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Diffuse Traumatic Injury in the Mouse Disrupts Axon-Myelin Integrity in the Cerebellum
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- Özen, Ilknur (author)
- Lund University,Lunds universitet,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups
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- Arkan, Sertan (author)
- Lund University,Lunds universitet,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups
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- Clausen, Fredrik (author)
- Lund University,Lunds universitet,Laboratory for Experimental Brain Research,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- (creator_code:org_t)
- Mary Ann Liebert Inc, 2022
- 2022
- English 12 s.
- In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 39:5-6, s. 411-422
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Cerebellar dysfunction after traumatic brain injury (TBI) is commonly suspected based on clinical symptoms, although cerebellar pathology has rarely been investigated. To address the hypothesis that the cerebellar axon-myelin unit is altered by diffuse TBI, we used the central fluid percussion injury (cFPI) model in adult mice to create widespread axonal injury by delivering the impact to the forebrain. We specifically focused on changes in myelin components (myelin basic protein [MBP], 2′,3′-cyclic nucleotide 3′-phosphodiesterase [CNPase], nodal/paranodal domains [neurofascin (Nfasc), ankyrin-G], and phosphorylated neurofilaments [SMI-31, SMI-312]) in the cerebellum, remote from the impact, at two, seven, and 30 days post-injury (dpi). When compared with sham-injured controls, cerebellar MBP and CNPase protein levels were decreased at 2 dpi that remained reduced up to 30 dpi. Diffuse TBI induced different effects on neuronal (Nfasc 186, Nfasc 140) and glial (Nfasc 155) neurofascin isoforms that play a key role in the assembly of the nodes of Ranvier. Expression of Nfasc 140 in the cerebellum increased at 7 dpi, in contrast to Nfasc 155 levels, which were decreased. Although neurofascin binding partner ankyrin-G protein levels decreased acutely after cFPI, its expression levels increased at 7 dpi and remained unchanged up to 30 dpi. The TBI-induced reduction in neurofilament phosphorylation (SMI-31) observed in the cerebellum was closely associated with decreased levels of the myelin proteins MBP and CNPase. This is the first evidence of temporal and spatial structural changes in the axon-myelin unit in the cerebellum, remote from the location of the impact site, in a diffuse TBI model in mice.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- cerebellum
- CNPase
- fluid percussion
- myelin
- myelin basic protein (MBP)
- neurofilament
- traumatic brain injury
Publication and Content Type
- art (subject category)
- ref (subject category)
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- Özen, Ilknur
- Arkan, Sertan
- Clausen, Fredrik
- Ruscher, Karsten
- Marklund, Niklas
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- MEDICAL AND HEALTH SCIENCES
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