A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice

一种新的生酮配方可改善成年小鼠脑外伤后的功能结果并减少组织损失

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作者:Orli Thau-Zuchman, Linda Svendsen, Simon C Dyall, Ursula Paredes-Esquivel, Molly Rhodes, John V Priestley, René G Feichtinger, Barbara Kofler, Susanne Lotstra, J Martin Verkuyl, Robert J Hageman, Laus M Broersen, Nick van Wijk, Jose P Silva, Jordi L Tremoleda, Adina T Michael-Titus

Conclusion

The behavioural improvement and tissue protection provide proof of principle that this new formulation has therapeutic potential in adult TBI.

Methods

We designed a new-KD with a fat to carbohydrate plus protein ratio of 2:1, containing medium chain triglycerides (MCT), docosahexaenoic acid (DHA), low glycaemic index carbohydrates, fibres and the ketogenic amino acid leucine, and evaluated its neuroprotective potential in adult TBI. Adult male C57BL6 mice were injured by controlled cortical impact (CCI) and assessed for 70 days, during which they received a control diet or the new-KD.

Results

The new-KD, that markedly increased plasma Beta-hydroxybutyrate (β-HB), significantly attenuated sensorimotor deficits and corrected spatial memory deficit. The lesion size, perilesional inflammation and oxidation were markedly reduced. Oligodendrocyte loss appeared to be significantly reduced. TBI activated the mTOR pathway and the new-KD enhanced this increase and increased histone acetylation and methylation.

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