1994) and seizures in vivo (Chauvette et al, 2016; Ping and Jin, 2016a). We identified FS cells in whole cell recordings from their electrophysiological phenotype (Xiang et al, 1998) and, retrospectively, appearance following biocytin labeling.…”

Section: Methodsmentioning

confidence: 99%

Structural alterations in fast-spiking GABAergic interneurons in a model of posttraumatic neocortical epileptogenesis

Parada

Shen

et al. 2017

Neurobiology of Disease

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Electrophysiological experiments in the partial cortical isolation (“undercut” or “UC”) model of injury-induced neocortical epileptogenesis have shown alterations in GABAergic synaptic transmission attributable to abnormalities in presynaptic terminals. To determine whether the decreased inhibition was associated with structural abnormalities in GABAergic interneurons, we used immunocytochemical techniques, confocal microscopy and EM in UC and control sensorimotor rat cortex to analyze structural alterations in fast-spiking parvalbumin-containing interneurons and pyramidal (Pyr) cells of layer V. Principle findings were: 1) There were no decreases in counts of parvalbumin (PV)- or GABA-immunoreactive interneurons in UC cortex, however there were significant reductions in expression of VGAT and GAD-65 and -67 in halos of GABAergic terminals around Pyr somata in layer V. 2) Consistent with previous results, somatic size and density of Pyr cells was decreased in infragranular layers of UC cortex. 3) Dendrites of biocytin-filled FS interneurons were significantly decreased in volume. 4) There were decreases in the size and VGAT content of GABAergic boutons in axons of biocytin-filled FS cells in the UC, together with a decrease in colocalization with postsynaptic gephyrin, suggesting a reduction in GABAergic synapses. Quantitative EM of layer V Pyr somata confirmed the reduction in inhibitory synapses. 5) There were marked and lasting reductions in brain derived neurotrophic factor (BDNF)-IR and -mRNA in Pyr cells and decreased TrkB-IR on PV cells in UC cortex. 6) Results lead to the hypothesis that reduction in trophic support by BDNF derived from Pyr cells may contribute to the regressive changes in axonal terminals and dendrites of FS cells in the UC cortex and decreased GABAergic inhibition.

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“…Furthermore, lateral FPI decreases the threshold for PTZ‐induced and spontaneous epileptic events in mice . It should, however, be pointed out that a plethora of cortical epileptogenesis trauma models exist that have distinct characteristics with respect to epileptogenicity (as excellently reviewed in ). Pathomechanistically, BBB dysfunction and selective inhibitory neurone degeneration point to transient and permanent structural and cellular consequences of traumatic episodes to human brain tissue that require systematic workup in rodent models .…”

Section: Lesion‐induced Epileptogenesis Modelsmentioning

confidence: 99%

Review: Animal models of acquired epilepsy: insights into mechanisms of human epileptogenesis

Becker

2018

Neuropathology Appl Neurobio

130

117

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A. J. Becker (2018) Neuropathology and Applied Neurobiology 44, 112-129 Animal models of acquired epilepsy: insights into mechanisms of human epileptogenesisIn many patients who suffer from epilepsies, recurrent epileptic seizures do not start at birth but develop later in life. This holds particularly true for epilepsies with a focal seizure origin including focal cortical dysplasias and temporal lobe epilepsy (TLE). TLE most frequently has its seizure onset in the hippocampal formation. Hippocampal biopsies of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure control most frequently reveal the damage pattern of hippocampal sclerosis, that is, segmental neuronal cell loss and concomitant astrogliosis. Many TLE patients report on transient brain insults early in life, which is followed by a 'latency' period lacking seizure activity of months or even years before chronic recurrent seizures start. The plethora of structural and cellular mechanisms that convert the hippocampal formation to become chronically hyperexcitable after a transient insult to the brain are summarized under the term epileptogenesis. In contrast to the obstacles arising for experimental studies of epileptogenesis aspects in human surgical hippocampal tissue, recent animal model approaches allow insights into mechanisms of epileptogenesis. Relevant models of transient brain insults in this context comprise several distinct types of lesions including excitoxic status epilepticus (SE), electrical seizure induction, traumatic brain injury, induction of inflammatory processes by hyperthermia and viral inflammation and others. In pathogenetic terms, aberrant transcriptional and epigenetic reprogramming, acquired channel-and synaptopathies, neuronal network and blood-brain barrier dysfunction as well as innate and adaptive immunitymediated damage play major roles. In subsequent steps, respective animal models have been used in order to test whether this dynamic process can be either retarded or even abolished by interfering with epileptogenic mechanisms. Well-controlled subsequent analyses of epileptogenic cascades characterized in animal models using carefully stratified human hippocampal biopsies to exploit the unique opportunities given by these rare and precious brain tissue samples aim to translate into novel antiepileptogenic approaches. Respective preclinical tests can open entirely new perspectives for tailor-made treatments in patients with the potential to avoid the emergence of chronic focal seizure events.

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In vivo models of cortical acquired epilepsy

Cited by 35 publications

References 164 publications

Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice

Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice

Structural alterations in fast-spiking GABAergic interneurons in a model of posttraumatic neocortical epileptogenesis

Review: Animal models of acquired epilepsy: insights into mechanisms of human epileptogenesis

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