image: Effects of KD on body weight and blood ketone levels in different groups of rats. (a) Experimental procedure flowchart: On the first day after SE, rats in the SE and N groups were fed either a KD or a normal diet for 7 or 20 days. Body weight and blood ketone levels were measured in the dietary intervention and control groups after 20 days of dietary intervention, followed by behavioral testing. Tissue specimens were collected at designated time points across all experimental groups. (b) Effect of KD intervention on body weight in rats (n = 7). (c) Effect of KD intervention on blood ketone levels in rats (n = 7). Values are expressed as the mean ± SEM. *: p < 0.05 and ***: p < 0.001. KD, ketogenic diet.
Credit: Pediatric Discovery
Status epilepticus (SE), a severe and prolonged form of seizure, often leaves lasting cognitive damage. In a new study, researchers explored whether the ketogenic diet (KD)—a high-fat, low-carbohydrate dietary regimen—could counteract this damage. Using a rat model, the team discovered that KD not only improved memory and learning abilities following SE, but also preserved brain structure. More importantly, the diet significantly reduced neuroinflammation by blocking the NF-κB signaling pathway, a key driver of inflammatory responses in the brain. These findings suggest that KD may do more than suppress seizures—it may actively protect the brain and restore cognitive function in the aftermath.
Epilepsy affects over 70 million people worldwide, and a significant portion of patients suffer from drug-resistant epilepsy (DRE), where standard medications fail. Beyond the seizures themselves, many patients face a hidden but devastating burden: cognitive decline, including memory loss and difficulty concentrating. These symptoms are believed to stem from underlying inflammation and structural brain damage. The ketogenic diet (KD) has long been used to manage seizures in DRE, but its potential to protect brain function remains underexplored. Due to these challenges, researchers are turning their focus toward understanding how KD might preserve cognitive abilities by addressing the root causes of neurological decline.
A research team at the Children's Hospital of Chongqing Medical University has published a study (DOI: 10.1002/pdi3.70013) in Pediatric Discovery (June 23, 2025), revealing how the KD can restore cognitive function following status epilepticus. The scientists used a well-established rat model to investigate changes in memory, behavior, brain structure, and inflammation. Central to their investigation was the NF-κB pathway—a master switch for inflammation in the brain—aiming to uncover whether KD’s protective effects are tied to suppression of this pathway and its downstream inflammatory responses.
In the study, juvenile rats were induced with SE using pilocarpine and then split into groups, with some receiving a KD for either 7 or 20 days. The researchers conducted a series of behavioral tests, including the Morris water maze and Y-maze, to assess memory and spatial learning. Rats fed with KD demonstrated notable improvements in exploratory behavior and cognitive performance compared to their non-treated counterparts.
Microscopic analysis revealed that KD-fed rats showed significantly less damage in the hippocampus—a brain region essential for memory. Neuronal density, myelin integrity, and axonal structure were all better preserved. This structural protection correlated with reduced levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α).
Molecular studies confirmed that KD suppressed activation of the NF-κB pathway, evident through decreased nuclear translocation of NF-κB p65 and reduced phosphorylation of IκB. These changes suggest that KD not only reduces inflammation but interrupts its signaling at the source. Together, the findings illustrate a two-pronged benefit: restoring memory and repairing brain damage—both mediated by curbing inflammation at the molecular level.
“Our research highlights a critical shift in how we view the KD—not just as a seizure-control therapy, but as a powerful tool for brain repair,” said Dr. Xiaojie Song, corresponding author of the study. “By dialing down inflammation at the cellular level, KD helps the brain recover from the long-term consequences of seizures. These results open up new possibilities for non-drug therapies that address both the seizures and the silent damage they leave behind. The future of epilepsy treatment may lie in the synergy of metabolic and molecular interventions.”
These findings offer exciting possibilities for expanding the role of the KD in neurological care. Beyond epilepsy, KD could emerge as a valuable intervention for other brain disorders marked by inflammation and cognitive decline, such as Alzheimer’s disease and traumatic brain injury. The ability to modulate the NF-κB pathway through dietary means opens a door to low-risk, non-invasive therapeutic strategies. Future research will need to explore how long these benefits last, the ideal duration of treatment, and whether combining KD with pharmacological agents could further amplify its effects—especially in vulnerable populations like children with DRE.
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References
DOI
Original Source URL
https://doi.org/10.1002/pdi3.70013
Funding information
This work was supported by the National Natural Science Foundation of China (81901260), Youth Research Project on Basic Research of Ministry of Education Key Laboratory of Child Development and Disorders (345 [2021]‐YBRP‐202116), and Youth Clinical Research Project of National Clinical Research Center for Child Health and Disorders (NCRCCHD‐2022‐YP‐0X).
About Pediatric Discovery
Pediatric Discovery is a Gold Open Access publication and peer-reviewed international journal. The journal aims to advance the health and well-being of infants, children, and adolescents by disseminating cutting-edge discovery and knowledge in the field. It provides a platform for publishing and discussing the most important and state-of-the-art basic, translational and clinical discoveries affecting child and adolescent health and disorders in all aspects of pediatric medicine. The journal has been indexed by DOAJ and PMC. . Currently, it does not charge any submission fees. The Article Publication Charge (APC) is currently waived for accepted manuscripts.
Journal
Pediatric Discovery
Subject of Research
Not applicable
Article Title
Protective Effects of the Ketogenic Diet on Cognitive Impairment Induced by Status Epilepticus in Rats: Modulation of Neuroinflammation Through the NF-κB Signaling Pathway
Article Publication Date
23-Jun-2025
COI Statement
The authors declare that they have no competing interests