Journal article
Mechanical membrane injury induces axonal beading through localized activation of calpain
Experimental neurology, v 219(2), pp 553-561
2009
PMID: 19619536
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Diffuse axonal injury (DAI), a major component of traumatic brain injury, is characterized by a sequence of neurochemical reactions initiated at the time of trauma and resulting in axonal degeneration and cell death. Calcium influx through mechanically induced axolemmal pores and subsequent activation of calpains are thought to be responsible for the cytoskeletal damage leading to impaired axonal transport. Focal disruption of cytoskeleton accompanied by the accumulation of transported membranous cargo leads to axonal beading which is the characteristic morphology of DAI. By applying fluid shear stress injury on cultured primary neurons, acute calcium (Ca
2+) and calpain responses of axons to mechanical trauma were investigated. Intracellular Ca
2+ concentration ([Ca
2+]
i) shows a steady increase following injury that can be blocked by sealing membrane pores with Poloxamer 188 and by chelating intra- or extracellular Ca
2+. Calpain activity increases in response to mechanical injury and this increase depends on Ca
2+ availability and on axolemmal permeability. Both the [Ca
2+]
i increase and calpain activity exhibit focal peaks along the axons which co-localize with mitochondria and predict future axonal bead locations. These findings suggest that mechanoporation may be the initiating mechanism resulting in ensuing calcium fluxes and subsequent calpain activity and that post-injury membrane repair may be a valid therapeutic approach for acute intervention in DAI.
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Details
- Title
- Mechanical membrane injury induces axonal beading through localized activation of calpain
- Creators
- Devrim Kilinc - School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Chestnut St., Philadelphia, Pennsylvania 19104, USAGianluca Gallo - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USAKenneth A Barbee - School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Chestnut St., Philadelphia, Pennsylvania 19104, USA
- Publication Details
- Experimental neurology, v 219(2), pp 553-561
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000270157300021
- Scopus ID
- 2-s2.0-69749087083
- Other Identifier
- 991014878229104721
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- Web of Science research areas
- Neurosciences