Relation entre glucose cérébral et systémique chez le sujet neurolésé: une étude par microdialyse cérébrale

Introduction: Le glucose est le principal substrat énergétique cérébral. Sa concentration dans le cerveau est étroitement liée à la glycémie. Chez le patient neurolésé, du fait de l'augmentation des besoins énergétiques, les réserves cérébrales de glucose sont limitées. Une glycémie suffisamment élevée paraît nécessaire pour assurer un apport adéquat de glucose au cerveau. Objectifs : Le but de cette étude est de mieux comprendre la relation entre glucose cérébral et glycémie lors de lésion cérébrale en analysant la physiologie cérébrale chez des patients neurolésés. Plus précisément nous investiguerons: La relation entre le glucose cérébral et le glucose systémique et son association avec le pronostic vital, l'association entre la neuroglucopénie et différents paramètres cérébraux tel que l'hypertension intracrânienne (HTIC) ou la dysfonction énergétique et finalement l'effet d'une perfusion de glucose 10% sur le glucose cérébral lors d'état de neuroglucopénie. Méthodologie : Analyse d'une base de données prospective comportant des patients souffrant d'un traumatisme crânio-cérébral (TCC) ou une hémorragie sous- arachnoïdienne (HSA) sévères. Les patients comateux sont monitorés par un dispositif intra-parenchymateux avancé, comprenant un cathéter de microdialyse cérébrale et un capteur de PbO2. Résultats : 34 patients consécutifs (moyenne d'âge 42 ans, moyenne de temps jusqu'au début du monitoring : 1.5 jours ± 1 ; moyenne de la durée maximale du monitoring : 6 jours ± 3) ont été étudiés, 25 patients souffrant d'un TCC et 9 patients avec une HSA. Nous avons obtenu une corrélation individuelle entre le glucose cérébral et la glycémie chez 52.9 % des patients. Lorsque la glycémie est inférieure à 5 mmol/l, on observe plus fréquemment des épisodes de neuroglucopénie en comparaison aux valeurs intermédiaires de glycémie (5 - 9.9 mmol/l). Les épisodes d'HTIC (pression intracrânienne (PIC) > 20 mmHg) sont plus fréquemment associés à des épisodes de neuroglucopénie que lorsque la pression intracrânienne est normale 75 % vs. 35%. La dysfonction énergétique est plus souvent associés à des épisodes de neuroglucopénie que lorsque le LPR est normal: 55% contre 36%. Un coefficient de corrélation entre glucose cérébral et glycémie significativement plus élevé a été obtenu chez les survivants que chez les non-survivants (0.1 [interquartile range 0.02- 0.3] contre 0.32 [0.17-0.61]). Chez les patients neuroglucopéniques ayant une corrélation entre glucose cérébral et glycémie, la perfusion de glucose i.v. fait monter le glucose cérébral jusqu'à l'arrêt de la perfusion. Conclusion : Malgré une étroite relation entre glycémie et glucose cérébral en conditions stables, cette relation peut être altérée par des causes cérébrales chez les patients neurolésés montrant que la diminution de la disponibilité du glucose extracellulaire ne résulte pas uniquement d'une hypoglycémie relative mais également de causes cérébrales tel que l'hypoperfusion, l'HTIC ou la dysfonction énergétique.

Holography, thermodynamics and fluctuations of charged AdS black holes

rg model with A3 potential. The holographically dual field theories provide the description of the microscopic degrees of freedom which underlie all of the thermodynamics, as can be seen by examining the form of the microscopic fluctuations.

Induced quantum metric fluctuations and the validity of semiclassical gravity

We propose a criterion for the validity of semiclassical gravity (SCG) which is based on the stability of the solutions of SCG with respect to quantum metric fluctuations. We pay special attention to the two-point quantum correlation functions for the metric perturbations, which contain both intrinsic and induced fluctuations. These fluctuations can be described by the Einstein-Langevin equation obtained in the framework of stochastic gravity. Specifically, the Einstein-Langevin equation yields stochastic correlation functions for the metric perturbations which agree, to leading order in the large N limit, with the quantum correlation functions of the theory of gravity interacting with N matter fields. The homogeneous solutions of the Einstein-Langevin equation are equivalent to the solutions of the perturbed semiclassical equation, which describe the evolution of the expectation value of the quantum metric perturbations. The information on the intrinsic fluctuations, which are connected to the initial fluctuations of the metric perturbations, can also be retrieved entirely from the homogeneous solutions. However, the induced metric fluctuations proportional to the noise kernel can only be obtained from the Einstein-Langevin equation (the inhomogeneous term). These equations exhibit runaway solutions with exponential instabilities. A detailed discussion about different methods to deal with these instabilities is given. We illustrate our criterion by showing explicitly that flat space is stable and a description based on SCG is a valid approximation in that case.

