Biomedical Engineering Reference
In-Depth Information
a tight, multilayered, and highly specialized tissue that provides a diffusion barrier,
the perineurium; and, when the nerve trunk comprises more than one fascicle, a
strong sheath that surrounds all fascicles, the epineurium. The permeability barriers
provided by the endoneurium and the perineurium protect the space immediately
outside the nerve fibers from changes in chemical composition, thereby preserving
the electrical conductivity of the fibers. A detailed description of the structure and
function of a nerve trunk is presented in Chap. 5.
Investigators have treated injured peripheral nerves with a variety of agents
that are hypothetical reactants for inducing regeneration. In these studies, outcome
measurements are collected by studying cross sections of regenerated nerves and
typically consist of counts of myelinated and unmyelinated axons, measurements
of the average thickness of the myelin sheath that surrounds an axon, as well as
data on the distribution of axon diameters. This is a decidedly axonocentric view. It
is based on the well-known fact that interruption of axon continuity causes loss of
the ability to conduct electrical signals that nerves uniquely possess. In studies of
peripheral nerve regeneration very little attention has been traditionally paid in the
literature to nonneuronal tissues. Does the large number and important functional
role of axons, not to mention the experimental ease of counting them, merit having
axons be counted as the frequently single, often exclusive, measure of outcome to
be considered in a study of induced nerve regeneration?
Consider the response of axons and Schwann cells in a peripheral nerve follow-
ing two types of injury: a mild injury (crushing of nerve trunk) and a severe injury
(complete cutting of nerve or transection; also referred to as resection or division).
In detailed studies of rat peroneal and sural nerves that had been crushed using
smooth-tipped forceps, observations were made at the crush site and adjacent to
it. It was reported (Haftek and Thomas 1968) that the tubular basement membrane
(
BM tube
) that surrounded a crushed nerve fiber persisted at the crush site; the tube
diameter became shrunken but the tube wall did not rupture. Axon cytoplasm (axo-
plasm), myelin, and Schwann cell cytoplasm inside the BM tubes were all displaced
out of the crushed site. Even though separated by a clear gap at the crush site, the
displaced tissues were retained inside the intact tubes. In the regions adjacent to
the crush site, the BM tubes accommodated this displaced material by becoming
distended but not rupturing. Following release of the crushing force, the shrunk
BM tubes rapidly filled once more at the crush site with the tissues that had been
displaced, and structural recovery across the defect followed (Haftek and Thomas
1968). Not only the axoplasm, but the myelin sheath as well recovered its struc-
ture following a carefully administered crush. By 2 weeks, the myelin sheath had
degenerated to the point where very little myelin could be detected; however, by
4-10 weeks, regeneration of the myelin sheath was complete (Goodrum et al. 1995,
2000). It has been shown that normal function was eventually restored following
mild crushing (Madison et al. 1992). We conclude that, following this mild injury
that severed the axons and induced degeneration of the myelin sheath, but left the
BM tubes intact, axons recovered the continuity of their structure and the nerve
fiber functioned physiologically once more (Fig.
2.3
).
