Abstracts

Rationale: Inflammatory mechanisms are widely acknowledged as contributing to the pathogenesis of several neurodegenerative disorders including epilepsy. There is also increasing evidence that inflammatory processes might constitute a crucial mechanism in the pathophysiology of epilepsy. Furthermore, recent studies suggest that the ketogenic diet (KD) diminishes inflammation and cytokine release. In the present study, we examined brain levels of multiple inflammatory mediators (cytokines/chemokines) in Kcna1-null epileptic mice following treatment with regular rodent chow or the KD. Methods: Here, we used KD treatment (PMID: 25899847) hippocampal tissue collection after perfusion from C3HeB/FeJ wild-type and epileptic Kcna1-null mice with and without KD, discovery assay (cytokine/chemokine multiplex kit from Millipore; EVE Technologies, Calgary, AB), and immunohistochemical (IHC) labeling as previously described (PMID: 26119933 and PMID: 28609458). Results: We performed protein expression profiling of 32 inflammatory mediators using a multiplex bead-based immunoassay from the hippocampus of wild-type and epileptic Kcna1-null mice after KD treatment (n=3 per group, 4 among 32 inflammatory mediators were not detected; IL-3, IL-5, MIP-1a, and MIP-1b). In epileptic mice, we identified several inflammatory mediators that were up-regulated, four of which were close to reaching statistical significance compared to controls: IL-1a, IL-7, IL-12(p40), and IL-12(p70) (pKcna1-null mice but normalized after KD treatment. Conclusions: Taken together, our results are consistent with the notion that there is increased inflammation in epileptic brain, and suggest that the KD attenuates the neuroinflammation, at least in part by mitigating increased microglial/macrophage activation. Thus, the KD may exert some of its clinical anti-seizure effects through decreased inflammation. Funding: Alberta Children’s Hospital Research Institute & Alberta Children’s Hospital Foundation