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Evolution of Axonal Injury in the Closed Head Impact Model of Engineered Rotational Acceleration in Adult Ferrets

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dc.contributor.authorKrieg, J.L.
dc.contributor.authorAntolis, K.
dc.contributor.authorHooper, C.
dc.contributor.authorKapuwelle, H.
dc.contributor.authorGeorge, R.
dc.contributor.authorO'Brien, W.T.
dc.contributor.authorMcDonald, S.J.
dc.contributor.authorLeonard, A.V.
dc.contributor.authorTurner, R.J.
dc.contributor.authorCorrigan, F.
dc.date.issued2025
dc.description.abstractConcussion-related symptoms, such as impaired balance, slower processing speed, attention deficits, memory dysfunction, and irritability, are thought to result from diffuse axonal injury (DAI), characterized by selective damage to white matter axons. Axons subjected to this mechanical stretch injury exhibit diverse pathological changes, including disruption of axonal transport, neurofilament compaction and degradation, myelin sheath disruption, and loss of sodium channels required for action potential generation and propagation. These distinct forms of axonal pathology may evolve differentially over time and preferentially localize to specific white matter tracts. In this study, we employed the clinically relevant ferret model of concussion using the closed head impact model of engineered rotational acceleration (CHIMERA). 55 male ferrets were randomly allocated to sham or injury groups and then to either 24 h, 72 h, or 14d survival time points. We confirmed that axonal transport disruption and neurofilament pathology represent independent processes, with minimal colocalization but a shared peak of around 72 h following injury. Furthermore, we observed a persistent loss of ankyrin-G, a critical anchoring protein for sodium channels at the node of Ranvier, up to 14d postinjury, suggesting that the resultant impairment in axonal transmission may underlie many concussion symptoms. Indeed, injured ferrets displayed significant deficits in balance, working memory, spatial memory, and recognition memory. These findings demonstrate that the CHIMERA model in ferrets recapitulates key axonal pathologies and their associated clinical manifestations following concussion. This model offers a valuable platform for investigating the temporal evolution of axonal injury and developing targeted therapeutic interventions to mitigate concussion-related deficits.
dc.description.statementofresponsibilityJustin L. Krieg, Kosta Antolis, Carl Hooper, Hasini Kapuwelle, Rebecca George, William T. O'Brien, Stuart J. McDonald, Anna V. Leonard, Renée J. Turner, Frances Corrigan
dc.identifier.citationJournal of Neuroscience Research, 2025; 103(11):e70090-1-e70090-22
dc.identifier.doi10.1002/jnr.70090
dc.identifier.issn0360-4012
dc.identifier.issn1097-4547
dc.identifier.orcidKrieg, J.L. [0000-0001-6813-2147]
dc.identifier.orcidGeorge, R. [0000-0003-3625-3598]
dc.identifier.orcidLeonard, A.V. [0000-0002-9430-3314]
dc.identifier.orcidTurner, R.J. [0000-0003-4278-8302]
dc.identifier.orcidCorrigan, F. [0000-0001-6150-8893]
dc.identifier.urihttps://hdl.handle.net/2440/148167
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1145183
dc.rights© 2025 Wiley Periodicals LLC.
dc.source.urihttps://doi.org/10.1002/jnr.70090
dc.subjectaxonal injury; cognition; diffuse traumatic brain injury; ferret; motor; myelin; oligodendrocytes
dc.subject.meshAxons
dc.subject.meshAnimals
dc.subject.meshFerrets
dc.subject.meshBrain Concussion
dc.subject.meshDiffuse Axonal Injury
dc.subject.meshHead Injuries, Closed
dc.subject.meshDisease Models, Animal
dc.subject.meshAxonal Transport
dc.subject.meshAcceleration
dc.subject.meshRotation
dc.subject.meshMale
dc.titleEvolution of Axonal Injury in the Closed Head Impact Model of Engineered Rotational Acceleration in Adult Ferrets
dc.typeJournal article
pubs.publication-statusPublished

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