| Differential Susceptibility to Axonopathy in Necrotic and Non-Necrotic Perinatal White Matter Injury. | |
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MedLine Citation:
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PMID: 22076007 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: White matter injury (WMI) is the leading cause of brain injury in preterm survivors and results in myelination failure. Although axonal degeneration occurs in necrotic lesions, the role of axonopathy in myelination failure remains controversial for diffuse non-necrotic WMI, which is currently the major form of WMI. We determined the burden of axonopathy in diffuse lesions. METHODS: We analyzed WMI in a preterm fetal sheep model of global cerebral ischemia that replicates the relative burden of necrotic and non-necrotic human WMI. WMI was analyzed at 1 or 2 weeks after ischemia and identified by ex vivo high-field (11.7 Tesla) magnetic resonance imaging of fixed brain tissue. Axonal integrity was analyzed by immunohistochemical detection of axon injury markers and by transmission electron microscopy to quantify axon loss and degeneration in magnetic resonance imaging-defined lesions. RESULTS: Axonal degeneration, defined by staining for neurofilament protein and β-amyloid precursor protein, was restricted to discrete necrotic foci with robust microglial activation. Unexpectedly, axonal degeneration was not visualized in the major form of WMI, which comprised large non-necrotic lesions with diffuse reactive astrogliosis. In these major lesions, quantitative electron microscopy studies confirmed no significant differences in the density of intact and degenerating axons or in the distribution of axon diameters relative to controls. CONCLUSIONS: The mechanism of myelination failure differs significantly in perinatal WMI dependent on the burden of necrosis. Axonopathy is associated with focal necrotic injury but not with primary diffuse non-necrotic lesions, which supports that intact axons in the primary lesions are potential targets for myelination. |
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Authors:
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Art Riddle; Jennifer Maire; Xi Gong; Kevin X Chen; Christopher D Kroenke; A Roger Hohimer; Stephen A Back |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-10 |
Journal Detail:
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Title: Stroke; a journal of cerebral circulation Volume: - ISSN: 1524-4628 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0235266 Medline TA: Stroke Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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From the Departments of Pediatrics, Behavioral Neuroscience, the Advanced Imaging Research Center, the Oregon National Primate Research Center, Obstetrics and Gynecology, and Neurology, Oregon Health & Science University, Portland, Oregon. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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