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| Model | Procedure model | Observations | References |
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| Electrical implants in male Sprague-Dawley rats (300–500 g) | Insulated stainless steel electrodes were implanted in the left dentate gyrus and angular bundle.
During the experiments, video-EEG was continuously recorded (24 h/day) until the animals were sacrificed.
Plasma was used by biochemical determinations. | The glutathione PEGylated (GSH-PEG) liposomal methylprednisolone (MP) treatment did not have any effect on SE duration and subsequent seizure development. Both the GSH-PEG liposomal MP-treated and vehicle-treated rats developed spontaneous seizures, indicating that GSH-PEG liposomal MP could not prevent epileptogenesis. | [108] |
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Hippocampal glutamine
synthetase deficiency by continuous microinfusion of methionine sulfoximine (MSO) in male Sprague-Dawley rats (180–220 g) | An osmotic pump was introduced through a burr hole in the skull and then into the right hippocampus. The pumps were filled with MSO to achieve the following drug delivery rates: 2.5, 1.25, and 0.625 µg/h for approximately 28 days. Separate pumps were filled with saline (0.9% NaCl) as a control.
For the GSH determination, the hippocampi were isolated.
GSH was measured using the spectrophotometric method with 5-thio-2-nitrobenzoic acid in a reaction coupled with GR. | Recurrent behavioral seizures occurred with all doses of MSO.
The intrahippocampal infusion of MSO was associated with a dose-dependent loss of neurons in the hippocampal formation and nearby brain areas.
No decrease in hippocampal GSH was observed in the lower-dosed animals (0.625 µg/h), whereas a 21% decrease was observed in the higher-dosed animals (2.5 µg/h) 10 days after the onset of MSO infusion. | [109] |
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| Lithium-pilocarpine in male Sprague-Dawley rats (260–300 g) | Lithium chloride (LiCl) (127 mg/kg) was injected intraperitoneally (i.p.) into both the experimental and control groups. Status epilepticus (SE) was induced by a subcutaneous injection of pilocarpine hydrochloride (25 mg/kg) 20 h after the LiCl treatment. For the GSH determination, the hippocampus, dentate gyrus, amygdala, entorhinal, piriform cortices (hippocampal formation), cerebral cortex, and cerebellum were removed and evaluated by high-performance liquid chromatography (HPLC). | The concentration of GSH was decreased in the hippocampal formation (22.6%) and cerebellum (6%) in the epileptic rats. | [110] |
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| Pilocarpine in 7- to 8-week-old male CD1 mice (25–40 g) | A single dose of pilocarpine was administered (330–345 mg/kg subcutaneously). All determinations with pilocarpine and controls were realized within 3.5–4 weeks after treatment, and the cerebral cortices, HF, and blood samples were obtained.
The GSH levels were measured by HPLC. | The level of GSH was significantly decreased (18%) in the hippocampal formation, whereas it was not significantly altered in the cortex in the pilocarpine mice. | [111] |
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| Pilocarpine in 2-month-old male Wistar rats (250–280 g) | The control animals received 0.9% i.p. saline, and in the experimental group, the animals were treated with a dose of pilocarpine hydrochloride (400 mg/kg, i.p.).
To determine the lipid peroxidation level, nitrite content, GSH concentration, and SOD and CAT activities, the rats (pilocarpine and control groups) were sacrificed 24 h after the treatment, and the brains were dissected on ice to remove the frontal cortex and striatum. | After pilocarpine-induced SE, significant increases (i.e., 47 and 59%) in the thiobarbituric acid reactive substance (TBARS) levels in the striatum and frontal cortex were observed. Marked increases were presented in nitrite content: 49 and 73% in the striatum and frontal cortex, respectively; the GSH concentrations decreased by 54 and 58% in the striatum and frontal cortex, respectively; the SOD in frontal cortex was verified by its increase of 24% after the seizures; and CAT increases of 39 and 49% were observed in the striatum and frontal cortex, respectively. | [112] |
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| Pilocarpine-lithium in 80- to 90-day-old male and female Wistar rats | SE was induced by administering pilocarpine hydrochloride (30 mg/kg i.p.) 22 h after LiCl (127 mg/kg i.p.). SE was interrupted after 2 h, and the rats were sacrificed 24 h later. The piriform and entorhinal cortices, temporal neocortex, thalamus, and hippocampus were dissected. Neurochemical determinations were performed using spectrophotometric methods: lipid peroxidation was analyzed by measuring the TBARS levels; SOD activity was analyzed with the xanthine-xanthine oxidase system, and GPx was analyzed by reducing the cumene hydroperoxide using GSH as a reducing agent. | The TBARS levels in all of the examined structures were significantly higher in the rats with SE: approximately 41% higher in the piriform and entorhinal cortices; 22% higher in the temporal neocortex; 25.7% higher in the thalamus and 15% higher in the hippocampus. SOD activities were significantly higher in the rats with SE in the piriform and entorhinal cortices (11.7%) and temporal neocortex (19.7%).
The GPx activities were significantly higher in the animals with SE in the piriform and entorhinal cortices (22.1%) and thalamus (8.9%). The authors did not observe significant sex-treatment interactions in the results in any of the investigated brain regions. | [113] |
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| Pilocarpine in male Wistar rats (250–350 g) | The experimental group was injected with pilocarpine (350 mg/kg i.p.), and the control rats were injected with a physiological salt solution. The rats were sacrificed by decapitation 2 h after drug administration, and the cortical regions were removed.
Neurochemical determinations were performed by spectrophotometric methods: lipid peroxidation was analyzed by measuring the oxidative marker malondialdehyde (MDA); SOD activity was measured with the xanthine/xanthine oxidase system; GPx was measured with H2O2 as the substrate and GR and NADPH as the enzymatic and nonenzymatic indicators, respectively; CAT activity was measured by H2O2 decomposition and GR and NADPH as the enzymatic and nonenzymatic indicators, respectively. The mRNA expression of the antioxidant enzymes was determined by real-time RT-PCR. | Pilocarpine increased the MDA levels (64%). All enzymatic activities were measured, and CAT, GPx, and SOD significantly increased in response to pilocarpine (28%, 28%, and 21%, resp.).
The GPx gene expression significantly increased in the pilocarpine group (1.47-fold), and the Mn-SOD expression also significantly increased (1.33-fold). The CAT expression was unchanged. | [114] |
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| Kainite in male Sprague-Dawley rats (300–350 g) | The rats were subcutaneously administered saline or 11 mg/kg kainite. The rats were sacrificed after 1 min of carbon dioxide inhalation and then were immediately decapitated at 8 h, 24 h, 48 h, 1 week, 3 weeks, and 6 weeks after injection to determine the acute, latent, and chronic periods of epileptogenesis. The hippocampal tissue was prepared for biochemical analysis.
GSH and GSSG were determined by HPLC. | Whole hippocampal tissue GSH decreased during the acute, latent, and chronic stages of the experimental temporal lobe epilepsy (TLE).
Hippocampal tissue GSSG levels increased substantially at 48 h after kainate treatment. Acute GSSG was increased at the 8 and 24 h time points. During the latent period, GSSG was elevated from 1 to 6 weeks after the kainite treatment. The GSH/GSSG ratio was significantly decreased in the kainate treatment groups from 24 h through 6 weeks. | [115] |
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