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S46-1 Neurovascular coupling
29th International Congress of Clinical Neurophysiology analysis are sufficient for nosological diagnosis. Diagnosis of the majority of myopathies, however, still depends on myopathological changes. During the last years, however, molecular testing has significantly broaden the understanding not only of the phenotypical but also of the myopathological variation of classical forms of myopathies. Future chip technology might further reduce the number of myopathies in which biopsy is necessary for diagnosis. S45-4 Periodic paralysis K. Jurkat-Rott1 , F. Lehmann-Horn1 Applied Physiology, Ulm University, Germany
1
Objective: Our goal is to clarify the common pathogenetic mechanism for the episodic and permanent weakness in the primary periodic paralyses (PP). From the pathogenesis, we can deduce therapeutic measures. Methods: We applied patch clamp and voltage clamp in-vitro methods on excised muscle and heterologous expression systems. Additionally, we used our recently developed 23Na-MRI method on patient muscle invivo. Results: Muscle membrane depolarization causes both episodic and permanent weakness. In-vitro, we found a second stable resting potential, P2, whose frequency correlated with muscle force. In-vitro diuretics restored normal resting potential, P1, as well as muscle force. Excised patient muscle suggests that membrane depolarization is caused by a membrane leak. This results in a bi-stability of the resting potential meaning that there are two stable resting potentials, P1 and P2. Any additional slight depolarization of the resting potential will lead to episodic weakness. Such slight depolarizations are caused by both hyperkalemia as well as hypokalemia the mechanisms of which will be explained. Episodic weakness is present when the majority of muscle fibers are at P2. 23Na-MRI shows sodium overload during provoked episodic weakness as a consequence of the depolarizing leak. Diuretically-treated patients show no overload upon provocation corresponding to lack of episodic weakness. In contrast, permanent weakness is caused by only a slight increase in P2 and a loss of bistbaility. 23Na-MRI shows sodium overload at rest without provocation. Diuretically-treated patients with permanent weakness showed reduced overload at rest and varying degree of increase of strength. Conclusions: In PP, weakness is caused by increase of P2. P2 increase is caused by mutation-induced membrane leak combined with depolarizing situations. Restoring of P1 by diuretics restores strength. Early-stage permanent weakness is treatable, especially if 23Na-MRI shows sodium overload. S46. Neuroimaging and electrophysiology S46-1 Neurovascular coupling H. Fukuyama1 Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
1
In 1892, Roy and Sherrington proposed that cerebral blood flow (CBF) changes are associated with neuronal activities based on the various animal experiments. Since then, we believed that in order to observe the neuronal activities, we do the experiments to measure the changes of CBF in the brain. This phenomenon is called as neurovascular coupling. At present, various exceptions have been found in terms of neurovascular tight coupling. For example, misery perfusion syndrome is one of the most famous phenomenons that the brain showed low CBF in spite of high oxygen extraction to preserve the brain function. But we do our functional brain imaging based on Roy and Sherrington hypothesis at this moment. In functional MRI, blood oxygen level dependency (BOLD) is the phenomenon that CBF increase more compared to oxygen metabolism, and T2* images indicated BOLD to increase in the activated area. This phenomenon has been explained by various chemical or physical bases, but still unsettled. The original explanation was that the accumulation of CO2 in the tissue after metabolism increased showed vasodilatation, following CBF increase by CO2 as a strong vasodilator. Recently, various biochemical substances were claimed to increase CBF with increased neuronal activities. Acetylcholine is one of the substances, and NO is another one. These substances are secreted by neurons or endothel of the capillaries. And also direct control of neurons or astrocytes on the vessel walls might be responsible. Other physical factors are operating.
