Brain research
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Hypertonic saline is currently being used in the treatment of patients with post-traumatic cerebral edema and elevated intracranial pressure resulting from TBI. A limited number of studies show the cellular effects of hypertonic saline and no studies, to our knowledge, have investigated the effects on astrocytes. The role of astrocyte responses after traumatic brain injury remains unclear. ⋯ Plasma osmolarity and sodium levels were measured over 4 h and again at 24 h following hypertonic saline administration. Results show that hypertonic saline treatment reduced tissue loss that correlated with attenuated astrocyte hypertrophy characterized by reductions in astrocyte immunoreactivity without changes in the number of astrocytes after CCI injury. Delayed treatment of hypertonic saline resulted in the greatest reduction in tissue loss compared to all other treatments indicating that there is a therapeutic window for hypertonic saline use after traumatic brain injury.
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Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists play important roles in the regulation of energy metabolism and are widely used for patients with type 2 diabetes. PPARgamma agonists reportedly reduce plasma glucose levels by recruiting glucose transporters to the cellular membrane, resulting in the enhanced uptake of glucose. However, only a limited number of studies have examined the effect of PPARgamma on cerebral glucose metabolism. ⋯ These actions of pioglitazone were not inhibited by 2-chloro-5-nitrobenzanilide (GW9662), a potent antagonist of PPARgamma, and were not mimicked by N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]-l-tyrosine (GW1929), a non-thiazolidinedione PPARgamma agonist. Pioglitazone enhanced aerobic glycolysis and lactate release in astroglia, while the oxidative metabolism of glucose, but not glycolysis, was augmented in neurons without increasing ROS production. These results indicate that pioglitazone may enhance the efficiency of glucose metabolism in the brain.
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An isoindolin-1-one derivate, JM-1232(-), was recently developed as a sedative and hypnotic agent with a strong affinity for the central benzodiazepine binding site of gamma-aminobutyric acid(A) (GABA(A)) receptors. The purpose of this study was to examine the effects of JM-1232(-) on the cardiovascular and sympathetic functions of conscious rats. We investigated the effect of JM-1232(-) on the mean arterial pressure (MAP), heart rate (HR), baroreflex activity, and plasma catecholamine levels in conscious rats. ⋯ A decrease in MAP and an increase in HR induced by JM-1232(-) were antagonized by co-administration of flumazenil. A high dose of JM-1232(-) decreased the plasma norepinephrine concentration, and a subdepressor dose of JM-1232(-) did not affect the baroreceptor reflex. These results show that the i.v. administration of JM-1232(-) decreased MAP mediated by benzodiazepine-GABA(A) receptors.
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The present work investigated the in vitro effects of D-serine (D-Ser) on important parameters of energy metabolism in cerebral cortex of young rats. The parameters analyzed were CO(2) generation from glucose and acetate, glucose uptake and the activities of the respiratory chain complexes I-IV, of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase and of creatine kinase and Na(+),K(+)-ATPase. Our results show that D-Ser significantly reduced CO(2) production from acetate, but not from glucose, reflecting an impairment of the citric acid cycle function. ⋯ We also found that L-serine did not affect citrate synthase activity from mitochondrial preparations and purified enzyme. The data indicate that D-Ser impairs the citric acid cycle activity via citrate synthase inhibition, therefore compromising energy metabolism production in cerebral cortex of young rats. Therefore, it is presumed that this mechanism may be involved at least in part in the neurological damage found in patients affected by disorders in which D-Ser metabolism is impaired, with altered cerebral concentrations of this D-amino acid.