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

Zhang, Fengchen; Wu, Hui; Jin, Yichao; Zhang, Xiaohua

doi:10.1016/j.wneu.2018.09.037

Cited by 18 publications

(20 citation statements)

References 46 publications

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“…Also, in blood collected from the heart immediately before perfusion, the level of bHb was significantly higher (Gzieło et al 2019 ). The glucose level remained normal, which was in agreement with Zhang et al ( 2018a , b ) who explained this fact as the result of adaptation to a long stay on a carbohydrate-free diet. Importantly, the morphotic blood elements were not affected, which suggests that these parameters were not modified when this diet was used in individuals suffering, for example, from epilepsy.…”

Section: Discussionsupporting

confidence: 91%

“…These studies showed only that the region-to-whole brain ratio of cerebral metabolic rate of glucose was 37–41% lower in the cortex and 40–45% lower in the cerebellum compared to cerebral metabolic rate of cerebral metabolic rate of acetoacetate in 4 month- and 21 month-old rats (Roya et al 2012 ). In the study by Zhang et al ( 2018a , b ), NAA, Cho, CR contents were assessed with MRI spectroscopy in animals fed a ketogenic diet after TBI. In addition, studies by Huang et al ( 2019 ) showed that KD applied for 3 months in mice did not cause changes in behavior when tested.…”

Section: Introductionmentioning

confidence: 99%

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MRI spectroscopic and tractography studies indicate consequences of long-term ketogenic diet

Gzieło¹,

Janeczko²,

Węglarz

et al. 2020

Brain Struct Funct

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To maintain its functional abilities, the mature brain obtains energy from glucose produced in carbohydrate metabolism. When carbohydrates are eliminated from the diet, the energy comes from the oxidation of fatty acids. In this metabolic state called ketosis, ketone bodies are formed: β-hydroxybutyric acid (bHb), acetone, and acetoacetate as alternative source of energy passing through the blood-brain barrier easily. The ketosis state can be achieved through various strategies like caloric restriction, supplementation with medium-chain triglycerides, intense physical training, or ketogenic diet (KD). Using KD, drug-resistant epilepsy has been successfully treated in children and adults. It can also exert neuroprotective influences in cases of brain damage, glioblastoma multiforme, and Alzheimer's or Parkinson's diseases. Although many possible mechanisms of KD activity have been proposed, newer hypotheses appear with the research progress, mostly characterizing the brain under pathological but not normal conditions. Since different pathological conditions may affect the mechanism of KD action differently, additional research on the normal brain appears reasonable. For this purpose, young adult rats were treated with 4-month-lasting KD. Then, MRI structural measurements, spectroscopy, and tractography were performed. The procedures revealed significant increases in the concentration of glutamine, glutamate, glutathione and NAA, accompanied by changes in the pattern of neuronal connections of the striatum and hippocampal formation. This implies a possible involvement of these structures in the functional changes occurring in the brain after KD application. Thus, the investigations on the normal brain add important details concerning mechanisms underlying KD effects without their possible modification by a pathological status.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

MRI spectroscopic and tractography studies indicate consequences of long-term ketogenic diet

Gzieło¹,

Janeczko²,

Węglarz

et al. 2020

Brain Struct Funct

View full text Add to dashboard Cite

show abstract

“…Indeed in 2013, we published a review suggesting some strong emerging evidence about the role of KD in different diseases (Paoli et al, 2013) which has been mostly confirmed so far. Many articles have been published indicating positive effects of KD on neurological diseases such as Alzheimer’s diseases (Ota et al, 2019; Taylor et al, 2018), ALS (Ari et al, 2014), brain trauma (concussion) (Zhang et al, 2018), migraine (Di Lorenzo et al, 2018), PCOS (Mavropoulos et al, 2005), and cancer (Klement, 2019). Moreover, new scenarios are opening such as the effects of BHB on epigenetics changes (Newman and Verdin, 2013; Ruan and Crawford, 2018), inflammation (Paoli et al, 2015b) and microbiota (Olson et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Ketogenic Diet and Skeletal Muscle Hypertrophy: a Frenemy Relationship?

