A Ketogenic Diet Increases the Resistance to Pentylenetetrazole‐Induced Seizures in the Rat

Bough, Kristopher J.; Eagles, Douglas A.

doi:10.1111/j.1528-1157.1999.tb02066.x

Cited by 136 publications

(106 citation statements)

References 22 publications

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“…Additionally, the onset time of seizures was prolonged in a KA-induced seizure model following BHB pretreatment in the present study, even though the degree of seizure behavior was not significantly decreased. This is consistent with previous findings demonstrating that KD increased the seizure threshold in rats but did not alleviate seizure severity (20). More experiments are still needed to verify the findings of the present study.…”

Section: Discussionsupporting

confidence: 83%

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Anticonvulsant effect of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy

Wang

Liu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to investigate the anticonvulsant effects of β-hydroxybutyrate (BHB) in a kainic acid (KA)-induced rat seizure model. The concentrations of BHB and glucose were detected in the blood prior to exogenous BHB administration. Three different doses of BHB (2, 4 and 8 mmol/kg) were then injected into male Wistar rats intraperitoneally, and the concentrations of BHB and glucose in the blood were detected. Rats received 0.9% normal saline intraperitoneally at a dose of 4 ml/kg as a control. Subsequently, a KA-induced rat seizure model was established and the anticonvulsant effects of BHB were investigated. The onset time of seizure and the degree of seizure behavior were recorded. Nissl and Timm staining were used to evaluate neuronal loss and mossy fiber sprouting, respectively. The present study demonstrated that exogenous BHB administration could significantly increase BHB concentration in the blood and this concentration was maintained for 90 min without affecting blood glucose levels. Furthermore, it was determined that a dose of 4 mmol/kg BHB is optimal for exogenous administration. The onset time of seizure was significantly prolonged in BHB-pretreated rats (63.31±4.050 min) compared with the control group (37.08±1.958 min; P=0.039). In addition, neuronal loss and mossy fiber sprouting were both alleviated in the BHB-pretreated model group. Exogenous BHB administration at a dose of 4 mmol/kg may be an alternative to a ketogenic diet to exert a protective effect in the epileptic model induced by KA. The results of the present study may allow novel therapeutic strategies to be developed to treat epilepsy.

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Section: Discussionsupporting

confidence: 83%

“…Furthermore, KD can increase the BHB level significantly and rats on KD had a significantly increased threshold for seizure induction (20). Furthermore, KD is not antiepileptic until BHB levels in the blood reach an efficacious level (1-2 mmol/l in rats) (14).…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsant effect of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy

Wang

Liu

et al. 2017

Experimental and Therapeutic Medicine

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“…Anticonvulsant agents that target the GABA system are usually only weakly effective in the maximal electroshock test and some are ineffective. In contrast, the ketogenic diet was found to be protective in the pentylenetetrazol test in rats [25][26][27][28]. The diet also was effective against seizures induced by the GABA A receptor antagonists bicuculline and picrotoxin in rats [31], but did not confer sustained protection against fully kindled seizures in the rat amygdala kindling model [21,22].…”

Section: Gaba Systemsmentioning

confidence: 99%

The Neuropharmacology of the Ketogenic Diet

Hartman

Gąsior

Vining

et al. 2007

Pediatric Neurology

280

169

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The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which most clinical experience has been with children. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. The pattern of protection of the ketogenic diet in animal models of seizures is distinct from that of other anticonvulsants, suggesting that it has a unique mechanism of action. During consumption of the ketogenic diet, marked alterations in brain energy metabolism occur, with ketone bodies partly replacing glucose as fuel. Whether these metabolic changes contribute to acute seizure protection is unclear; however, the ketone body acetone has anticonvulsant activity and could play a role in the seizure protection afforded by the diet. In addition to acute seizure protection, the ketogenic diet provides protection against the development of spontaneous recurrent seizures in models of chronic epilepsy, and it has neuroprotective properties in diverse models of neurodegenerative disease.

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“…A ketogenic diet with a ratio of fat to carbohydrate plus protein of 6.3:1 has been used extensively in animal experiments designed to examine the anticonvulsant properties of the diet (standard diet) (17,18). This diet's ratio of 6.3:1, however, is significantly higher than the ratio of 3:1 or 4:1 commonly used in patients who are treated with the ketogenic diet (15).…”

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confidence: 98%

Effect of the Ketogenic Diet on the Activity Level of Wistar Rats

et al. 2005

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Children, adolescents, and adults with epilepsy often also show symptoms associated with attention-deficit/hyperactivity disorder (ADHD). The ketogenic diet, which is administered to children with epilepsy refractory to drug therapy, seems to improve behavior in individuals with symptoms of ADHD. The basis for this improvement is unknown, although it seems to be unrelated to seizure control. The present research was designed to investigate the effect of two ketogenic diets on the behavior of normal adult male rats. Two experiments were conducted. In experiment 1, 36 subjects were placed on one of three diets: a control diet, a 6.3:1 ketogenic diet, and a 4:1 ketogenic diet. In experiment 2, 20 subjects were placed either on a control diet or on a 4:1 ketogenic diet. The activity level of each subject was measured using an open field test. Time spent immobile, grooming, and in exploratory behavior was measured for 600 s. Subjects were tested once before initiation of the diets and once while on the diets. No significant group differences were found in activity level before initiation of the diets. After initiation of the diets, subjects in both ketogenic groups showed a significantly lower activity level than the rats on the control diet. The ketogenic diet decreases activity level in an animal model. This behavioral change may relate to the improved behavior seen when children with symptoms of ADHD are placed on the diet. Attention-deficit/hyperactivity disorder (ADHD) affects children, adolescents, and adults. The symptoms of the disorder include inattentiveness, impulsiveness, and overactivity (1). The cause of the disorder is unknown, although there is evidence that it is, in part, heritable (2-4). The most common treatment for ADHD is stimulant medication.Regardless of whether they meet DSM-IV (1) criteria for the disorder, children and adults with epilepsy often exhibit symptoms of ADHD (5-10). Both anecdotal reports (6,11) and controlled studies (12) suggest that the ketogenic diet ameliorates symptoms of ADHD in individuals with epilepsy. Attention (6,11), cognition (12,13), and behavior (6,11,12) have been reported to improve in individuals who have epilepsy and are on the ketogenic diet. The improvement in these domains seems to be unrelated to the level of seizure control attained (6).The ketogenic diet is a high-fat, low-carbohydrate, and low-protein diet (14,15). It is an effective treatment for intractable epilepsy (5,11,12) and has been found to be useful in controlling seizures that have proved to be unresponsive to drug treatment in both children and adults (15,16). The ketogenic diet has also been found to be effective in animal studies. It increases seizure threshold in several animal models of epilepsy (17)(18)(19). Although the mechanism by which the diet controls seizures is unknown, it is thought that the low level of carbohydrate in the diet forces the brain to take up ketone bodies instead of glucose as a fuel (15,20,21).In the present research, the effect of two different ketogenic diets...

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A Ketogenic Diet Increases the Resistance to Pentylenetetrazole‐Induced Seizures in the Rat

Cited by 136 publications

References 22 publications

Anticonvulsant effect of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy

Anticonvulsant effect of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy

The Neuropharmacology of the Ketogenic Diet

Effect of the Ketogenic Diet on the Activity Level of Wistar Rats

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