One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death

Chen, Linglin; Feng, Hang-Feng; Mao, Xue-Xia; Ye, Qing; Zeng, Ling‐Hui

doi:10.1007/s12264-013-1310-6

Cited by 20 publications

(8 citation statements)

References 34 publications

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“…In man, mortality is high during refractory SE that requires general anesthesia (32,33), and the 30-day mortality is ~35% in adults who experience at least an hour of SE (34). Mortality is also encountered in rodents experiencing SE, and mortality rate is positively correlated with time spent in SE (35). We found no role for myeloid cell EP2 or neuronal EP2 in acute mortality during SE.…”

Section: Se Results In the Rapid Induction Of Numerous Inflammatory Cmentioning

confidence: 67%

Opposing effects of prostaglandin receptor EP2 signaling in mouse immune cells and neurons after status epilepticus

Varvel

Chen

Biegel

et al. 2018

Preprint

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Seizures reduce quality of life, promote the development of epilepsy, and can be fatal.We previously identified inflammation, via prostaglandin receptor EP2 activation, as a driver of undesirable seizure-induced effects. However, the relevant EP2-expressing cell types remain unclear. We identify innate immune cells as a driver of the EP2-related negative consequences of seizures, whereas neuronal EP2 signaling is protective. Genetic removal of EP2 from immune cells was beneficial, accelerating weight gain and limiting behavioral deficits.Elimination of EP2 from neurons was harmful, worsening behavioral deficits and promoting neuronal damage. These findings enhance our understanding of the complex inflammatory processes engaged after seizures and will assist in the development of beneficial therapies to enhance quality of life in individuals susceptible to seizures.

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Section: Se Results In the Rapid Induction Of Numerous Inflammatory Cmentioning

confidence: 67%

Opposing effects of prostaglandin receptor EP2 signaling in mouse immune cells and neurons after status epilepticus

Varvel

Chen

Biegel

et al. 2018

Preprint

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“…All behavioral experiments were conducted the next day after 4 weeks of daily rapamycin treatment. Morris water maze was conducted as described previously [ 13 ]. Briefly, a platform of 10 cm in diameter was submerged 1 cm beneath the surface and located at a fixed position and remained constant throughout the training period.…”

Section: Methodsmentioning

confidence: 99%

Effect of Chronic Administration of Low Dose Rapamycin on Development and Immunity in Young Rats

Liu

Chen

et al. 2015

PLoS ONE

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Mammalian target of rapamycin (mTOR) regulates cell growth, cell differentiation and protein synthesis. Rapamycin, an inhibitor of mTOR, has been widely used as an immunosuppressant and anti-cancer drug. Recently, mTOR inhibitors have also been reported to be a potential anti-epileptic drug, which may be effective when used in young patients with genetic epilepsy. Thus, a suitable dose of rapamycin which can maintain the normal function of mTOR and has fewer side effects ideally should be identified. In the present study, we first detected changes in marker proteins of mTOR signaling pathway during development. Then we determined the dose of rapamycin by treating rats of 2 weeks of age with different doses of rapamycin for 3 days and detected its effect on mTOR pathway. Young rats were then treated with a suitable dose of rapamycin for 4 weeks and the effect of rapamycin on mTOR, development and immunity were investigated. We found that the expression of the marker proteins of mTOR pathway was changed during development in brain hippocampus and neocortex. After 3 days of treanent, 0.03 mg/kg rapamycin had no effect on phospho-S6, whereas 0.1, 0.3, 1.0 and 3.0 mg/kg rapamycin inhibited phospho-S6 in a dose-dependent manner. However, only 1.0 mg/kg and 3.0 mg/kg rapamycin inhibited phospho-S6 after 4 weeks treatment of rapamycin. Parallel to this result, rats treated with 0.1 and 0.3 mg/kg rapamycin had no obvious adverse effects, whereas rats treated with 1.0 and 3.0 mg/kg rapamycin showed significant decreases in body, spleen and thymus weight. Additionally, rats treated with 1.0 and 3.0 mg/kg rapamycin exhibited cognitive impairment and anxiety as evident by maze and open field experiments. Furthermore, the content of IL-1β, IL-2, IFN-γ, TNF-α in serum and cerebral cortex were significantly decreased in 1.0 and 3.0 mg/kg rapamycin-treated rats. The expression of DCX was also significantly decreased in 1.0 and 3.0 mg/kg rapamycin-treated rats. However, rats treated with 1.0 mg/ kg rapamycin exhibited fewer and milder side effects than those treated with 3.0 mg/kg. In summary, all these data suggest that there is not a rapamycin dose that can inhibit mTOR for epilepsy without causing any side effects, but 1 mg /kg may be the optimal dose for young rats for suppressing mTOR with relatively few side effects.

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“…Lithium was intraperitoneally injected to rats (100 mg/ml), and pilocarpine was intraperitoneally injected (10 mg/ml) after 18-20 h [3]. Epilepsy intensity scoring was performed according to Racine graded standard [23].…”

Section: Induced Epilepsymentioning

confidence: 99%

“…Preclinical studies demonstrated that accumbens nucleus shell (ACbSh) had been involved in the progress of epilepsy. Pilocarpine-induced rat epilepsy models showed that hippocampus had severe degeneration of neurons, while multiple nucleus in thalamus and ACbSh had also suffered from neuronal degeneration [3,23]. However, details were not clear as to the association between ACbSh and epilepsy.…”

Section: Introductionmentioning

confidence: 99%

Effect of accumbens nucleus shell lesioning on bitemporal lobe epilepsy in rat model

Fu¹,

Liu²,

Yang³

et al. 2018

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Introduction: To explore the effect of accumbens nucleus shell (ACbSh) lesioning on bitemporal lobe epilepsy. Material and methods: Adult Wistar rats (male) were enrolled and randomly assigned into the control group and epilepsy groups with multiple time-points. Lithium-pilocarpine was used to establish the rat epilepsy model, while the control group received an equal amount of saline. Ibotenic acid stereotaxic injection was performed to cause accumbens nucleus shell lesioning for specific groups. Cascade software was used for electroencephalogram (EEG) examination. Fluoro-Jade C staining was performed to examine neuronal degeneration. Results: Latency period of the epilepsy in epilepsy groups was 15.3 ± 1.1 min, and epilepsy intensity was 4.8 ± 0.5 events/ 12 h. ACbSh lesioning significantly reduced aggressive behavior. Compared with epilepsy groups without ACbSh lesioning, ACbSh lesioning significantly decreased epileptic seizures and reduced epileptic duration (p < 0.05). EEG showed that there were still sharp waves in the hippocampus and amygdala region after ACbSh lesioning, but epileptic discharge in prefrontal cortex was significantly decreased (p < 0.05), while epilepsy groups without ACbSh lesioning had more sharp waves in the prefrontal cortex, hippocampus and amygdala region. Fluoro-Jade C staining showed that ACbSh lesioning significantly decreased grades of neuronal degeneration (p < 0.05). Conclusions: Recurrent epilepsy caused neuronal degeneration via ACbSh region-related pathways, and ACbSh lesioning could mitigate epilepsy-caused neuronal degeneration by reducing epileptic discharge.

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One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death

Cited by 20 publications

References 34 publications

Opposing effects of prostaglandin receptor EP2 signaling in mouse immune cells and neurons after status epilepticus

Opposing effects of prostaglandin receptor EP2 signaling in mouse immune cells and neurons after status epilepticus

Effect of Chronic Administration of Low Dose Rapamycin on Development and Immunity in Young Rats

Effect of accumbens nucleus shell lesioning on bitemporal lobe epilepsy in rat model

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