CELLS OF THE NERVOUS SYSTEM AND ELECTRICAL STIMULATION - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 609

proteins found in the debris inhibit axonal 3 growth (Caroni and Schwab 1988;
Cadelli and Schwab 1991). Since the immune system's intervention is slow in
the CNS—compared to the peripheral nervous system (PNS)—and restricted,
the injury is not properly “cleaned” and healing substances are not delivered.
Furthermore, astrocyte proliferation is activated (Kakulas and Taylor 1992)
producing a physical and chemical (astrocyte secrete soluble factors) barrier,
known as the “glial scar,” through which surviving neurons cannot extend their
axons (Geller and Fawcett 2002). Simply stated, an inhospitable environment
which prevents axonal growth (Houle and Tessler 2003; McKerracher 2001)
emerges and remains after CNS injury.
18.4.1 Repair Strategies
Since the PNS can regenerate when damaged, early attempts to repair the CNS
involved PNS tissue transplants (Horner et al. 2002). In 1980, PNS tissue grafted
into damaged regions of the brain and spinal cord promoted axonal re-growth of
CNS axons (Richardson et al. 1980; Benfey and Aguayo 1982). Grafts composed
of similar tissues, such as fetal spinal cord tissue (Reier et al. 1986), also showed
benefi cial results. Further research made nerve grafts the main approach when
repairing transections of the PNS. However, additional surgery is necessary to
remove donor tissue, and after grafting, total nerve function is not restored.
Therefore, a bioengineered solution that does not depend on donor tissue and
will restore total nerve function is needed in both the CNS and PNS.
Recent approaches to nerve repair investigate chemical, biological, physical,
and electrical stimuli to improve regenerative conditions. Chemical approaches
use pharmacological agents that mimic the action of neurotransmitters and
prevent cell death or interfere with inhibitors of axonal growth (Chierzi and
Fawcett 2001; Rutkowski et al. 2004; McKerracher 2001). Biological strategies
utilize cells that secrete recuperative substances or replace damaged cells alto-
gether (for example, stem cells) (Baizabal et al. 2003; Okano 2002; McDonald
et al. 2004). Physical techniques employ bridges or conduits that link together a
transected nerve (Vroemen et al. 2003; Miller et al. 2002), and/or patterned sur-
faces that guide cells in the proper direction (Recknor et al. 2005). Lastly, electri-
cal, magnetic or electromagnetic stimulation can be applied to injured nerves,
which has been shown to stimulate axonal growth and improve recovery time
(Pfeifer et al. 2004; Mohapel et al. 2004; Sisken 1992; Shapiro et al. 2005).
18.5 ELECTRICAL STIMULATION
The use of electrical stimulation as an investigative or therapeutic tool was not
taken very seriously 100 or so years ago. Most electro-therapeutic treatments
were considered quackery, providing no benefi cial outcome. Shown in Figure
18.3 is an apparatus designed to immerse a patient in an electric fi eld (EF) or
3. Axons are fi brolytic projections that extend from neurons and form connections or synapses with
target cells for communication.