Biology Reference
In-Depth Information
According to the localization of the lesion, until recently, most peripheral
nerve regeneration studies had beenmainly carried out on the rat sciatic nerve
model, primarily because it is the largest peripheral nerve (
Baptista et al.,
2007; Luis et al., 2007; Varejao et al., 2004
). However, since most of the
human peripheral nerve injuries affect the upper extremity, the necessity
of an experimentalmodel closer to clinical interests is required. Indeed, recent
years have shown an increasing interest toward the employment of major
forelimb nerves (
Geuna et al., 2007; Papalia, Tos, Scevola, Raimondo, &
Geuna, 2006; Papalia, Tos, Stagno d'Alcontres, Battiston, & Geuna, 2003;
Sinis et al., 2008; Tos et al., 2009
). In particular, the median nerve attracted
the attention of peripheral nerve researchers because of the availability of an
easier and more reliable behavioral test (the grasping test) (
Lee, Tos, et al.,
2007; Papalia et al., 2003; Tos et al., 2007
).
According to the type of lesion, so far, two main experimental lesion par-
adigms have been adopted for nerve regeneration studies: (1) axonotmesis
(crush), which is characterized by complete interruption of nerve fibers con-
tinuity without discontinuing the nerve, and (2) neurotmesis, which is a com-
plete transection of the whole nerve. The complete nerve transection requires
surgical repair to reestablish epineurial continuity. This experimental paradigm
provides not only the model for the comparative investigation of new types of
microsurgical and tissue engineering approaches for nerve reconstruction but
also a good model for assessing the effectiveness of various postoperative treat-
ments (drugs, physical therapy, diet, etc.). On the other hand, with a crush
lesion, the injured axons are provided with an optimal regeneration pathway,
represented by the nerve segment distal to the injury, without the need for the
microsurgical repair. This experimental approach is therefore less technically
challenging and is particularly suitable when a reproducible regeneration
process is required, such as for the study of the biological mechanisms of
regeneration or rationale development for new therapeutic agents.
Recent advances in molecular neurobiology include the development of
transgenic mice that have been used in multiple areas, including the field
of developmental neurobiology and disease processes such as cancer and
diabetes, but their use has extended also to the study of peripheral nerve
regeneration subsequent to traumatic injuries.
In particular, knockout mice, which carry a targeted gene inactivated
through genetic engineering, are useful to elucidate the role of a particular
gene or protein in a physiologic pathway by evaluating the consequences of
its inactivation. On the other hand, transgenic animals that overexpress a
particular gene or proteins are available, thus circumventing methodological
