Biomedical Engineering Reference
In-Depth Information
(motor axons) and sensory organs (sensory axons). During development, myelin is
synthesized around axons whose diameter is greater than 0.7 μm, in response to a
signal that includes a diffusible molecule (Garbay et al. 2000); furthermore, myelin
synthesis is upregulated by contact between adjacent SC plasma membranes (Sasa-
gasako et al. 1999). Differentiation of a SC into a myelinating cell requires simulta-
neous interactions with BM and an axon destined for myelination (Fernandez-Valle
et al. 1997). The myelination of SCs following injury is under study (Zhu et al.
2013; Yao et al. 2014).
The myelination of an individual axon is provided along its length by several
SCs. Each cell covers a segment along the axon length (internode); there are points
located between successive SCs that are not covered by myelin (nodes of Ranvier).
Myelination accelerates conduction by preventing propagation of the action poten-
tial along the axon, instead forcing the potential to travel by jumping from node to
node (salutatory conduction). The myelin sheath consists of the plasma membrane
of the SC that is tightly wrapped around the axon perimeter at the internode; these
concentric layers are free of SC cytoplasm. SCs wrapped around an individual axon
are ensheathed in a tubular BM that forms a continuous cover of the myelinated
axon, even at the nodes. During the process of myelination, concentric layers of SC
cytoplasm and plasma membrane envelop the axon; the cytoplasm is then excluded
and the inner surfaces of plasma membrane fuse with each other, providing a multi-
plicity of membrane leaflets that comprise the mature myelin sheath.
The BM surrounding a myelinated axon is very similar to that in skin but is tubu-
lar in shape rather than being primarily a flat surface with indentations (rete ridges),
as in skin. SC BM contains type IV collagen, laminin, type V collagen, entactin,
heparan sulfate proteoglycan, and fibronectin (Bunge and Bunge 1983; McGarvey
et al. 1984; Baron-Van Evercooren et al. 1986; Olsson 1990; Obremski and Bunge
1995). Type IV collagen comprises the fine collagen meshwork that is exclusive to
BMs in various organs. Laminin binds to type IV collagen via entactin; it also binds
to other macromolecular constituents of the BM.
Nonmyelinated axons function in the autonomic nervous system and in small
pain nerves. They comprise fibers of relatively small diameter, typically less than
1 mm. These axons are also surrounded by SCs. Unlike myelinated axons, however,
the supporting SCs have retained their cytoplasm; they ensheathe the axon but are
not wrapped tightly several times around it, and myelin is also absent. Several non-
myelinating axons are frequently surrounded by a single SC (ensheathment) while
the external surface of the latter is encased in a BM (Young et al. 2006). Below we
focus on myelinating axons.
Using standardized nomenclature, we describe a nerve fascicle as being sur-
rounded by a perineurial sheath that forms the border between the endoneurium
inside and the epineurium outside (Olsson 1990). Both myelinated and unmyelin-
ated axons are enclosed in the space inside the fascicle (intrafascicular space) that
is bounded by the perineurial sheath (see below). Nerve fibers are closely surround-
ed by the endoneurial stroma (Fig.
6.2
; top), an extracellular matrix resembling a
fiber-reinforced gel, comprising collagens, fibronectins, proteoglycans, and other
macromolecular components, as well as fibroblasts, macrophages, and mast cells
