Ketogenic diet reduces Smac/Diablo and cytochrome c release and attenuates neuronal death in a mouse model of limbic epilepsy

Luan, Guoming; Zhao, Yanxin; Zhai, Feng; Chen, Yin; Li, Tianfu

doi:10.1016/j.brainresbull.2012.07.002

Cited by 18 publications

(15 citation statements)

References 35 publications

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“…Fluorescein‐based terminal deoxynucleotidyltransferase‐mediated dUTP nick end‐labeling (TUNEL) (Roche Molecular Biochemicals, Indianapolis, IN) was used for the detection of DNA fragmentation as described previously .…”

Section: Methodsmentioning

confidence: 99%

“…For the semiquantitative immunohistochemical detection of GLT‐1, Bcl‐2 and CD73, we followed our previously published procedures with modifications . Two sections from RE patients (n = 18) and controls (n = 6) each were analyzed by scanning GLT‐1 and bcl‐2 immunoreactivity on DAB‐stained slices and the mean area for quantitative analysis was a 2 × 3 mm 2 field using a Kodak imaging device.…”

Section: Methodsmentioning

confidence: 99%

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Upregulation of adenosine A2A receptor and downregulation of GLT1 is associated with neuronal cell death in Rasmussen's encephalitis

Chen

Zhang

et al. 2019

Brain Pathology

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Rasmussen encephalitis (RE) is a severe pediatric inflammatory brain disease characterized by unilateral inflammation and atrophy of the cerebral cortex, drug‐resistant focal epilepsy and progressive neurological and cognitive deterioration. The etiology and pathogenesis of RE remain unclear. Our previous results demonstrated that the adenosine A1 receptor (A1R) and the major adenosine‐removing enzyme adenosine kinase play an important role in the etiology of RE. Because the downstream pathways of inhibitory A1R signaling are modulated by stimulatory A2AR signaling, which by itself controls neuro‐inflammation, glial activation and glial glutamate homeostasis through interaction with glutamate transporter GLT‐1, we hypothesized that maladaptive changes in adenosine A2A receptor (A2AR) expression are associated with RE. We used immunohistochemistry and Western blot analysis to examine the expression of A2ARs, glutamate transporter‐I (GLT‐1) and the apoptotic marker Bcl‐2 in surgically resected cortical specimens from RE patients (n = 18) in comparison with control cortical tissue. In lesions of the RE specimen we found upregulation of A2ARs, downregulation of GLT‐1 and increased apoptosis of both neurons and astroglia. Double staining revealed colocalization of A2ARs and Bcl‐2 in RE lesions. These results suggest that maladaptive changes in A2AR expression are associated with a decrease in GLT‐I expression as a possible precipitator for apoptotic cell loss in RE. Because A2AR antagonists are already under clinical evaluation for Parkinson's disease, the A2AR might likewise be a tractable target for the treatment of RE.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Upregulation of adenosine A2A receptor and downregulation of GLT1 is associated with neuronal cell death in Rasmussen's encephalitis

Chen

Zhang

et al. 2019

Brain Pathology

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“…There is strong evidence that the KD effectively controls seizures in patients with DS (Caraballo, 2011;Caraballo et al, 2005;Kang et al, 2005;Korff et al, 2007;Laux and Blackford, 2013), especially when added to the gold standard triple combination (Nabbout et al, 2011). Further, the diet has been reported to exhibit neuroprotective effects (Dutton et al, 2011;Luan et al, 2012) and to control long lasting SE refractory to conventional AED treatment (Nabbout et al, 2010).…”

Section: Introductionmentioning

confidence: 94%

Efficacy and tolerability of the ketogenic diet in Dravet syndrome – Comparison with various standard antiepileptic drug regimen

et al. 2015

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“…The protein concentration from the cytosol (supernatant) was determined spectrophotometrically from the absorbance at 595 nm (A595 nm) using the Bradford method (22). Samples (80 μg) were denatured in gel-loading buffer and separated on 15% SDS-PAGE gels, then transferred to polyvinylidene difluoride membranes and incubated with the following primary antibodies: Rabbit polyclonal anti-XIAP (1:500 dilution; Abcam), rabbit polyclonal antibody raised against Smac (1:500 dilution; Chemicon, Temecula, CA, USA), rabbit polyclonal antibody raised against cyto c (1:200 dilution; Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA), rabbit anti-β-actin (1:1,500 dilution; Sangon Biotech, Shanghai, China) and goat anti-rabbit IgG conjugated to horseradish peroxidase (1:800 dilution; ZSGB-BIO, Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

Radiation-induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z-VAD-fmk in the hypoglossal nucleus

Wang

et al. 2013

Experimental and Therapeutic Medicine

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Numerous studies have demonstrated that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase activation fundamentally via the mitochondrial pathway. To investigate the role of caspase, a cell permeable pan-caspase inhibitor, z-VAD-fmk [N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone], was used to investigate the effects of caspase blockade in vivo following irradiation. Adult male Sprague-Dawley rats (weight, 250–300 g) underwent irradiation at room temperature with a 4-Gy dose of radiation. Since z-VAD-fmk does not penetrate the blood-brain barrier, it was applied intracerebroventricularly via a bolus injection (0.2 μg/h for 1 h). Terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) demonstrated that z-VAD-fmk reduced the numbers of TUNEL-positive cells within the hypoglossal nucleus, suggesting that intervention in the caspase cascade following radiation may have therapeutic applications. The caspase inhibitor z-VAD-fmk reduced the expression and activation of caspase-3, caspase-8 and caspase-9 in the irradiated rats, indicating that caspase may be a potential therapeutic target in the treatment of brain radiation injury. Treatment with z-VAD-fmk also reduced the appearance of cytochrome c within the cytosolic fraction following radiation. The hypoglossal nucleus may be used as a model of radiation-induced injury in the central nervous system, providing visual information and displaying apoptotic nuclear morphology.

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Ketogenic diet reduces Smac/Diablo and cytochrome c release and attenuates neuronal death in a mouse model of limbic epilepsy

Cited by 18 publications

References 35 publications

Upregulation of adenosine A2A receptor and downregulation of GLT1 is associated with neuronal cell death in Rasmussen's encephalitis

Upregulation of adenosine A2A receptor and downregulation of GLT1 is associated with neuronal cell death in Rasmussen's encephalitis

Efficacy and tolerability of the ketogenic diet in Dravet syndrome – Comparison with various standard antiepileptic drug regimen

Radiation-induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z-VAD-fmk in the hypoglossal nucleus

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