Trends in neurosciences
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Chronic pain, whether the result of nerve trauma or persistent inflammation, is a debilitating condition that exerts a high social cost in terms of productivity, economic impact and quality of life. Currently available therapies yield limited success in treating such pain, suggesting the need for new insight into underlying mechanism(s). ⋯ Such activation of descending facilitatory pathways might be the result of neuroplastic changes that occur at medullary sites in response to persistent input of pain signals. Understanding the mechanisms of descending facilitation and the spinal effects of such discharge could provide new insights into the modulation of chronic pain.
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Trends in neurosciences · Oct 2001
ReviewDo active cerebral neurons really use lactate rather than glucose?
Glucose has long been considered the substrate for neuronal energy metabolism in the brain. Recently, an alternative explanation of energy metabolism in the active brain, the astrocyte-neuron lactate shuttle hypothesis, has received attention. It suggests that during neural activity energy needs in glia are met by anaerobic glycolysis, whereas neuronal metabolism is fueled by lactate released from glia. In this article, we critically examine the evidence supporting this hypothesis and explain, from the perspective of enzyme kinetics and substrate availability, why neurons probably use ambient glucose, and not glial-derived lactate, as the major substrate during activity.
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Pain is classically viewed as being mediated solely by neurons, as are other sensory phenomena. The discovery that spinal cord glia (microglia and astrocytes) amplify pain requires a change in this view. ⋯ Similar to spinal infection, these signals cause release of proinflammatory cytokines, thus creating pathological pain. Taken together, these findings suggest a new, dramatically different approach to pain control, as all clinical therapies are focused exclusively on altering neuronal, rather than glial, function.
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Adult oligodendrocyte precursor cells (OPCs) make up around 5-8% of the glial cell population in the CNS. Their function in the undamaged CNS is largely unknown, but their processes are in contact with nodes of Ranvier and synapses, suggesting a regulatory role at these structures. The cells divide slowly, and constitute approximately 70% of cells labelled following a pulse injection of bromodeoxyuridine. ⋯ However, remyelination fails during the later stages of multiple sclerosis, and it is not clear whether this is as a result of a depletion of adult OPCs, inhibition within the glial scar, or damage to the axons that prevents myelination. Adult OPCs are also activated and proliferate following other forms of CNS damage, such as mechanical injury, excitotoxicity and viral infection. The cells produce several of the chondroitin sulphate proteoglycans that might inhibit axon regeneration.
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Brain injury following transient or permanent focal cerebral ischaemia (stroke) develops from a complex series of pathophysiological events that evolve in time and space. In this article, the relevance of excitotoxicity, peri-infarct depolarizations, inflammation and apoptosis to delayed mechanisms of damage within the peri-infarct zone or ischaemic penumbra are discussed. While focusing on potentially new avenues of treatment, the issue of why many clinical stroke trials have so far proved disappointing is addressed. This article provides a framework that can be used to generate testable hypotheses and treatment strategies that are linked to the appearance of specific pathophysiological events within the ischaemic brain.