Paoli

Cancellara

Pompei

et al. 2019

Journal of Human Kinetics

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Ketogenic diet (KD) is a nutritional regimen characterized by a high-fat and an adequate protein content and a very low carbohydrate level (less than 20 g per day or 5% of total daily energy intake). The insufficient level of carbohydrates forces the body to primarily use fat instead of sugar as a fuel source. Due to its characteristic, KD has often been used to treat metabolic disorders, obesity, cardiovascular disease, and type 2 diabetes. Skeletal muscle constitutes 40% of total body mass and is one of the major sites of glucose disposal. KD is a well-defined approach to induce weight loss, with its role in muscle adaptation and muscle hypertrophy less understood. Considering this lack of knowledge, the aim of this review was to examine the scientific evidence about the effects of KD on muscle hypertrophy. We first described the mechanisms of muscle hypertrophy per se, and secondly, we discussed the characteristics and the metabolic function of KD. Ultimately, we provided the potential mechanism that could explain the influence of KD on skeletal muscle hypertrophy.

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“…It has been reported that an 8-week KD may remodel the lipid metabolism profile, thus contributing to influence exercise capacity (33). Zhang et al showed that a ketogenic diet (KD) improved cellular metabolism and functional recovery after moderate traumatic brain injury in adolescent rats (34). These findings, combined with our present results, reinforce the importance of the lipid metabolism signals as an inducer of alterations in gene expression in the hippocampus and that such changes might contribute to the pathophysiology of the KD in brain disorders.…”

Section: Discussionmentioning

confidence: 99%

Neuro-Behavioral Status and the Hippocampal Expression of Metabolic Associated Genes in Wild-Type Rat Following a Ketogenic Diet

et al. 2019

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While a ketogenic diet (KD) is a well-established therapy for medically intractable epilepsy, clinical evidence of relevant adverse events of a KD has also been reported. We asked whether this kind of diet would have deleterious effects on wild-type brain function by evaluating KD-induced biochemical changes in the hippocampus as well as neurobehavioral changes occurring in wild-type rats. Fifty-four Sprague-Dawley rats were randomly assigned to three groups on postnatal day 28 (P28): wild-type rats fed with a KD qd (daily for 4 weeks, KD) or qod (every other day for 4 weeks, KOD), and wild-type rats fed with standard normal laboratory diet (ND). Neurobehavioral changes were observed on P35, P42, and P49. The hippocampal mossy fiber sprouting, the expression levels of zinc transporters (ZnTs) and lipid metabolism related genes were detected by Timm staining, RT-qPCR and western blot analysis, respectively, on P58. The KD-treated KOD and KD groups showed a significant delay of negative geotaxis reflex on P35, but not on P42 or P49. In the open field test, daily KD treatment only led to a reduction in exploratory activity and increased grooming times but induced no significant changes in the scores of vertical activity or delay time. KD qod treated rats (KOD) displayed a slight delay in the place navigation test on P35 compared with the KD group. There were no significant differences in Timm staining among the three groups. In parallel with these changes, KD treatment (both KD and KOD) induced significantly downregulated mRNA levels of Apoa1, Pdk4, and upregulated expression of ApoE, ANXN7, and cPLA2 in the hippocampus when compared with the ND group (except in the case of ApoE in the KOD group). Notably, both the mRNA and protein levels of cPLA2 in the KOD rats were significantly downregulated compared with the KD group but still markedly higher than in the ND group. No significant difference was found in ZnTs among the three groups. Our data suggest that early-life KD can provoke minor neurobehavioral effects in particular a delay in negative geotaxis reflex and an increase in grooming activity. The hippocampal lipid metabolism signaling pathway, especially cPLA2, may be the target of the protective effect of KD on long-term brain injury after developmental seizures.

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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

Cited by 18 publications

References 46 publications

MRI spectroscopic and tractography studies indicate consequences of long-term ketogenic diet

MRI spectroscopic and tractography studies indicate consequences of long-term ketogenic diet

Ketogenic Diet and Skeletal Muscle Hypertrophy: a Frenemy Relationship?

Neuro-Behavioral Status and the Hippocampal Expression of Metabolic Associated Genes in Wild-Type Rat Following a Ketogenic Diet

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