S65 One of them is balloon model that the elastic dilatation and constriction might regulate appropriate CBF perfusion. There are lots of discussions to finalize this important item. S46-2 Neurometabolic coupling M. Lauritzen1 Department of Clinical Neurophysiology, Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark
1
Brain blood flow and oxygen metabolism are vital for normal function in the mammalian nervous system, and provides the basis for normal brain function. The presentation will focus on recent progress in our understanding of how neuronal signalling, and in turn information processing, impacts oxygen metabolism. Evoked activity induces brief and local changes in oxygen metabolism which may be controlled by rapid Ca2+ rises in both pre- and postsynaptic cellular elements, and possibly astrocytes. The high level of energy consumption in the resting state is incompletely understood, but non-signalling house-keeping activities may play a more important role than hitherto believed. All types of nerve cell activities use energy, and during local rises in activity there is a clear correlation between synaptic function and oxygen consumption in most networks. Neurometabolic coupling vary between networks because different synaptic inputs activate different cell types. This points to a complex hierarchical control system of brain energy use. S46-3 Neuron-glia metabolic coupling and plasticity P.J. Magistretti1 1 Ecole Polytechnique Federale de Lausanne, Swiss Federal Institute of Technology Lausanne, Switzerland The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function which has provided the basis for 2-deoxyglucose-based functional imaging with PET. Over the years our group has provided experimental evidence indicating a central role of astrocytes in neurometabolic coupling. Neurometabolic coupling is triggered by the sodium-coupled reuptake by astrocytes of synaptically-released glutamate; the ensuing activation of the Na-K-ATPase triggers glycolysis resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. Analyses of this coupling have been extended in vivo (for review see Magistretti 2006). On the basis of a large body of experimental evidence, we have proposed an operational model ‘the astrocyte-neuron lactate shuttle’. A series of results obtained by independent laboratories has provided further support for this model (For review see Pellerin et al). This body of evidence provides a molecular and cellular basis for interpreting data obtained with functional brain imaging studies (Jolivet et al 2009). This neuron-glia metabolic coupling undergoes plastic in parallel with synaptic plasticity. Thus, specific genes involved in neurometabolic coupling are modulated in the hippocampus during spatial learning. A proinflammatory environment as well as the pathogenic form of beta-amyloid (1 42) modifies the metabolic phenotype of astrocytes, affecting neuronal survival (Allaman et al). Marked variations in the expression of genes in glial glucose and glycogen metabolism are observed during the sleep-wake cycle (Petit et al). Altogether these data suggest that glial metabolic plasticity is likely to be a concomitant of synaptic plasticity. Reference(s) Allaman et al. J Neurosci.; 30:3326 3338 (2010). Magistretti, J Exp. Biol., 209:2304 2311 (2006). Jolivet et al. Front Neuroenergetics 1:4 (2009). Pellerin et al. Glia 55:1251 1262 (2007). Petit et al. (in press, Sleep). S46-4 Membranes, water and diffusion: Potential for brain imaging D. Le Bihan1 1 NeuroSpin, CEA, France Among the astonishing Einstein papers from 1905 there is one which unexpectedly gave birth to a powerful method to explore the brain. Molecular diffusion was explained by Einstein on the basis of the random
1
Objective: Our goal is to clarify the common pathogenetic mechanism for the episodic and permanent weakness in the primary periodic paralyses (PP). From the pathogenesis, we can deduce therapeutic measures. Methods: We applied patch clamp and voltage clamp in-vitro methods on excised muscle and heterologous expression systems. Additionally, we used our recently developed 23Na-MRI method on patient muscle invivo. Results: Muscle membrane depolarization causes both episodic and permanent weakness. In-vitro, we found a second stable resting potential, P2, whose frequency correlated with muscle force. In-vitro diuretics restored normal resting potential, P1, as well as muscle force. Excised patient muscle suggests that membrane depolarization is caused by a membrane leak. This results in a bi-stability of the resting potential meaning that there are two stable resting potentials, P1 and P2. Any additional slight depolarization of the resting potential will lead to episodic weakness. Such slight depolarizations are caused by both hyperkalemia as well as hypokalemia the mechanisms of which will be explained. Episodic weakness is present when the majority of muscle fibers are at P2. 23Na-MRI shows sodium overload during provoked episodic weakness as a consequence of the depolarizing leak. Diuretically-treated patients show no overload upon provocation corresponding to lack of episodic weakness. In contrast, permanent weakness is caused by only a slight increase in P2 and a loss of bistbaility. 23Na-MRI shows sodium overload at rest without provocation. Diuretically-treated patients with permanent weakness showed reduced overload at rest and varying degree of increase of strength. Conclusions: In PP, weakness is caused by increase of P2. P2 increase is caused by mutation-induced membrane leak combined with depolarizing situations. Restoring of P1 by diuretics restores strength. Early-stage permanent weakness is treatable, especially if 23Na-MRI shows sodium overload. S46. Neuroimaging and electrophysiology S46-1 Neurovascular coupling H. Fukuyama1 Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
1
In 1892, Roy and Sherrington proposed that cerebral blood flow (CBF) changes are associated with neuronal activities based on the various animal experiments. Since then, we believed that in order to observe the neuronal activities, we do the experiments to measure the changes of CBF in the brain. This phenomenon is called as neurovascular coupling. At present, various exceptions have been found in terms of neurovascular tight coupling. For example, misery perfusion syndrome is one of the most famous phenomenons that the brain showed low CBF in spite of high oxygen extraction to preserve the brain function. But we do our functional brain imaging based on Roy and Sherrington hypothesis at this moment. In functional MRI, blood oxygen level dependency (BOLD) is the phenomenon that CBF increase more compared to oxygen metabolism, and T2* images indicated BOLD to increase in the activated area. This phenomenon has been explained by various chemical or physical bases, but still unsettled. The original explanation was that the accumulation of CO2 in the tissue after metabolism increased showed vasodilatation, following CBF increase by CO2 as a strong vasodilator. Recently, various biochemical substances were claimed to increase CBF with increased neuronal activities. Acetylcholine is one of the substances, and NO is another one. These substances are secreted by neurons or endothel of the capillaries. And also direct control of neurons or astrocytes on the vessel walls might be responsible. Other physical factors are operating.
