Project description

Epilepsy, being one of the oldest conditions known to mankind and the most common neurological disorder affecting individuals of all ages, is characterized by recurrent unprovoked seizures. In around 40% of epilepsy cases, disease etiology is known and the most frequent causes of acquired epilepsies are brain insults including traumatic brain injury, ischemic stroke, intracerebral hemorrhage, infections, tumors, cortical dysplasia, neurodegenerative diseases, and prolonged acute symptomatic seizures. Although people at risk of epilepsy can be identified, there is still no prophylactic treatment that would prevent the development of the disease.

Despite continued advancements in anticonvulsant development, approximately 30% of patients with epilepsy have refractory seizures, and so remains a significant demand for additional solutions. A growing body of evidence demonstrates that dietary therapies for this disease (classic ketogenic diet, medium-chain triglyceride diet, modified Atkins diet and low-glycemic-index treatment) are highly effective, with approximately 30-60% of children overall having at least a 50% reduction in seizures after 6 months of treatment. All these dietary therapies share the common characteristic of restricting carbohydrate intake to shift the predominant caloric source of the diet to fat. Catabolism of fats results in the production of ketone bodies which are alternate energy substrates to glucose. Although many mechanisms by which ketone bodies yield its anticonvulsant effect are proposed, the relationships between the brain metabolism of the ketone bodies and their neuroprotective and antiepileptogenic action still remain to be discerned.

The following project will be realized in cooperation with the Department of Neuroanatomy (Institute of Zoology, Jagiellonian University) and two European synchrotron facilities: ANKA (Karlsruhe, Germany) and SOLEIL (Gif sur Yvette, France), and will be the first part of our research under the mechanisms of neuroprotective action of ketogenic diet in case of epilepsy. The influence of ketogenic diet on the elemental and biochemical composition of rat hippocampal formation as well as on the chemical state of blood iron will be analyzed through the comparison of animals on high fat and standard laboratory diet. Moreover, it will be examined how the diet modifies the vulnerability to seizures and their progress in case of pilocarpine model of this disease. Analysis of the influence of ketogenic diet on the elemental and biochemical anomalies recorded for the acute phase of pilocarpine induced status epilepticus will help to understand the mechanisms of its action in epileptic brain and the same will significantly influence the progress in research under the use of ketogenic diet in humans as a neuroprotective factor increasing survival of neurons in different pathological conditions.