Hydrodynamic fluctuations in fluids under external gradients

Temperature and velocity correlation functions in a fluid subjected to conditions creating both a temperature and a velocity gradient are computed up to second order in the gradients. Temperature and velocity fluctuations are coupled due to convection and viscous heating. When the viscosity goes to infinity one gets the temperature correlation function for a solid under a temperature gradient, which contains a long-ranged contribution, quadratic in the temperature gradient. The velocity correlation function also exhibits long-range behavior. In a particular case its equilibrium term is diagonal whereas the nonequilibrium correction contains nondiagonal terms.

Algebraic decay of velocity fluctuations in a confined fluid

Computer simulations of a colloidal particle suspended in a fluid confined by rigid walls show that, at long times, the velocity correlation function decays with a negative algebraic tail. The exponent depends on the confining geometry, rather than the spatial dimensionality. We can account for the tail by using a simple mode-coupling theory which exploits the fact that the sound wave generated by a moving particle becomes diffusive.

Internal and external fluctuations around nonequilibrium steady states in one-dimensional heat-conduction problems

Thermal fluctuations around inhomogeneous nonequilibrium steady states of one-dimensional rigid heat conductors are analyzed in the framework of generalized fluctuating hydrodynamics. The effect of an external source of noise is also considered. External fluctuations come from temperature and position fluctuations of the source. Contributions of each kind of noise to the temperature correlation function are computed and compared through the study of its asymptotic behavior.

Fluctuations in finite systems: fluctuations in fluids in thermocapillary motion

We compute nonequilibrium correlation functions about the stationary state in which the fluid moves as a consequence of tangential stresses on the liquid surface, related to a varying surface tension (thermocapillary motion). The nature of the stationary state makes it necessary to take into account that the system is finite. We then extend a previous analysis on fluctuations about simple stationary states to include some effects related to the finite size of the sample.

Portal glucose infusion in the mouse induces hypoglycemia: evidence that the hepatoportal glucose sensor stimulates glucose utilization.

To analyze the role of the murine hepatoportal glucose sensor in the control of whole-body glucose metabolism, we infused glucose at a rate corresponding to the endogenous glucose production rate through the portal vein of conscious mice (Po-mice) that were fasted for 6 h. Mice infused with glucose at the same rate through the femoral vein (Fe-mice) and mice infused with a saline solution (Sal-mice) were used as controls. In Po-mice, hypoglycemia progressively developed until glucose levels dropped to a nadir of 2.3 +/- 0.1 mmol/l, whereas in Fe-mice, glycemia rapidly and transiently developed, and glucose levels increased to 7.7 +/- 0.6 mmol/l before progressively returning to fasting glycemic levels. Plasma insulin levels were similar in both Po- and Fe-mice during and at the end of the infusion periods (21.2 +/- 2.2 vs. 25.7 +/- 0.9 microU/ml, respectively, at 180 min of infusion). The whole-body glucose turnover rate was significantly higher in Po-mice than in Fe-mice (45.9 +/- 3.8 vs. 37.7 +/- 2.0 mg x kg(-1) x min)-1), respectively) and in Sal-mice (24.4 +/- 1.8 mg x kg(-1) x min(-1)). Somatostatin co-infusion with glucose in Po-mice prevented hypoglycemia without modifying the plasma insulin profile. Finally, tissue glucose clearance, which was determined after injecting 14C-2-deoxyglucose, increased to a higher level in Po-mice versus Fe-mice in the heart, brown adipose tissue, and the soleus muscle. Our data show that stimulation of the hepatoportal glucose sensor induced hypoglycemia and increased glucose utilization by a combination of insulin-dependent and insulin-independent or -sensitizing mechanisms. Furthermore, activation of the glucose sensor and/or transmission of its signal to target tissues can be blocked by somatostatin.

Spatial analysis of erythrocyte membrane fluctuations by digital holographic microscopy.

Red blood cell (RBC) membrane fluctuations provide important insights into cell states. We present a spatial analysis of red blood cell membrane fluctuations by using digital holographic microscopy (DHM). This interferometric and dye-free technique, possessing nanometric axial and microsecond temporal sensitivities enables to measure cell membrane fluctuations (CMF) on the whole cell surface. DHM acquisition is combined with a model which allows extracting the membrane fluctuation amplitude, while taking into account cell membrane topology. Uneven distribution of CMF amplitudes over the RBC surface is observed, showing maximal values in a ring corresponding to the highest points on the RBC torus as well as in some scattered areas in the inner region of the RBC. CMF amplitudes of 35.9+/-8.9 nm and 4.7+/-0.5 nm (averaged over the cell surface) were determined for normal and ethanol-fixed RBCs, respectively.

Loss of glucose-induced insulin secretion and GLUT2 expression in transplanted beta-cells.

Either 200 or 400 syngeneic islets were transplanted under the kidney capsule of normal or streptozocin-induced diabetic B6/AF1 mice. The diabetic mice with 400 islets became normoglycemic, but those with 200 islets, an insufficient number, were still diabetic after the transplantation (Tx). Two weeks after Tx, GLUT2 expression in the islet grafts was evaluated by immunofluorescence and Western blots, and graft function was examined by perfusion of the graft-bearing kidney. Immunofluorescence for GLUT2 was dramatically reduced in the beta-cells of grafts with 200 islets exposed to hyperglycemia. However, it was plentiful in grafts with 400 islets in a normoglycemic environment. Densitometric analysis of Western blots on graft homogenates demonstrated that GLUT2 protein levels in the islets, when exposed to chronic hyperglycemia for 2 weeks, were decreased to 16% of those of normal recipients. Moreover, these grafts had defective glucose-induced insulin secretion, while the effects of arginine were preserved. We conclude that GLUT2 expression in normal beta-cells is promptly down-regulated during exposure to hyperglycemia and may contribute to the loss of glucose-induced secretion of diabetes.

