Journal article
Mechanically-induced membrane poration causes axonal beading and localized cytoskeletal damage
Experimental neurology, v 212(2), pp 422-430
2008
PMID: 18572167
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Diffuse axonal injury (DAI), a major component of traumatic brain injury, is a manifestation of microstructural cellular trauma and various ensuing neurochemical reactions that leads to secondary neuronal death. DAI is suggested to result from the initial increase in the membrane permeability caused by the mechanical forces acting on the axons. Permeability increases disturb ion balance and lead to cytoskeletal disruption resulting in the impairment of axonal transport. We present an
in vitro model that reproduces important features of
in vivo DAI such as membrane permeability changes, focal disruption of microtubules, impaired axonal transport, and focal accumulation of organelles. We induced fluid shear stress injury (FSSI) on cultured primary chick forebrain neurons and characterized the resulting structural and morphological changes. In addition, we tested the effect of Poloxamer 188 (P188), a tri-block co-polymer that is known to promote resealing membrane pores. We found that FSSI induces mechanoporation that leads to axonal bead formation, the “hallmark” morphology of DAI. Beads contained accumulated mitochondria and co-localized with focal microtubule disruptions, also a characteristic of DAI. Post-injury P188 treatment prevented FSSI-induced membrane permeability changes and reduced axonal beading to control levels. These results indicate that acute mechanoporation of axons in response to injury is a necessary condition for subsequent axonal pathology, suggesting that membrane integrity is a potential target for therapeutic interventions. P188 provides neuroprotection via resealing the plasma membrane following injury and prevents focal disruption of microtubules and axonal bead formation.
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Details
- Title
- Mechanically-induced membrane poration causes axonal beading and localized cytoskeletal damage
- Creators
- Devrim Kilinc - School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Chestnut Street, 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 Street, Philadelphia, Pennsylvania 19104, USA
- Publication Details
- Experimental neurology, v 212(2), pp 422-430
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000258252000025
- Scopus ID
- 2-s2.0-47349091839
- Other Identifier
- 991014877716004721
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- Web of Science research areas
- Neurosciences