title: Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity.
abstract: Cerebral metabolism of ketones after traumatic brain injury (TBI) improves neuropathology and behavior in an age-dependent manner. Neuroprotection is attributed to improved cellular energetics, although other properties contribute to the beneficial effects. Oxidative stress is responsible for mitochondrial dysfunction after TBI. Ketones decrease oxidative stress, increase antioxidants and scavenge free radicals. It is hypothesized that ketogenic diet (KD) will decrease post-TBI oxidative stress and improve mitochondria. Postnatal day 35 (PND35) male rats were given sham or controlled cortical impact (CCI) injury and placed on standard (STD) or KD. Ipsilateral cortex homogenates and mitochondria were assayed for markers of oxidative stress, antioxidant expression and mitochondrial function. Oxidative stress was significantly increased at 6 and 24 h post-injury and attenuated by KD while inducing protein expression of antioxidants, NAD(P)H dehydrogenase quinone 1 (NQO1) and superoxide dismutase (SOD1/2). Complex I activity was inhibited in STD and KD groups at 6 h and normalized by 24 h. KD significantly improved Complex II-III activity that was reduced in STD at 6 h. Activity remained reduced at 24 h in STD and unchanged in KD animals. These results strongly suggest that ketones improve post-TBI cerebral metabolism by providing alternative substrates and through antioxidant properties, preventing oxidative stress-mediated mitochondrial dysfunction.
authors.affiliation: Department of Neurosurgery, Los Angeles, CA, USA The UCLA Brain Injury Research Center, Los Angeles, CA, USA tgreco@mednet.ucla.edu.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Greco
authors.affiliation: Department of Neurosurgery, Los Angeles, CA, USA The UCLA Brain Injury Research Center, Los Angeles, CA, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Glenn
authors.affiliation: Department of Neurosurgery, Los Angeles, CA, USA The UCLA Brain Injury Research Center, Los Angeles, CA, USA The Interdepartmental Program for Neuroscience, Los Angeles, CA, USA Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
authors.affiliation: Department of Neurosurgery, Los Angeles, CA, USA The UCLA Brain Injury Research Center, Los Angeles, CA, USA The Interdepartmental Program for Neuroscience, Los Angeles, CA, USA.
authors.forename: Mayumi L
authors.initials: ML
authors.lastname: Prins
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000032:analysis; D001930:Brain Injuries / Q000178:diet therapy* / Q000378:metabolism; D055423:Diet, Ketogenic; D042963:Electron Transport Complex II / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000378:metabolism*; D005609:Free Radicals / Q000032:analysis; D007659:Ketones / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D013997:Time Factors
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D007659:Ketones; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III
keywords: Traumatic brain injury; juvenile; ketogenic diet; mitochondria; oxidative stress