Associated prognostic impact of opioid use before Transcatheter aortic valve implantation - A Danish nationwide cohort study.

The ketogenic diet (KD) is a specialized dietary intervention characterized by high fat content, low carbohydrate intake, and appropriate proportions of protein and other essential nutrients. Since its formal integration into epilepsy management in the 20th century, KD has consistently demonstrated therapeutic efficacy and is now widely recognized as a first-line non-pharmacological treatment for drug-resistant epilepsy (, , ). Clinical evidence indicates that KD reduces seizure frequency by > 50% in 95% of children with drug-resistant epilepsy, with 80% of these patients achieving a > 90% reduction in seizure burden (). Beyond generalized drug-resistant epilepsy, KD confers beneficial effects in several early-onset refractory epileptic encephalopathies, including Dravet syndrome (, ), Doose syndrome (, ), and West syndrome (). Nevertheless, a subset of pediatric patients with drug-resistant epilepsy remains non-responsive to KD treatment. In contrast to traditional carbohydrate-centric diets, KD primarily relies on ketone bodies—end products of fat metabolism—as the primary energy source for the central nervous system. Following KD initiation, plasma levels of ketone bodies, insulin, glucose, glucagon, and free fatty acids undergo profound metabolic alterations (). These metabolic shifts are thought to inhibit excessive neuronal excitability and aberrant discharges, stabilize synaptic function, and thereby mitigate epileptic seizures (, , ). However, the precise metabolic remodeling and underlying molecular mechanisms mediating KD’s anti-seizure effects remain incompletely elucidated, highlighting a critical gap in current knowledge. Zebrafish (Danio rerio) are widely used as experimental model organisms in biological research. Zebrafish larvae are increasingly employed to investigate the effects of gene manipulation or chemical exposure on physiology and behavior (, ). A key advantage of zebrafish lies in their developmental, structural, and pharmacological similarities to mammalian nervous systems. Specifically, their central nervous system (CNS) architecture closely resembles that of mammals, and they share conserved physiological and genetic properties with humans ; ). These characteristics render zebrafish particularly valuable for neurobiological studies. For instance, they are extensively utilized to study epileptogenesis and behavioral phenotypes during epileptic crises (, , , ). Additionally, zebrafish facilitate the identification of therapeutic targets and the development of novel anti-seizure medications (ASMs) (, , ). They also serve as a rapid and efficient screening tool for neuroactive and neurotoxic substances.