Proton Magnetic Resonance Spectroscopy (H1-MRS) Study of the Ketogenic Diet on Repetitive Mild Traumatic Brain Injury in Adolescent Rats and Its Effect on Neurodegeneration.

OBJECTIVE: A ketogenic diet (KD) improves cellular metabolism and functional recovery after moderate-to-severe traumatic brain injury. Here, we evaluated the changes of neurochemical metabolites after KD therapy for repetitive mild traumatic brain injury (rmTBI) and its possible role in neurodegeneration.

METHODS: Postnatal day 35 rats were randomly divided into 3 groups: sham, control, and KD groups. Rats in control and KD groups were given 3 rmTBI by a fluid percussion traumatic brain injury device 24 hours apart. All rats were killed at 7 days after the last injury. The ipsilateral cortex were analyzed with hematoxylin and eosin staining; beta-hydroxybutyrate was measured; conventional magnetic resonance imaging and the dry-wet weight method were used to assess the brain edema; changes of neurochemical metabolites were assessed using the ratio of N-acetylaspartate (NAA)/creatine (Cr), choline compound (Cho)/Cr, and NAA/Cho with magnetic resonance spectroscopy; the effect of KD therapy on neurodegeneration was evaluated with double immunofluorescence staining of Iba-1/beclin-1; behavioral outcome was assessed with beam walk/beam balance tests.

RESULTS: KD significantly elevated beta-hydroxybutyrate levels, and there was no brain edema associated with rmTBI and KD therapy; behavioral assessment showed KD therapy significantly improved motor performance; magnetic resonance spectroscopy showed that rmTBI reduced the ratio of NAA/Cr and had no effect on the ratios of Cho/Cr and NAA/Cho whereas KD increased the ratio of NAA/Cr; double immunofluorescence staining showed KD therapy could significantly decrease microglial beclin-1 expression in the ipsilateral cortex.

CONCLUSIONS: These results suggest the effect of KD on metabolic status and its possible role in preventing neurodegeneration in adolescent rats after rmTBI.