Journal article
Partial interruption of axonal transport due to microtubule breakage accounts for the formation of periodic varicosities after traumatic axonal injury
Experimental neurology, v 233(1), pp 364-372
Jan 2012
PMID: 22079153
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Abstract
Due to their viscoelastic nature, white matter axons are susceptible to damage by high strain rates produced during traumatic brain injury (TBI). Indeed, diffuse axonal injury (DAI) is one of the most common features of TBI, characterized by the hallmark pathological profiles of axonal bulbs at disconnected terminal ends of axons and periodic swellings along axons, known as “varicosities.” Although transport interruption underlies axonal bulb formation, it is unclear how varicosities arise, with multiple sites accumulating transported materials along one axon. Recently, axonal microtubules have been found to physically break during dynamic stretch injury of cortical axons in vitro. Here, the same in vitro model was used in parallel with histopathological analyses of human brains acquired acutely following TBI to examine the potential role of mechanical microtubule damage in varicosity formation post-trauma. Transmission electron microscopy (TEM) following in vitro stretch injury revealed periodic breaks of individual microtubules along axons that regionally corresponded with undulations in axon morphology. However, typically less than a third of microtubules were broken in any region of an axon. Within hours, these sites of microtubule breaks evolved into periodic swellings. This suggests axonal transport may be halted along one broken microtubule, yet can proceed through the same region via other intact microtubules. Similar axonal undulations and varicosities were observed following TBI in humans, suggesting primary microtubule failure may also be a feature of DAI. These data indicate a novel mechanism of mechanical microtubule damage leading to partial transport interruption and varicosity formation in traumatic axonal injury.
► Diffuse axonal injury results in transport interruption observed as varicosities along axons. ► Using a model of axonal stretch injury the mechanism of axonal varicosity formation was examined. ► Individual microtubule breakage results in partial transport interruption and varicose swelling. ► Similar varicosities found in humans indicate primary microtubule failure may be a feature of DAI.
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Details
- Title
- Partial interruption of axonal transport due to microtubule breakage accounts for the formation of periodic varicosities after traumatic axonal injury
- Creators
- Min D Tang-Schomer - Penn Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USAVictoria E Johnson - Penn Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USAPeter W Baas - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19104, USAWilliam Stewart - Division of Clinical Neurosciences, University of Glasgow, Glasgow, UKDouglas H Smith - Penn Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA
- Publication Details
- Experimental neurology, v 233(1), pp 364-372
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000300123900041
- Scopus ID
- 2-s2.0-84856216795
- Other Identifier
- 991014878148104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences