Objectives: To determine potential metabolism and histological modifications due to gadolinium retention within deep cerebellar nuclei (DCN) after linear gadolinium based contrast agent injection (gadodiamide) in rats at 1 year after the last injection. Materials and Methods: Twenty rats received 20 doses of gadodiamide (0.6 mmol of gadolinium per kilogram each) over 5 weeks. They were followed at 1 week (M0), 6 weeks (M1) and 54-55 weeks (M13) post-injections to evaluate hypersignal on unenhanced T1weighted MRI and metabolic alterations by 1 H MRS. At 1 year post-injections, brains were sampled to determine the localization of gadolinium within cerebellum by laser ablation inductively coupled mass spectroscopy (LA-ICP-MS) and to evaluate morphological changes by semi-quantitative immunofluorescence analysis. Results: There is a significant increase of the ratio DCN/brainstem for the gadodiamide group at M0 (+7.2% vs control group=0.989±0.01), M1 (+7.6% vs control group=1.002±0.018) and it lasted up to M13 (+4.7% vs control group=0.9862±0.008). No variation among metabolic markers (cellular homeostasis, excitatory neurotransmitter and metabolites specific to a cellular compartment) were detected by 1 H MRS between gadodiamide and saline groups at M0, M1 and M13. At M13, LA-ICP-MS demonstrated that long-term gadolinium retention occurred preferentially in DCN. No histological abnormalities (including analysis of astrocytes, neurons and microglial cells) were found in the rostral part of DCN. Conclusion: Repeated administration of gadodiamide lead to a retention of gadolinium preferentially within DCN until 1-year post-injections. This retention did not lead to any detectable changes of metabolic biomarkers nor histological alterations.

The ketogenic diet (KD) is an effective alternative treatment for refractory epilepsy in children, but the mechanisms by which it reduces seizures are poorly understood. To investigate how the KD modifies brain metabolism, we infused control (CT) and 7-day KD rats with either [1-13 C]glucose (Glc) or [2,4-13 C 2 ]β-hydroxybutyrate (β-HB). Specific enrichments of amino acids (AAs) measured by 1 H-and 13 C-NMR in total brain perchloric acid extracts were similar between CT and KD rats after [1-13 C]Glc infusion whereas they were higher in KD rats after [2,4-13 C 2 ]β-HB infusion. This suggests better metabolic efficiency of ketone body utilization on the KD. The relative rapid metabolic adaptation to the KD included (1) 11%-higher brain γ-amino butyric acid (GABA)/glutamate (Glu) ratio versus CT, (2) liver accumulation of the ketogenic branched-chain AAs (BCAAs) leucine (Leu) and isoleucine (ILeu), which were never detected in CT, and (3) higher brain Leu and ILeu contents. Since Glu and GABA are excitatory and inhibitory neurotransmitters, respectively, higher brain GABA/Glu ratio could contribute to the mechanism by which the KD reduces seizures in epilepsy. Increased BCAA on the KD may also contribute to better seizure control.

Alcopops are flavored alcoholic beverages sweetened by sodas, known to contain fructose. These drinks have the goal of democratizing alcohol among young consumers (12–17 years old) and in the past few years have been considered as fashionable amongst teenagers. Adolescence, however, is a key period for brain maturation, occurring in the prefrontal cortex and limbic system until 21 years old. Therefore, this drinking behavior has become a public health concern. Despite the extensive literature concerning the respective impacts of either fructose or ethanol on brain, the effects following joint consumption of these substrates remains unknown. Our objective was to study the early brain modifications induced by a combined diet of high fructose (20%) and moderate amount of alcohol in young rats by 13C Nuclear Magnetic Resonance (NMR) spectroscopy. Wistar rats had isocaloric pair-fed diets containing fructose (HF, 20%), ethanol (Et, 0.5 g/day/kg) or both substrates at the same time (HFEt). After 6 weeks of diet, the rats were infused with 13C-glucose and brain perchloric acid extracts were analyzed by NMR spectroscopy (1H and 13C). Surprisingly, the most important modifications of brain metabolism were observed under fructose diet. Alterations, observed after only 6 weeks of diet, show that the brain is vulnerable at the metabolic level to fructose consumption during late-adolescence throughout adulthood in rats. The main result was an increase in oxidative metabolism compared to glycolysis, which may impact lactate levels in the brain and may, at least partially, explain memory impairment in teenagers consuming alcopops.