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Fig. 6 | Molecular Neurodegeneration

Fig. 6

From: Spatiotemporal progression of ubiquitin-proteasome system inhibition after status epilepticus suggests protective adaptation against hippocampal injury

Fig. 6

Proteasome inhibition protects from seizure-induced cell death. a Graph showing decreased KA-induced cell death in hippocampal primary neurons when pre-treated with the specific proteasome inhibitor epoxomicin (mean ± sem, *p <0.05, **p <0.01 and ***p <0.001 by one-way ANOVA with Fisher’s post hoc test; n = 3 per group). b. Decreased KA-induced cell death in hippocampal primary neurons when pre-treated with the specific proteasome inhibitor MG132 (mean ± sem, *p <0.05 by one-way ANOVA with Fisher’s post hoc test; n = 4 per group). c. Epoxomicin pre-treatment protects against cell death caused by increased extracellular [K+] (25 mM) in primary hippocampal cultures (mean ± sem, *p <0.05 by one way ANOVA with Fisher’s post hoc test; n = 3 per group). d. Graph and representative images of the CA3 region of the ipsilateral hippocampus showing decreased seizure-induced cell death in mice pretreated with epoxomicin. Status epilepticus was induced by an intra-amygdala injection of 0.3 μg KA and neuronal cell death was assessed 24 h later by counting FjB-positive cells in the ipsilateral hippocampal subfield CA3 (mean ± sem, *p <0.05 by one-way ANOVA with Fisher’s post hoc test; n = 11 (Control), 5 (30 and 300 μM epoxomicin) and 7 (100 μM epoxomicin). Scale bar, 50 μm. e. Pre-treatment with epoxomicin protects against seizure-induced cell death in a model of predominant necrotic cell death. Here, status epilepticus was induced by an intra-amygdala injection of 1.0 μg KA and neurodegeneration analyzed by counting FjB-positive cells in the hippocampal subfield CA3 24 h post-KA injection (mean ± sem, *p <0.05 by student’s two-tailed t-test; n = 4 (Control) and 5 (100 μM epoxomicin). f. Similar amount of high amplitude and high frequency polyspiking in mice subjected to status epilepticus during a recording period of 40 min pre-treated with different concentrations of epoxomicin (analysis started at time-point of intra-amygdala KA (0.3 μg) injection until lorazepam administration) (mean ± sem, *p <0.05 by ANOVA with Fisher’s post hoc test; n = 8 (Control), 5 (30 μM), 7 (100 μM) and 6 (300 μM)). g. Representative electroencephalogram (EEG) traces during status epilepticus from mice treated with vehicle or 100 μM epoxomicin showing similar high frequency and high amplitude polyspiking. h. Graph showing no significant differences in clinical seizures during the time of intra-amygdala KA (0.3 μg) injection until lorazepam administration between mice pre-treated with vehicle or 100 μM epoxomicin (mean ± sem, by two-way ANOVA with Bonferroni post hoc test; n = 5 per group)

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