Presentation description
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, with 30% of patients resistant to therapies. Viral brain infections trigger neuroinflammation, a key driver of seizure development. The ketogenic diet (KD), a high-fat, low-carbohydrate diet, has shown promise in reducing seizures, particularly in drug-resistant epilepsy. While proposed mechanisms for its anti-seizure effects include modulation of mitochondrial function, inflammation, and gut microbiota, the precise mechanisms remain unclear, especially in infection-induced epilepsy.
To address these gaps, we will use a mouse model of viral-induced epilepsy. C57BL/6J mice infected with Theiler's murine encephalomyelitis virus (TMEV) develop acute seizures from 3-7 days post-infection (dpi), followed by a latent period and later chronic epilepsy. This model mimics temporal lobe epilepsy, a highly refractory form, and involves neuroinflammation and infiltration of inflammatory macrophages from the periphery into the brain. We hypothesized that KD attenuates seizures by reducing neuroinflammation, immune cell infiltration, and modulating the gut microbiome community. Mice (n=30/group) were fed KD or control diet 10 days before TMEV infection and remained on their respective diets throughout the experiment. Seizures were determined twice/daily from 3-7 dpi. Fecal samples were collected pre-infection and on day 7 for 16S rRNA sequencing. At 7dpi, brains were harvested for flow cytometry to assess immune cell infiltration and microglial activation, while hippocampi and plasma were used for cytokine profiling. This study will determine whether KD is an effective treatment option for viral-induced epilepsy and will provide crucial insights into the mechanisms by which KD modulates inflammation and seizures.
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