Biomedical Engineering Reference
In-Depth Information
The tubular configuration as means for reconnecting cut nerves (splicing) has
been extensively used as both a treatment (Weiss 1944; Fields et al. 1989) and an
experimental configuration for containment of test substances (see review by Fu
and Gordon1997). Tubulation profoundly affects the healing response of a transect-
ed nerve, as can be demonstrated by comparing direct healing in the presence and
absence of tubulation (Chamberlain et al. 2000a). For this reason, the tubulated gap
cannot be considered, strictly speaking, a model for study of spontaneous regenera-
tion; instead, it may be looked at as a model for study of induced regeneration. On
the other hand, the difficulties involved in studying transected nerves that have not
been tabulated makes it essential that some tubulation be present during the study.
In this chapter we have adopted a minimally active control, the silicone tube, and
will use that as a baseline to compare the effects of different tubes.
6.1.2
Timescale of Observations: Short-Term and Long-Term
Assays
One of the major differences between studies with skin and peripheral nerve re-
generation is timescale of observation: It is typically reported in days with skin, in
several weeks with nerves. But just how many weeks must elapse for a definitive
measurement? In this section we will attempt to sort through the data in order to
identify a useful timescale range for studies of PNS regeneration. Generally, two
methods have been used to monitor the kinetics of PNS regeneration. In morpho-
logical studies, a histologic tissue section is viewed by microscopy to detect and
count new structures formed. Since each experimental animal usually carries just
one defect, this approach requires a study of many animals before data with statisti-
cal significance can be obtained over any significant time period. In electrophysi-
ological and behavioral studies, however, the same animal is monitored by these
noninvasive studies sequentially through the entire experimental period, yielding
a virtually continuous record of response to the experimental treatment. For this
reason, it is much easier to find in the literature kinetic data in the form of electro-
physiological, rather than morphological, data.
During the first several weeks following surgery, axons in the regenerate elon-
gate across the tubulated gap and new connections in the distal stump are being
made; accordingly, no electrical signal travels along the defect during this “silent”
period, amounting to about 8 weeks for a tubulated 10-mm gap in the rat sciatic
nerve (Chang et al. 1990). The duration of the silent period depends on the gap
length; obviously, morphology becomes the indispensable experimental tool during
this period. The speed of axon elongation across a tubulated gap in the rat sciatic
nerve has been estimated at about 1 mm/day (Williams et al. 1983), sufficient for
bridging of a 10-mm gap in a fraction of the silent period. Obviously, axon elonga-
tion across the gap does not alone suffice to initiate conduction of an electrophysi-
ological signal.
Time constants of regeneration have been extensively studied with electrophysi-
ological procedures. Typical timescales required to reach constant levels (satura-