Food for thought: the importance of glucose and other energy substrates for sustaining brain function under varying levels of activity.

The brain requires a constant and substantial energy supply to maintain its main functions. For decades, it was assumed that glucose was the major if not the only significant source of energy for neurons. This view was supported by the expression of specific facilitative glucose transporters on cerebral blood vessels, as well as neurons. Despite the fact that glucose remains a key energetic substrate for the brain, growing evidence suggests a different scenario. Thus astrocytes, a major type of glial cells that express their own glucose transporter, play a critical role in coupling synaptic activity with glucose utilization. It was shown that glutamatergic activity triggers an enhancement of aerobic glycolysis in this cell type. As a result, lactate is provided to neurons as an additional energy substrate. Indeed, lactate has proven to be a preferential energy substrate for neurons under various conditions. A family of proton-linked carriers known as monocarboxylate transporters has been described and specific members have been found to be expressed by endothelial cells, astrocytes and neurons. Moreover, these transporters are subject to fine regulation of their expression levels and localization, notably in neurons, which suggests that lactate supply could be adjusted as a function of their level of activity. Considering the importance of energetics in the aetiology of several neurodegenerative diseases, a better understanding of its cellular and molecular underpinnings might have important implications for the future development of neuroprotective strategies.

Training in hypoxia fails to further enhance endurance performance and lactate clearance in well-trained men and impairs glucose metabolism during prolonged exercise.

The aim of this study was to investigate the synergistic effects of endurance training and hypoxia on endurance performance in normoxic and hypoxic conditions (approximately 3000 m above sea level) as well as on lactate and glucose metabolism during prolonged exercise. For this purpose, 14 well-trained cyclists performed 12 training sessions in conditions of normobaric hypoxia (HYP group, n = 7) or normoxia (NOR group, n = 7) over 4 weeks. Before and after training, lactate and glucose turnover rates were measured by infusion of exogenous lactate and stable isotope tracers. Endurance performance was assessed during incremental tests performed in normoxia and hypoxia and a 40 km time trial performed in normoxia. After training, performance was similarly and significantly improved in the NOR and HYP groups (training, P < 0.001) in normoxic conditions. No further effect of hypoxic training was found on markers of endurance performance in hypoxia (training x hypoxia interaction, n.s.). In addition, training and hypoxia had no significant effect on lactate turnover rate. In contrast, there was a significant interaction of training and hypoxia (P < 0.05) on glucose metabolism, as follows: plasma insulin and glucose concentrations were significantly increased; glucose metabolic clearance rate was decreased; and the insulin to glucagon ratio was increased after training in the HYP group. In conclusion, our results show that, compared with training in normoxia, training in hypoxia has no further effect on endurance performance in both normoxic and hypoxic conditions or on lactate metabolic clearance rate. Additionally, these findings suggest that training in hypoxia impairs blood glucose regulation in endurance-trained subjects during exercise.

Stimulation of thermogenesis in men after combined glucose-long-chain triglyceride infusion.

The effect of combined long-chain triglyceride infusion (Intralipid 20%) with graded doses of insulin/glucose on energy expenditure was examined in 17 healthy young male volunteers by using the euglycemic insulin clamp technique in combination with indirect calorimetry. Intralipid was infused for 90 min at a constant rate of 0.23 g/min; plasma free fatty acids increased from base-line values of 380 +/- 8 mumol/l to steady state levels of 650 +/- 12 mumol/l. After 90 min the Intralipid was continued and insulin was infused at three rates (0.5, 2, and 4 mU/kg . min) to achieve steady state hyperinsulinemic plateaus of 63 +/- 4, 167 +/- 10, and 410 +/- 15 microU/ml. Plasma glucose concentration was maintained constant at basal euglycemic levels (insulin clamp technique) by infusing glucose at 0.24, 0.48, and 0.59 g/min, respectively. Glucose storage during the insulin clamp (ie, glucose uptake minus glucose oxidation) was 0.13, 0.33, and 0.40 g/min for each group and exogenous lipid storage was 0.17, 0.18, and 0.19 g/min, respectively. The net increment in energy expenditure was 0.15, 0.24, and 0.26 kcal/min, respectively, which represents 8.5% of the energy content of the total amount of glucose and lipid stored. The experimentally determined value (approximately 9%) for the cost of storing both glucose and lipid was found to be significantly greater than predicted by stoichiometric calculations. However, the experimental value for the combined infusion was less than that observed for glucose storage alone (12%). This finding provides support for the use of combined glucose/fat infusions in parenteral nutrition as it is used more economically than when glucose is infused alone.