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Published Online: 20 October 2005

Quantitative Analysis of the Relationship between Intra- Axonal Neurofilament Compaction and Impaired Axonal Transport following Diffuse Traumatic Brain Injury

Publication: Journal of Neurotrauma
Volume 22, Issue Number 10

Abstract

Traumatic axonal injury (TAI) following traumatic brain injury (TBI) contributes to morbidity and mortality. TAI involves intra-axonal changes assumed to progress to impaired axonal transport (IAT), disconnection, and axonal bulb formation. Immunocytochemical studies employing antibodies to amyloid precursor protein (APP), a marker of IAT and RMO14, a marker of neurofilament compaction (NFC), have shown that TAI involves both NFC and IAT, with the suggestion that NFC leads to IAT. Recently, new data has suggested that NFC may occur independently of IAT. The objective of this study was to determine quantitatively the precise relationship between NFC and IAT. Following TBI, rats were studied at 30 min, 3 h, and 24 h. Using single-label immunocytochemistry employing the antibodies RM014, APP, or a combined labeling strategy targeting APP/RMO14 in aggregate, the immunoreactive (IR) profiles were counted in the corticospinal tract (CSpT) and medial lemniscus (ML). In the CSpT, the number of axons demonstrating RMO14-IR approximated the number of axons showing APP-IR, with the APP-IR population showing a significant increase over 24 h (p < 0.05). The sum of both single-label counts equaled the aggregate APP/RMO14 numbers, demonstrating little relationship between NFC and IAT. In the ML, 75% of fibers demonstrated a separation of APP-IR and NFC-IR; however, 25% of the ML fibers showed co-localization of APP-IR and RMO14. The results of these studies indicate that, in the majority of damaged axons, NFC is not associated with IAT. Our findings argue for the use of multiple markers when evaluating the extent of TAI or the efficacy of therapies targeting the treatment of TAI.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 22Issue Number 10October 2005
Pages: 1066 - 1080
PubMed: 16238484

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Published online: 20 October 2005
Published in print: October 2005

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Christina R. Marmarou
Department of Anatomy and Neurobiology, Virginia Commonwealth University Health Center, Virginia Commonwealth University, Richmond, Virginia.
Susan A. Walker
Department of Anatomy and Neurobiology, Virginia Commonwealth University Health Center, Virginia Commonwealth University, Richmond, Virginia.
C. Lynn Davis
Department of Anatomy and Neurobiology, Virginia Commonwealth University Health Center, Virginia Commonwealth University, Richmond, Virginia.
John T. Povlishock
Department of Anatomy and Neurobiology, Virginia Commonwealth University Health Center, Virginia Commonwealth University, Richmond, Virginia.

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