The Journal of Neuroscience, June 1, 1999, 19(11):4263-4269
High Tolerance and Delayed Elastic Response of Cultured Axons to
Dynamic Stretch Injury
Douglas H.
Smith1,
John
A.
Wolf1,
Theresa A.
Lusardi2,
Virginia M.-Y.
Lee3, and
David F.
Meaney2
Departments of 1 Neurosurgery,
2 Bioengineering, and 3 Pathology and
Laboratory Medicine, University of Pennsylvania, Philadelphia,
Pennsylvania 19104-6316
Although axonal injury is a common feature of brain trauma, little
is known of the immediate morphological responses of individual axons
to mechanical injury. Here, we developed an in vitro
model system that selectively stretches axons bridging two populations of human neurons derived from the cell line N-Tera2. We found that
these axons demonstrated a remarkably high tolerance to dynamic stretch
injury, with no primary axotomy at strains <65%. In addition, the
axolemma remained impermeable to small molecules after injury unless
axotomy had occurred. We also found that injured axons exhibited the
behavior of "delayed elasticity" after injury, going from a
straight orientation before injury to developing an undulating course
as an immediate response to injury, yet gradually recovering their
original orientation. Surprisingly, some portions of the axons were
found to be up to 60% longer immediately after injury. Subsequent to
returning to their original length, injured axons developed swellings
of appearance remarkably similar to that found in brain-injured humans.
These findings may offer insight into mechanical-loading conditions
leading to traumatic axonal injury and into potential mechanisms of
axon reassembly after brain trauma.
Key words:
axon; trauma; elasticity; dynamic deformation; tolerance; axolemmal permeability; neurofilament
Copyright © 1999 Society for Neuroscience 0270-6474/99/19114263-07$05.00/0
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