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dc.contributor.authorAlix, James J. P.-
dc.contributor.authorZammit, Christian-
dc.contributor.authorRiddle, Art-
dc.contributor.authorMeshul, Charles K.-
dc.contributor.authorBack, Stephen A.-
dc.contributor.authorValentino, Mario-
dc.contributor.authorFern, Robert-
dc.date.accessioned2018-02-14T08:15:40Z-
dc.date.available2018-02-14T08:15:40Z-
dc.date.issued2012-
dc.identifier.citationAlix, J. J., Zammit, C., Riddle, A., Meshul, C. K., Back, S. A., Valentino, M., & Fern, R. (2012). Central axons preparing to myelinate are highly sensitivity to ischemic injury. Annals of Neurology, 72(6), 936-951.en_GB
dc.identifier.urihttps://www.um.edu.mt/library/oar//handle/123456789/26699-
dc.description.abstractObjective: Developing central white matter is subject to ischemic-type injury during the period that precedes myelination. At this stage in maturation, central axons initiate a program of radial expansion and ion channel redistribution. Here we test the hypothesis that during radial expansion axons display heightened ischemic sensitivity, when clusters of Ca2þ channels decorate future node of Ranvier sites. Methods: Functionality and morphology of central axons and glia were examined during and after a period of modeled ischemia. Pathological changes in axons undergoing radial expansion were probed using electrophysiological, quantitative ultrastructural, and morphometric analysis in neonatal rodent optic nerve and periventricular white matter axons studied under modeled ischemia in vitro or after hypoxia–ischemia in vivo. Results: Acute ischemic injury of central axons undergoing initial radial expansion was mediated by Ca2þ influx through Ca2þ channels expressed in axolemma clusters. This form of injury operated only in this axon population, which was more sensitive to injury than neighboring myelinated axons, smaller axons yet to initiate radial expansion, astrocytes, or oligodendroglia. A pharmacological strategy designed to protect both small and large diameter premyelinated axons proved 100% protective against acute ischemia studied under modeled ischemia in vitro or after hypoxia–ischemia in vivo. Interpretation: Recent clinical data highlight the importance of axon pathology in developing white matter injury. The elevated susceptibility of early maturing axons to ischemic injury described here may significantly contribute to selective white matter pathology and places these axons alongside preoligodendrocytes as a potential primary target of both injury and therapeutics.en_GB
dc.language.isoenen_GB
dc.publisherJohn Wiley & Sons, Inc.en_GB
dc.rightsinfo:eu-repo/semantics/restrictedAccessen_GB
dc.subjectMyelin sheathen_GB
dc.subjectMyelinated neurofibrils -- Diseasesen_GB
dc.subjectCerebral ischemia -- Diagnosisen_GB
dc.subjectAxons -- Physiologyen_GB
dc.titleCentral axons preparing to myelinate are highly sensitivity to ischemic injuryen_GB
dc.typearticleen_GB
dc.rights.holderThe copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holderen_GB
dc.description.reviewedpeer-revieweden_GB
dc.identifier.doi10.1002/ana.23690-
dc.publication.titleAnnals of Neurologyen_GB
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