Biomedical Engineering Reference
In-Depth Information
The regenerative effect of an exogenous NGF supply was not confirmed in any
of the following three studies: a 6-week study of two processes of NGF delivery
in the transected mouse sciatic nerve (Santos et al. 1991); a 3-week and a 5-week
study of the transected buccal division of the facial nerve in the rabbit (Spector et al.
1993); and a 10-day study of SC migration as well as a 17-week study of number
of myelinated axons distal to injury in the transected rat sciatic nerve (Bailey et al.
1993). Furthermore, a review of estimated values of the critical axon elongation
(
L
c
) for NGF treatment in Table
6.1
shows no significant increase in
L
c
due to NGF
treatment relative to the untreated control (Hollowell et al. 1990).
Exogenous addition of bFGF enhanced regeneration across gaps (Danielsen
et al. 1988; Aebischer et al. 1989). Alpha-1 acid glycoprotein appeared to lag be-
hind bFGF in regenerative activity (Aebischer et al. 1989). Values of critical axon
elongation in Table
6.1
show a significant shift in critical axon elongation,
ΔL
> 3.3,
following bFGF treatment (Aebischer et al. 1989).
Acidic fibroblast growth factor (aFGF) showed a significant regenerative ac-
tivity in two studies (Cordeiro et al. 1989; Walter et al. 1993) and a very signifi-
cant value of
ΔL
≥ 4.5, confirmed this conclusion (Table
6.1
; Walter et al. 1993).
Treatment with brain-derived neurotrophic factor (BDNF) was reported to have im-
proved recovery of nerve function (Utley et al. 1996). A combination of PDGF-BB
and IGF-I had no effect on PNS regeneration (Wells et al. 1997).
6.4.2
Schwann Cell Addition to the Tubulated Gap
Axons cannot regenerate in the absence of SCs: axon regeneration failed when SCs
were completely prevented from entering a nerve repair site (Hall 1986a, b). How-
ever, SCs do not require axons in order to grow into an injured nerve (Madison and
Archibald 1994). There is evidence that SCs precede axons across the gap of the
nerve tubulation model (Williams et al. 1983; Kljavin and Madison 1991; Son and
Thompson 1995; Fu and Gordon 1997). For these reasons, several investigators
have incorporated SC preparations in the tubulated model of PNS regeneration.
Seeding with SCs has been shown to have had a significant regenerative effect
in three independent studies. The number of myelinated axons in the regenerates
inside SC-seeded tubes was clearly higher than in the unseeded controls (Guénard
et al. 1992; Kim et al. 1994).
Electrophysiological recovery was significantly higher than in controls that
were unseeded with SCs; however, the difference did not emerge until after almost
9 weeks (Kim et al. 1994). By 52 weeks, a regenerate inside a cell-seeded tube
reached a conduction velocity 60 % of normal, a noteworthy result considering that
it had formed across a gap as long as 18 mm in the rat sciatic nerve (Ansselin et al.
1997). Furthermore, a very significant increase in critical axon elongation of SC-
seeded over unseeded experimental groups, amounting to
ΔL
≥ 7.4, was observed
(Table
6.1
).
In contrast to these findings, no difference was detected in the degree of my-
elination or in the electrophysiological behavior between SC-seeded and unseeded
