Metyrapone prevents brain damage induced by status epilepticus in the rat lithium-pilocarpine model

Garcı́a-Garcı́a, Luis; Shiha, Ahmed Anis; Rosa, Rubén Fernández de la; Delgado, Mercedes; Silván, Ágata; Bascuñana, Pablo; Gómez, Francisca; Pozo, Miguel A.

doi:10.1016/j.neuropharm.2017.05.007

Cited by 23 publications

(45 citation statements)

References 63 publications

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“…Lithium chloride (Sigma, USA) and pilocarpine (Sigma, USA) were used to induce SE (García-García et al, 2017). Rats were intraperitoneally injected with 127 mg/kg lithium chloride in 0.9% saline 20–24 h before pilocarpine injection.…”

Section: Methodsmentioning

confidence: 99%

The Neuroprotective Effect of Astaxanthin on Pilocarpine-Induced Status Epilepticus in Rats

Deng

Wang

et al. 2019

Front. Cell. Neurosci.

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Cognitive dysfunction is one of the serious complications induced by status epilepticus (SE), which has a significant negative impact on patients’ quality of life. Previous studies demonstrated that the pathophysiological changes after SE such as oxidative stress, inflammatory reaction contribute to neuronal damage. A recent study indicated that preventive astaxanthin (AST) alleviated epilepsy-induced oxidative stress and neuronal apoptosis in the brain. In the present study, rats were treated with vehicle or AST 1 h after SE onset and were injected once every other day for 2 weeks (total of seven times). The results showed that the cognitive function in SE rats was significantly impaired, and AST treatment improved cognitive function in the Morris water maze (MWM). Magnetic resonance imaging (MRI), hematoxylin-eosin (HE) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining showed obvious damage in the hippocampus of SE rats, and AST alleviated the damage. Subsequently, we evaluated the effect of AST on relative pathophysiology to elucidate the possible mechanisms. To evaluate the oxidative stress, the expression of malondialdehyde (MDA) and superoxide dismutase (SOD) in plasma were detected using commercially available kits. NADPH oxidase-4 (Nox-4), p22phox, NF-E2-related factor 2 (Nrf-2), heme oxygenase 1 (Ho-1) and sod1 in the parahippocampal cortex and hippocampus were detected using western blot and real-time polymerase chain reaction (RT-PCR). The levels of MDA in plasma and Nox-4 and p22phox in the brain increased in SE rats, and the levels of SOD in plasma and Nrf-2, Ho-1 and sod1 in the brain decreased. Treatment with AST alleviated these changes. We also detected the levels of inflammatory mediators like cyclooxygenase-2 (cox-2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and NF-κB phosphorylation p65 (p-p65)/p65 in the brain. The inflammatory reaction was significantly activated in the brain of SE rats, and AST alleviated neuroinflammation. We detected the levels of p-Akt, Akt, B-cell lymphoma-2 (Bcl-2), Bax, cleaved caspase-3, and caspase-3 in the parahippocampal cortex and hippocampus using western blot. The levels of p-Akt/Akt and Bcl-2 decreased in SE rats, Bax and cleaved caspase-3/caspase-3 increased, while AST alleviated these changes. The present study indicated that AST exerted an reobvious neuroprotective effect in pilocarpine-induced SE rats.

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Section: Methodsmentioning

confidence: 99%

The Neuroprotective Effect of Astaxanthin on Pilocarpine-Induced Status Epilepticus in Rats

Deng

Wang

et al. 2019

Front. Cell. Neurosci.

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“…Digital images were obtained using an epifluorescence microscope (Nikon coupled to a high-level color camera Model SHC-410NAD). The CA1 area and the parietal neocortex were chosen based on morphological and pharmacological studies in pilocarpine-treated animals (Curia et al, 2008; Rossi et al, 2013; Arisi et al, 2015; García-García et al, 2017). In each section, photomicrographs of four fields within the parietal cortex (layers 2 and 3) and three fields of the CA1 hippocampal region (including Stratum Oriens, Stratum Pyramidalis, Stratum Radiatum, and Stratum Lacunosum Moleculare) were analyzed, using the ImageJ software (National Institutes of Health, United States, version 1.46r).…”

