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CNS Regeneration (cns + regeneration)
Selected AbstractsNitric oxide regulates axonal regeneration in an insect embryonic CNSDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2008Michael Stern Abstract In higher vertebrates, the central nervous system (CNS) is unable to regenerate after injury, at least partially because of growth-inhibiting factors. Invertebrates lack many of these negative regulators, allowing us to study the positive factors in isolation. One possible molecular player in neuronal regeneration is the nitric oxide (NO),cyclic guanosine-monophosphate (cGMP) transduction pathway which is known to regulate axonal growth and neural migration. Here, we present an experimental model in which we study the effect of NO on CNS regeneration in flat-fillet locust embryo preparations in culture after crushing the connectives between abdominal ganglia. Using whole-mount immunofluorescence, we examine the morphology of identified serotonergic neurons, which send a total of four axons through these connectives. After injury, these axons grow out again and reach the neighboring ganglion within 4 days in culture. We quantify the number of regenerating axons within this period and test the effect of drugs that interfere with NO action. Application of exogenous NO or cGMP promotes axonal regeneration, whereas scavenging NO or inhibition of soluble guanylyl cyclase delays regeneration, an effect that can be rescued by application of external cGMP. NO-induced cGMP immunostaining confirms the serotonergic neurons as direct targets for NO. Putative sources of NO are resolved using the NADPH-diaphorase technique. We conclude that NO/cGMP promotes outgrowth of regenerating axons in an insect embryo, and that such embryo-culture systems are useful tools for studying CNS regeneration. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] Combinatorial treatments for promoting axon regeneration in the CNS: Strategies for overcoming inhibitory signals and activating neurons' intrinsic growth stateDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2007Larry I. Benowitz Abstract In general, neurons in the mature mammalian central nervous system (CNS) are unable to regenerate injured axons, and neurons that remain uninjured are unable to form novel connections that might compensate for ones that have been lost. As a result of this, victims of CNS injury, stroke, or certain neurodegenerative diseases are unable to fully recover sensory, motor, cognitive, or autonomic functions. Regenerative failure is related to a host of inhibitory signals associated with the extracellular environment and with the generally low intrinsic potential of mature CNS neurons to regenerate. Most research to date has focused on extrinsic factors, particularly the identification of inhibitory proteins associated with myelin, the perineuronal net, glial cells, and the scar that forms at an injury site. However, attempts to overcome these inhibitors have resulted in relatively limited amounts of CNS regeneration. Using the optic nerve as a model system, we show that with appropriate stimulation, mature neurons can revert to an active growth state and that when this occurs, the effects of overcoming inhibitory signals are enhanced dramatically. Similar conclusions are emerging from studies in other systems, pointing to a need to consider combinatorial treatments in the clinical setting. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Strategies for identifying genes that play a role in spinal cord regenerationJOURNAL OF ANATOMY, Issue 1 2004M. Wintzer Abstract A search for genes that promote or block CNS regeneration requires numerous approaches; for example, tests can be made on individual candidate molecules. Here, however, we describe methods for comprehensive identification of genes up- and down-regulated in neurons that can and cannot regenerate after injury. One problem concerns identification of low-abundance genes out of the 30 000 or so genes expressed by neurons. Another difficulty is knowing whether a single gene or multiple genes are necessary. When microchips and subtractive differential display are used to identify genes turned on or off, the numbers are still too great to test which molecules are actually important for regeneration. Candidates are genes coding for trophic, inhibitory, receptor and extracellular matrix molecules, as well as unknown genes. A preparation useful for narrowing the search is the neonatal opossum. The spinal cord and optic nerve can regenerate after injury at 9 days but cannot at 12 days after birth. This narrow window allows genes responsible for the turning off of regeneration to be identified. As a next step, sites at which they are expressed (forebrain, midbrain, spinal cord, neurons or glia, intracellular or extracellular) must be determined. An essential step is to characterize proteins, their levels of expression, and their importance for regeneration. Comprehensive searches for molecular mechanisms represent a lengthy series of experiments that could help in devising strategies for repairing injured spinal cord. [source] Multiple sclerosis: a battle between destruction and repairJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Jonathan L. McQualter Abstract Multiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS in which an unrelenting attack from the innate and adaptive arms of the immune system results in extensive demyelination, loss of oligodendrocytes and axonal degeneration. This review summarizes advances in the understanding of the cellular and molecular pathways involved in neurodegeneration following autoimmune-mediated inflammation in the CNS. The mechanisms underlying myelin and axonal destruction and the equally important interaction between degenerative and repair mechanisms are discussed. Recent studies have revealed that the failure of CNS regeneration may be in part a result of the presence of myelin-associated growth inhibitory molecules in MS lesions. Successful therapeutic intervention in MS is likely to require suppression of the inflammatory response, in concert with blockade of growth inhibitory molecules and possibly the mobilization or transplantation of stem cells for regeneration. [source] | ||||||||||