Neuroregeneration improved by ketones

Ketone bodies serve as alternative fuel for the brain when glucose availability is limited. The ketone body beta‐hydroxybutyrate (BHB) is synthesized in the liver from acetoacetate, the first ketone produced in the fasting state. Several studies show that being in the state of ketosis can be neuroprotective, but the exact mechanism is not known. It is also not known whether ketones would aid regeneration of a nervous system injury. In this study we investigated on cell cultures whether ketone bodies improve neuroregeneration after injury or trauma. The effect of ketone bodies on cell regeneration was tested in 3 weeks old rat (Sprague Dawley) primary neuronal cell cultures. Scratch assay was performed for 24 hours, while the cells were either exposed to 2mM R, S‐sodium‐3‐hydroxibutyrate (BHB) or not (control). One hundred snapshots were taken with the CYTOSMART system to document the cell migration, changes in cell density and the process of cell regeneration into the damaged area over the 24 hours. Immunofluorescence reaction was performed to label beta III tubulin and synapsin I in the regenerating areas. Cell cultures treated with BHB showed more intense cell migration and regeneration of the damaged area over the 24 hour period. Significantly more DAPI stained cell nuclei were found in the damaged area in cell cultures with 2mM BHB at 20× (p=0.01)and at 10× (p=0.0004) magnification photos as well, and the cell coverage was higher than in control cell cultures. Markers that are associated with flagellar movement, cytoskeletal functions and axonogenesis, synaptogenesis were denser in treated neuronal cultures at the regeneration site as revealed by fluorescence microscopy. These above results show potential applications for ketogenic compounds for treating traumatic brain injury or other injury to the central nervous system.
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