Long-term consequences of a prolonged febrile seizure in a dual pathology model

Gibbs, Steve A.; Chattopadhyaya, Bidisha; Desgent, Sébastien; Awad, Patricia N.; Clerk-Lamalice, Olivier; Lévesque, Maxime; Vianna, Rose Mari Jacobsen; Rébillard, Rose-Marie; Delsemme, Andrée-Anne; Hébert, David; Tremblay, Luc; Lepage, Martin; Descarries, Laurent; Cristo, Graziella Di; Carmant, Lionel

doi:10.1016/j.nbd.2011.02.013

Cited by 27 publications

(34 citation statements)

References 61 publications

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“…Most studies, however, suggested that neuronal cell death was temporally related to the acute phase following SE (Gorter et al, 2003;Pitkänen et al, 2002). In addition, some studies demonstrated that neuronal cell death, particularly in hippocampus, preceded the occurrence of chronic recurrent seizures (Gibbs et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Continuous neurodegeneration and death pathway activation in neurons and glia in an experimental model of severe chronic epilepsy

Nobili

Colciaghi

Finardi

et al. 2015

Neurobiology of Disease

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Section: Discussionmentioning

confidence: 99%

Continuous neurodegeneration and death pathway activation in neurons and glia in an experimental model of severe chronic epilepsy

Nobili

Colciaghi

Finardi

et al. 2015

Neurobiology of Disease

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“…It is well-established that the induction of SE can readily damage the brain [5], [43]. However, previous papers failed to demonstrate epilepsy-related damage progression [5] or showed that SE-related damage preceded epilepsy onset [22]. A recent paper demonstrating progressive brain damage did not find a clear correlation with seizure activity [44].…”

Section: Discussionmentioning

confidence: 99%

“…Experimental models of cortical dysplasia might be instrumental in exploring mechanisms of epileptogenesis on one side and the possible progression of epilepsy related brain abnormalities on the other [22]–[25]. We recently demonstrated that in a rat model of acquired FCD (MAM/pilocarpine rats) [26] the occurrence of status epilepticus (SE) and spontaneous seizures gives rise to abnormally large cortical pyramidal neurons with neurofilament over-expression and recruitment of NMDA regulatory subunits at the post-synaptic membrane, strictly similar to the hypertrophic/dysmorphic neurons observed in human FCD [10].…”

Section: Introductionmentioning

confidence: 99%

Progressive Brain Damage, Synaptic Reorganization and NMDA Activation in a Model of Epileptogenic Cortical Dysplasia

Colciaghi¹,

Finardi²,

Nobili³

et al. 2014

PLoS ONE

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Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

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“…There is also indication for hippocampal hypoplasia as shown in postmortem analysis of human fetuses with doublecortin deficiency (33). In addition, in animal models of focal cortical malformations using freeze lesions acute changes in CA1 inhibitory network (34) have been followed by atrophy in the chronic phase (35). Nevertheless, the fact that the hippocampus is not the primary epileptogenic tissue in MCD may explain the lesser extent and degree of atrophy in these patients as compared to those with TLE.…”

Section: Discussionmentioning

confidence: 99%

Disentangling Hippocampal Shape Anomalies in Epilepsy

Kim¹,

Mansi²,

Bernasconi³

2013

Front. Neurol.

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Drug-resistant temporal lobe epilepsy (TLE) and epileptic syndromes related to malformations of cortical development (MCD) are associated with complex hippocampal morphology. The contribution of volume and position to the overall hippocampal shape in these conditions has not been studied. We propose a surface-based framework to localize volume changes through measurement of Jacobian determinants, and quantify fine-scale position and curvature through a medial axis model. We applied our methodology to T1-weighted 3D volumetric MRI of 88 patients with TLE and 78 patients with MCD, including focal cortical dysplasia (FCD, n = 29), heterotopia (HET, n = 40), and polymicrogyria (PMG, n = 19). Patients were compared to 46 age- and sex-matched healthy controls. Surface-based analysis of volume in TLE revealed severe ipsilateral atrophy mainly along the rostro-caudal extent of the hippocampal CA1 subfield. In MCD, patterns of volume changes included bilateral CA1 atrophy in HET and FCD, and left dentate hypertrophy in all three groups. The analysis of curvature revealed medial bending of the posterior hippocampus in TLE, whereas in MCD there was a supero-medial shift of the hippocampal body. Albeit hippocampal shape anomalies in TLE and MCD result from a combination of volume and positional changes, their nature and distribution suggest different pathogenic mechanisms.

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Long-term consequences of a prolonged febrile seizure in a dual pathology model

Cited by 27 publications

References 61 publications

Continuous neurodegeneration and death pathway activation in neurons and glia in an experimental model of severe chronic epilepsy

Continuous neurodegeneration and death pathway activation in neurons and glia in an experimental model of severe chronic epilepsy

Progressive Brain Damage, Synaptic Reorganization and NMDA Activation in a Model of Epileptogenic Cortical Dysplasia

Disentangling Hippocampal Shape Anomalies in Epilepsy

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