Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models

Samala, Ramakrishna; Willis, Stephen M.; Borges, Karin

doi:10.1016/j.eplepsyres.2008.05.001

Cited by 58 publications

(76 citation statements)

References 30 publications

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“…Similarly, interleukin 1 receptor antagonist inhibited epileptiform discharges found after activation of TLR4 receptors by lipopolysaccharide in naïve rats [11]. Also, ketones that are produced while on a ketogenic diet are anti-oxidant [25] and the ketogenic diet is anticonvulsant in the acute 6 Hz model [19,26], indicating that antioxidant or anti-inflammatory substances can protect against seizures in healthy brains without evident oxidative stress or inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Corneal stimulations (50 Hz sine waves, 0.2 s duration starting at 11 mA) were generated by a Hugo Sachs Type 211 rodent shocker (Harvard Apparatus, Germany) with 1 mA increments to determine the MEST using the up down method [19,20].…”

Section: Maximal Electroshock Threshold (Mest) Testmentioning

confidence: 99%

“…Using the "up-and-down" method, electrical currents were applied to different mice with 2 mA intervals to determine the critical current intensity needed to induce seizures in 50% of CD1 mice (CC50) [19].…”

Section: Hz Modelmentioning

confidence: 99%

“…The PTZ doses needed to induce the first twitch, first myoclonic seizure and tonic extension of the hind limbs were measured [19].…”

Section: Genementioning

confidence: 99%

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Anticonvulsant screening of luteolin in four mouse seizure models

Shaikh

Tan

Borges

2013

Neuroscience Letters

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Section: Discussionmentioning

confidence: 99%

Section: Maximal Electroshock Threshold (Mest) Testmentioning

confidence: 99%

Section: Hz Modelmentioning

confidence: 99%

“…The PTZ doses needed to induce the first twitch, first myoclonic seizure and tonic extension of the hind limbs were measured [19].…”

Section: Genementioning

confidence: 99%

See 2 more Smart Citations

Anticonvulsant screening of luteolin in four mouse seizure models

Shaikh

Tan

Borges

2013

Neuroscience Letters

Self Cite

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“…Corneal electroshocks from a rodent electroshock unit (Ugo Basile, Varese, Italy; 6 Hz, 3 s, 0.2 millisecond rectangular pulse width) were given starting at 14 mA (Samala et al, 2008). Using the up down method we determined the critical current at which 50% of mice seized (Thomas et al, 2012).…”

Section: Liquid Chromatography Tandem Mass Spectrometry (Lc-ms/ms)mentioning

confidence: 99%

The role of complement in epilepsy: a specific focus on C5ar1 and its role in seizure initiation and disease development

Benson¹

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Neuroinflammation and its role in seizure initiation and epilepsy disease development is being investigated, specifically the role of innate immune complement activation through the C5a receptor, C5ar1.C5ar1 expression was found to be significantly upregulated during epilepsy disease progression in several experimental mouse models, in addition to other complement components such as C3, the precursor to C5a. Building upon existing studies supporting the role of inflammation and other complement components in epilepsy, this finding indicates a contribution of C5a and complement activation in this disease. This lead to creation of the primary hypothesis of this thesis; inhibition of C5ar1 activation is potentially neuroprotective and anticonvulsant in epilepsy.To test this hypothesis a small peptide antagonist of C5ar1, PMX53, was used. It was shown to be anticonvulsant in two acute and two chronic seizure models. PMX53 increased the seizure threshold significantly in both the 6Hz test and the corneal kindling model, as well as reduced EEG seizure power in the pilocarpine-induced SE model, indicating anticonvulsant actions. Studies using the chronic intrahippocampal kainate model combined with EEG, showed that PMX53 was acutely anticonvulsant after a single peripheral administration, significantly reducing total time in seizure by >50% as well as EEG seizure power. In addition, treatment of mice with PMX53 during pilocarpine-SE lead to a vast reduction in EEG seizure power highlighting further anticonvulsant effects. These results suggest inhibition of C5ar1 is beneficial in increasing seizure thresholds in several mouse models of epilepsy.Further studies using inert structural analogues of PMX53 and C5ar1-deficient mice in the 6Hz model showed that PMX53's anticonvulsant effect is C5ar1-dependent. This confirms my hypothesis that antagonism of C5ar1 is anticonvulsant. To determine if C5ar1-mediated anticonvulsant effects lead to changes in subsequent cellular damage, neuronal cell death in the hippocampal formation was evaluated acutely after pilocarpine-induced SE. In both PMX53-treated animals and mice lacking the C5ar1 receptor, significant reductions in neuronal degeneration and loss were evident in key hippocampal areas including CA1 and CA3 pyramidal cell layers.iii In addition, the explicit role of C5ar1 expression on microglial cells was investigated, given that consistent upregulation of the receptor was shown at varying stages post-epileptic insult in mice. Specifically microglial activation phenotypes were assessed, based on expression patterns of inflammatory and activation markers. M1 phenotype is considered to be more inflammatory in nature and is detected through expression of pro-inflammatory cytokines, i.e. IL-1β, TNFα, IL-6 and classical activation markers, i.e. CD16, CD86. M2 phenotype is defined as being more reparative in nature, with markers such as Arginase1 (Arg1) and Chitinase-like-3 (Ym1) being associated with this phenotype, all linked to different aspects of cell repair, as wel...

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Ketogenic Diet Based on Extra Virgin Coconut Oil Has No Effects in Young Wistar Rats With Pilocarpine‐Induced Epilepsy

Melo

Rêgo

Bueno

et al. 2018

Lipids

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This study evaluated the effects of a ketogenic diet (KD) based on extra virgin coconut oil (Cocos nucifera L., VCO), on the treatment of epileptic rats. Two sets of experiments were conducted. First, male Wistar rats underwent induction of status epilepticus (SE) with the administration of pilocarpine intraperitoneally 21 animals reached spontaneous recurrent seizures (SRS) and were randomly allocated to the dietary regimens and video-monitored for 19 days. In the second experiment, 24 animals were randomized immediately after the induction of SE and followed for 67 days. Diets were as follows: Control (AIN-93G; 7% lipid), KetoTAGsoya (KD based on soybean oil; 69.79% lipid), and KetoTAGcoco (KD based on VCO; 69.79% lipid). There were no differences in the latency to the first crisis, total frequency, and duration of the SRS between groups in 2 experiments. The data suggest no effects of KD, with or without VCO, in rats with pilocarpine-induced epilepsy.

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Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models

Cited by 58 publications

References 30 publications

Anticonvulsant screening of luteolin in four mouse seizure models

Anticonvulsant screening of luteolin in four mouse seizure models

The role of complement in epilepsy: a specific focus on C5ar1 and its role in seizure initiation and disease development

Ketogenic Diet Based on Extra Virgin Coconut Oil Has No Effects in Young Wistar Rats With Pilocarpine‐Induced Epilepsy

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