S65 One of them is balloon model that the elastic dilatation and constriction might regulate appropriate CBF perfusion. There are lots of discussions to finalize this important item. S46-2 Neurometabolic coupling M. Lauritzen1 Department of Clinical Neurophysiology, Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark
1
Brain blood flow and oxygen metabolism are vital for normal function in the mammalian nervous system, and provides the basis for normal brain function. The presentation will focus on recent progress in our understanding of how neuronal signalling, and in turn information processing, impacts oxygen metabolism. Evoked activity induces brief and local changes in oxygen metabolism which may be controlled by rapid Ca2+ rises in both pre- and postsynaptic cellular elements, and possibly astrocytes. The high level of energy consumption in the resting state is incompletely understood, but non-signalling house-keeping activities may play a more important role than hitherto believed. All types of nerve cell activities use energy, and during local rises in activity there is a clear correlation between synaptic function and oxygen consumption in most networks. Neurometabolic coupling vary between networks because different synaptic inputs activate different cell types. This points to a complex hierarchical control system of brain energy use. S46-3 Neuron-glia metabolic coupling and plasticity P.J. Magistretti1 1 Ecole Polytechnique Federale de Lausanne, Swiss Federal Institute of Technology Lausanne, Switzerland The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function which has provided the basis for 2-deoxyglucose-based functional imaging with PET. Over the years our group has provided experimental evidence indicating a central role of astrocytes in neurometabolic coupling. Neurometabolic coupling is triggered by the sodium-coupled reuptake by astrocytes of synaptically-released glutamate; the ensuing activation of the Na-K-ATPase triggers glycolysis resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. Analyses of this coupling have been extended in vivo (for review see Magistretti 2006). On the basis of a large body of experimental evidence, we have proposed an operational model ‘the astrocyte-neuron lactate shuttle’. A series of results obtained by independent laboratories has provided further support for this model (For review see Pellerin et al). This body of evidence provides a molecular and cellular basis for interpreting data obtained with functional brain imaging studies (Jolivet et al 2009). This neuron-glia metabolic coupling undergoes plastic in parallel with synaptic plasticity. Thus, specific genes involved in neurometabolic coupling are modulated in the hippocampus during spatial learning. A proinflammatory environment as well as the pathogenic form of beta-amyloid (1 42) modifies the metabolic phenotype of astrocytes, affecting neuronal survival (Allaman et al). Marked variations in the expression of genes in glial glucose and glycogen metabolism are observed during the sleep-wake cycle (Petit et al). Altogether these data suggest that glial metabolic plasticity is likely to be a concomitant of synaptic plasticity. Reference(s) Allaman et al. J Neurosci.; 30:3326 3338 (2010). Magistretti, J Exp. Biol., 209:2304 2311 (2006). Jolivet et al. Front Neuroenergetics 1:4 (2009). Pellerin et al. Glia 55:1251 1262 (2007). Petit et al. (in press, Sleep). S46-4 Membranes, water and diffusion: Potential for brain imaging D. Le Bihan1 1 NeuroSpin, CEA, France Among the astonishing Einstein papers from 1905 there is one which unexpectedly gave birth to a powerful method to explore the brain. Molecular diffusion was explained by Einstein on the basis of the random