Ketogenic diet reduces spontaneous seizures and mossy fiber sprouting in the kainic acid model

Muller-Schwarze, Annette B.; Tandon, Pushpa; Liu, Zhao; Yang, Yili; Holmes, Gregory L.; Stafstrom, Carl E.

doi:10.1097/00001756-199905140-00023

Cited by 106 publications

(73 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was first demonstrated in 1999 by Muller-Schwarze et al [82], who found that rats fed a ketogenic diet had fewer and briefer spontaneous recurrent seizures after kainic acid-induced status epilepticus than did control animals. In a subsequent study it was found that early initiation of the diet is necessary to obtain this antiepileptogenic effect [83].…”

Section: Antiepileptogenic Activity Of the Ketogenic Dietmentioning

confidence: 85%

The Neuropharmacology of the Ketogenic Diet

Hartman

Gąsior

Vining

et al. 2007

Pediatric Neurology

280

169

View full text Add to dashboard Cite

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.

show abstract

Section: Antiepileptogenic Activity Of the Ketogenic Dietmentioning

confidence: 85%

The Neuropharmacology of the Ketogenic Diet

Hartman

Gąsior

Vining

et al. 2007

Pediatric Neurology

280

169

View full text Add to dashboard Cite

show abstract

“…Muller-Schwartze et al (40) found that administration of the KD after kainic acid-induced SE reduced both spontaneous seizure frequency and mossy fiber sprouting. Likewise, Noh et al (41) found that the KD inhibited apoptosis after kainic acid-induced SE.…”

Section: Discussionmentioning

confidence: 99%

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

et al. 2004

View full text Add to dashboard Cite

The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/ pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KDfed rats, with or without SE, had significantly impaired visualspatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development. The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is now widely used to treat epilepsy (1-4). Although the diet has not undergone the rigorous evaluation process required for marketing of antiepileptic drugs, there is now a considerable body of evidence indicating that the KD is efficacious in the treatment of epilepsy (1,2,5,6).Despite the use of the KD over several decades, the long-term effects of the KD on cognition are not yet known. Anecdotal reports suggest improvements in alertness, cognitive function, and behavior (2), although impairments in patients have also been reported (7). In a prospective study on the effects of the KD, Pulsifer et al. (8) found that developmental quotients in children on the diet improved after 1 y. One of the difficulties in evaluating cognitive effects of the KD in children is that the diet is rarely continued in children who do not respond with a reduction in seizure frequency (5, 9). The improvement in cognitive function therefore may represent the effects of reduced seizures, a positive cognitive effect of the diet, or a combination of these facto...

show abstract

“…Moreover, there is accumulating evidence from studies in models of chronic epilepsy that the ketogenic diet has antiepileptogenic properties that extend beyond its anticonvulsant efficacy. Thus, in the rat kainic acid model of temporal lobe epilepsy, the development of spontaneous seizures was attenuated by the ketogenic diet and there was a reduction in the severity of the seizures that did occur (Muller-Schwarze et al, 1999;Stafstrom et al, 1999;Su et al, 2000). In addition, animals fed the diet have reduced hippocampal excitability and decreased supragranular mossy fiber sprouting in comparison with rats fed a normal diet.…”

Section: Epilepsymentioning

confidence: 97%

Neuroprotective and disease-modifying effects of the ketogenic diet

Gąsior¹,

Rogawski²,

Hartman³

2006

Behavioural Pharmacology

401

324

View full text Add to dashboard Cite

The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially β-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury. This review summarizes the experimental, epidemiological and clinical evidence indicating that the ketogenic diet could have beneficial effects in a broad range of brain disorders characterized by the death of neurons. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet.

show abstract

Ketogenic diet reduces spontaneous seizures and mossy fiber sprouting in the kainic acid model

Cited by 106 publications

References 12 publications

The Neuropharmacology of the Ketogenic Diet

The Neuropharmacology of the Ketogenic Diet

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

Neuroprotective and disease-modifying effects of the ketogenic diet

Contact Info

Product

Resources

About