Section: Methodsmentioning

confidence: 99%

Taurine/Pilocarpine Interaction in the Malnourished Rat Brain: A Behavioral, Electrophysiological, and Immunohistochemical Analysis

et al. 2019

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This study aimed to evaluate the possible protective role of taurine on anxiety-like behavior, brain electrical activity and glial cell immunoreactivity in well-nourished and malnourished rats that were treated with a subconvulsing dose of pilocarpine. Newborn Wistar rats were subjected to normal or unfavorable lactation conditions, represented by the suckling of litters with 9 or 15 pups, resulting in well-nourished and malnourished animals, respectively. Each nutritional group was split into five subgroups that were treated from postnatal day (PND) 35 to 55 with 300 mg/kg/day of taurine + 45 mg/kg/day of pilocarpine (group T + P), taurine only (group T), pilocarpine only (group P), vehicle control (group V), or not treated control (group naïve; Nv). At PND56-58, the groups were subjected to the elevated plus-maze behavioral tests. Glycemia was measured on PND59. Between PND60 and PND65, the cortical spreading depression (CSD) was recorded in the cerebral cortex, and the levels of malondialdehyde and microglial and astrocyte immunoreactivity were evaluated in the cortex and hippocampus. Our data indicate that treatment with taurine and pilocarpine resulted in anxiolytic-like and anxiogenic behavior, respectively, and that nutritional deficiency modulated these effects. Both treatments decelerated CSD propagation and modulated GFAP- and Iba1-containing glial cells. Pilocarpine reduced body weight and glycemia, and administration of taurine was not able to attenuate the effects of pilocarpine. The molecular mechanisms underlying taurine action on behavioral and electrophysiological parameters in the normal and altered brain remain to be further explored.

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“…Several studies have also investigated pharmacotherapeutic response in SE animals using FDG-PET parameters. A study showed that blocking serotonin did not prevent decreased metabolism and subsequent cell death post-SE [87,88]. Other studies have showed that short-term decreased metabolism can be prevented with fluoxetine treatment.…”

Section: Pet and Spect Subtypes In Preclinical Models Of Epilepsymentioning

confidence: 99%

“…Other studies have showed that short-term decreased metabolism can be prevented with fluoxetine treatment. A recent study determined that metyrapone treatment before SE is neuroprotective and prevents decreased metabolic activity post-SE [86,87,88]. In a genetic model of epilepsy in rats, acute vagus nerve stimulation was found to decrease hippocampal FDG uptake, correlating with increased duration of EEG spike wave duration [99,100].…”

Section: Pet and Spect Subtypes In Preclinical Models Of Epilepsymentioning

confidence: 99%

Neuroimaging Biomarkers of Experimental Epileptogenesis and Refractory Epilepsy

Reddy

Younus

Sridhar

et al. 2019

IJMS

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This article provides an overview of neuroimaging biomarkers in experimental epileptogenesis and refractory epilepsy. Neuroimaging represents a gold standard and clinically translatable technique to identify neuropathological changes in epileptogenesis and longitudinally monitor its progression after a precipitating injury. Neuroimaging studies, along with molecular studies from animal models, have greatly improved our understanding of the neuropathology of epilepsy, such as the hallmark hippocampus sclerosis. Animal models are effective for differentiating the different stages of epileptogenesis. Neuroimaging in experimental epilepsy provides unique information about anatomic, functional, and metabolic alterations linked to epileptogenesis. Recently, several in vivo biomarkers for epileptogenesis have been investigated for characterizing neuronal loss, inflammation, blood-brain barrier alterations, changes in neurotransmitter density, neurovascular coupling, cerebral blood flow and volume, network connectivity, and metabolic activity in the brain. Magnetic resonance imaging (MRI) is a sensitive method for detecting structural and functional changes in the brain, especially to identify region-specific neuronal damage patterns in epilepsy. Positron emission tomography (PET) and single-photon emission computerized tomography are helpful to elucidate key functional alterations, especially in areas of brain metabolism and molecular patterns, and can help monitor pathology of epileptic disorders. Multimodal procedures such as PET-MRI integrated systems are desired for refractory epilepsy. Validated biomarkers are warranted for early identification of people at risk for epilepsy and monitoring of the progression of medical interventions.

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Metyrapone prevents brain damage induced by status epilepticus in the rat lithium-pilocarpine model

Cited by 23 publications

References 63 publications

The Neuroprotective Effect of Astaxanthin on Pilocarpine-Induced Status Epilepticus in Rats

The Neuroprotective Effect of Astaxanthin on Pilocarpine-Induced Status Epilepticus in Rats

Taurine/Pilocarpine Interaction in the Malnourished Rat Brain: A Behavioral, Electrophysiological, and Immunohistochemical Analysis

Neuroimaging Biomarkers of Experimental Epileptogenesis and Refractory Epilepsy

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