Kindling and status epilepticus models of epilepsy: rewiring the brain

Morimoto, Kiyoshi; Fahnestock, Margaret; Racine, R.

doi:10.1016/j.pneurobio.2004.03.009

Cited by 740 publications

(586 citation statements)

References 615 publications

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“…SE triggers a well-characterized set of histopathological alterations in the hippocampus, including the rapid loss of pyramidal cells and hilar interneurons, reactive gliosis, and later, the sprouting of mossy fibers (Morimoto et al, 2004;Parent and Lowenstein, 2002). Along these lines, we previously reported that in mice, extensive cell loss in the hilar region was detected 6-h post-SE, and by 48-h post-SE, marked cell death in area CA1 and CA3, and microgliosis was observed throughout the hippocampus Lee et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

IGF‐1 receptor‐mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus

Choi

Cho

Hoyt

et al. 2008

Glia

127

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Adult progenitor cell proliferation in the subgranular zone (SGZ) of the dentate gyrus is a dynamic process that is modulated by an array of physiological process, including locomotor activity and novel environmental stimuli. In addition, pathophysiological events, such as ischemia and status epilepticus (SE), have been shown to stimulate neurogenesis. Currently, limited information is available regarding the extracellular stimuli, receptors, and downstream intracellular effectors that couple excitotoxic stimulation to progenitor cell proliferation. Here we show that pilocarpineinduced SE triggers a set of signaling events that impinge upon the p42/44 mitogen-activated protein kinase (MAPK) pathway to drive progenitor cell proliferation in the SGZ at 2-days post-SE. Increased proliferation was dependent on insulin-like growth factor-1 (IGF-1), which was localized to activated microglia near the SGZ. Using a combination of techniques, we show that IGF-1 is a CREB-regulated gene and that SE triggered CRE-dependent transcription in microglia at 2-days post-SE. Together, these data identify a potential signaling program that couples SE to progenitor cell proliferation. SE triggers CREB-dependent transcription in reactive microglia. As a CREB-target gene, IGF-1 expression is upregulated, and by 2-days post-SE, IGF-1 triggers MAPK pathway activation in progenitor cells and, in turn, an increase in progenitor cell proliferation.

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Section: Discussionmentioning

confidence: 99%

IGF‐1 receptor‐mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus

Choi

Cho

Hoyt

et al. 2008

Glia

127

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“…Of great interest in epileptic research is the temporal sequence of ictal discharge propagation during epileptic seizures (Faingold 2004;Morimoto et al, 2004;Blumenfeld 2005). 2-deoxyglucose uptake and Fos-like immunoreactivity have been employed to measure the activity of different structures related to seizure expressions.…”

Section: Discussionmentioning

confidence: 99%

Temporal sequence of ictal discharges propagation in the corticolimbic basal ganglia system during amygdala kindled seizures in freely moving rats

Shi

Luo

Woodward³

et al. 2007

Epilepsy Research

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We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures.

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“…We observed a significant two-to three-fold increase in p8GFAP in the cortex at 24h postinsult and a three-to seven-fold increase in p8GFAP and p13GFAP in various brain regions at 72h post-insult compared to controls. To further elucidate the role of seizures in GFAP phosphorylation, pGFAP expression could be examined without HI insult by using a standard kindling model or a status epilepticus model where spontaneous seizures are induced in rodents by electrical stimulation or chemical agents such as kainate or pilocarpine (for review, see [46]). …”

Section: Pgfap Expression In the Hi Brainmentioning

confidence: 99%

Phosphorylation of GFAP is Associated with Injury in the Neonatal Pig Hypoxic-Ischemic Brain

Sullivan

Miller

et al. 2012

Neurochem Res

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Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed in the astrocytecytoskeleton that plays an important role in the structure and function of the cell. GFAP can be phosphorylated at six serine (Ser) or threonine (Thr) residues but little is known about the role of GFAP phosphorylation in physiological and pathophysiological states. We have generated antibodies against two phosphorylated GFAP (pGFAP) proteins: p8GFAP, where GFAP is phosphorylated at Ser-8 and p13GFAP, where GFAP is phosphorylated at Ser-13. We examined p8GFAP and p13GFAP expression in the control neonatal pig brain and at 24h and 72h after an hypoxic-ischemic (HI) insult. Immunohistochemistry demonstrated pGFAP expression in astrocytes with an atypical cytoskeletal morphology, even in control brains. Semi-quantitative western blotting revealed that p8GFAP expression was significantly increased at 24h post-insult in HI animals with seizures in frontal, parietal, temporal and occipital cortices. At 72h post-insult, p8GFAP and p13GFAP expression were significantly increased in HI animals with seizures in brain regions that are vulnerable to cellular damage (cortex and basal ganglia), but no changes were observed in brain regions that are relatively spared following an HI insult (brain stem and cerebellum). Increased pGFAP expression was associated with poor neurological outcomes such as abnormal encephalography (EEG) and neurobehaviour, and increased histological brain damage.Phosphorylation of GFAP may play an important role in astrocyte remodelling during development and disease and could potentially contribute to the plasticity of the central nervous system. 3

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Kindling and status epilepticus models of epilepsy: rewiring the brain

Cited by 740 publications

References 615 publications

IGF‐1 receptor‐mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus

IGF‐1 receptor‐mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus

Temporal sequence of ictal discharges propagation in the corticolimbic basal ganglia system during amygdala kindled seizures in freely moving rats

Phosphorylation of GFAP is Associated with Injury in the Neonatal Pig Hypoxic-Ischemic Brain

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