The behavioural and pathophysiological effects of the ketogenic diet on mild traumatic brain injury in adolescent rats

Salberg, Sabrina; Weerwardhena, Himanthri; Collins, Reid; Reimer, Raylene A.; Mychasiuk, Richelle

doi:10.1016/j.bbr.2019.112225

Cited by 29 publications

(23 citation statements)

References 85 publications

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“…The 49 articles finally selected were published over a four‐decade span (1979–2020) (Anson et al., 2003; Appelberg et al., 2009; Arumugam et al., 2010; Biros et Nordness, 1996; Bruce‐Keller et al., 1999; Davis et al., 2008; Duan et al., 2001; Eiger et al., 1980; Go et al., 1988; Gueldry et al., 1990; Hu, et al., 2009; Hu, Wang, Qiao, et al., 2009; Jeong et al., 2011; Kirsch et D’Alecy, 1979, 1983; Kirsch et al., 1980; Lee et al., 2018; Lu et al., 2018; Lundy et al., ,1984, 1985; Marie et a, 1987; Marie et al., 1990; Mayr et al., 2020; Plunet et al., ,2008, 2010; Prins et al., 2005; Prins et al., 2009; Puchowicz et al., 2008; Rahman et al., 2014; Rising et D’Alecy, 1989; Ritter et al., 1996; Robertson et al., 1992; Rubovitch et al., 2019; Salberg et al., 2019; Schwartzkroin et al., 2010; Sharma et Kaur, 2005; Sims et Heward, 1994; Streijger et al., ,2011, 2013; Suzuki et al., ,2001, 2002; Tai et al., 2008; Tai et Truong, 2007; Tan et al., 2020; Yager et al., 1992; Yamada et al., 2005; Yin et al., 2015; Yu et Mattson, 1999; Zahner et Beaumont, 2020). Details regarding publication, model, type of experiment, and intervention are available in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review ‐ Neuroprotection of ketosis in acute injury of the mammalian central nervous system: A meta‐analysis

Gambardella

Ascione

D’Agostino

et al. 2021

Journal of Neurochemistry

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The energy supply to neurons is provided by metabolic pathways that utilize oxygen and a caloric substrate. While the latter is predominantly glucose, the role of ketones may become relevant depending on species, age, caloric balance, diet composition, and pathophysiological state. Throughout the animal kingdom, the importance of ketone metabolism appears to be positively related to the brain/ body ratio (Cahill, 2006). In human infants, ketones provide 12.8% of the brain energy in a fed state, and 30% after 9 hr of fasting (Kraus

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Section: Resultsmentioning

confidence: 99%

Systematic Review ‐ Neuroprotection of ketosis in acute injury of the mammalian central nervous system: A meta‐analysis

Gambardella

Ascione

D’Agostino

et al. 2021

Journal of Neurochemistry

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“…The second study demonstrated that rats fasted for 24 h immediately post-concussion had elevated ketone bodies at 24 h, performed better on the Morris Water Maze task at 10 days, and had more cortical tissue at 15 days ( 31 ). Other studies suggest that acutely post-TBI, adolescent rats fed a KD have improved cortical contusion volume 1 week post-injury ( 49 ) and reduced anxiety and depression symptoms ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

The Ketogenic Diet in the Treatment of Post-concussion Syndrome—A Feasibility Study

2020

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Concussion is the most common form of mild traumatic brain injury (mTBI). Although most patients' symptoms resolve within a month, patients with post-concussion syndrome (PCS) may continue to experience symptoms for years and have limited treatment options. This pilot study assessed the feasibility and symptom-related effects of a ketogenic diet (KD) in patients with PCS symptoms. The Ketogenic Diet in Post-Concussion Syndrome (KD-PCS) was a single-arm trial of a 2-month KD high in non-starchy vegetables and supplemented with medium-chain triglyceride (MCT) oil. Macronutrient targets were ≥70% fat, ≤10% carbohydrate, and the remainder as protein as energy. We assessed feasibility by daily self-reported measure of urine acetoacetate and collection of 3-day food records and serum beta-hydroxybutyrate at multiple timepoints. We assessed symptoms by administering the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and Modified Balance Error Scoring System (M-BESS) at baseline and month 2 and the Post-Concussion Symptom Scale (PCSS) at baseline, month 1, and month 2. Fourteen participants enrolled in the KD-PCS. Twelve participants completed the study and 11 implemented the KD (73% fat, 9% carbohydrate, and 18% protein) and achieved ketosis. One participant complained of MCT-related diarrhea that resolved and another reported nausea and fatigue that resulted in withdrawal from the study. Among compliant participants, the visual memory domain of the ImPACT improved by 12 points (p = 0.02) and PCSS scores improved by 9 points, although not statistically significant. This pilot trial suggests that the KD is a feasible experimental treatment for PCS and justifies further study of its efficacy.

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“…This may suggest that secondary injury cascades accompanying TBI persist for days and even months following the initial injury, or that acute neuroinflammation causes chronic neurological changes, emphasizing the need to further characterize the temporal nature of cerebral vulnerability windows. In addition to these time-dependent effects, many environmental factors have been shown to influence the behavioral and molecular outcomes associated with RmTBI including sleep deprivation [ 41 ], diet (ketogenic diet: [ 42 ]; caffeine consumption [ 43 ]; monosodium glutamate (MSG) consumption [ 44 ]; alcohol consumption [ 45 ]), environmental enrichment [ 46 ], and exercise and anabolic steroid use [ 47 ]. Given the lack of knowledge surrounding cerebral vulnerability windows and the influence of various environmental factors on RmTBI pathophysiology during adolescence there is a significant need for future research in this area.…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Microglia dynamics in adolescent traumatic brain injury

Eyolfson

Khan

Mychasiuk

et al. 2020

J Neuroinflammation

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Repetitive, mild traumatic brain injuries (RmTBIs) are increasingly common in adolescents and encompass one of the largest neurological health concerns in the world. Adolescence is a critical period for brain development where RmTBIs can substantially impact neurodevelopmental trajectories and life-long neurological health. Our current understanding of RmTBI pathophysiology suggests key roles for neuroinflammation in negatively regulating neural health and function. Microglia, the brain’s resident immune population, play important roles in brain development by regulating neuronal number, and synapse formation and elimination. In response to injury, microglia activate to inflammatory phenotypes that may detract from these normal homeostatic, physiological, and developmental roles. To date, however, little is known regarding the impact of RmTBIs on microglia function during adolescent brain development. This review details key concepts surrounding RmTBI pathophysiology, adolescent brain development, and microglia dynamics in the developing brain and in response to injury, in an effort to formulate a hypothesis on how the intersection of these processes may modify long-term trajectories.

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The behavioural and pathophysiological effects of the ketogenic diet on mild traumatic brain injury in adolescent rats

Cited by 29 publications

References 85 publications

Systematic Review ‐ Neuroprotection of ketosis in acute injury of the mammalian central nervous system: A meta‐analysis

Systematic Review ‐ Neuroprotection of ketosis in acute injury of the mammalian central nervous system: A meta‐analysis

The Ketogenic Diet in the Treatment of Post-concussion Syndrome—A Feasibility Study

Microglia dynamics in adolescent traumatic brain injury

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