Biology Reference
In-Depth Information
major functions of neutrophils is to combat pathogens. They may play a role
in remodeling the damaged area to promote wound healing or serve to
recruit monocytes to the injured site. Several interventions that led to
reduction in the number of neutrophils in the injured spinal cord have
been shown to reduce tissue damage and improve functional recovery (
Bao,
Chen, Dekaban, & Weaver, 2004; Bao, Chen, Schneider, & Weaver, 2008;
Gris et al., 2004; Naruo et al., 2003; Taoka et al., 1997
). However, these
effects cannot be attributed only to neutrophils as macrophages are also
affected by these treatments. Nevertheless, as neutrophils release a variety of
proteases and other factors contained in cytoplasmic granules that are
cytotoxic as well as produce free radicals, they are likely to have some
detrimental effect and contribute to secondary damage. However, there is
recent evidence questioning this view (
Stirling, Liu, Kubes, & Yong, 2009
).
The depletion of peripheral macrophages using a systemically adminis-
tered toxin (clodronate) contained in liposomes, which is taken up by mac-
rophages and kills them, was shown to reduce tissue damage at the site of
contusion injury in rats and lead to some improvement in locomotor control
(
Popovich et al., 1999
). In addition, microglia have also been shown to have
cytotoxic properties capable of killing neurons
in vitro
and
in vivo
(
Fordyce,
Jagasia, Zhu, & Schlichter, 2005; Kaushal, Koeberle, Wang, & Schlichter,
2007; Kaushal & Schlichter, 2008
). This cytotoxic effect has been shown to
be mediated by peroxynitrite formation via the generation of superoxide
and nitric oxide. Therefore, activated microglia may also be detrimental in
the injured spinal cord. On the other hand, some studies show that
macrophages have a protective and beneficial effect under certain conditions
after CNS injury. Macrophages recruited to the vitreal space by lens injury
release factors that promote survival of retinal ganglion cells and axon
regeneration after optic nerve injury in rats (
Leon, Yin, Nguyen, Irwin, &
Benowitz, 2000; Yin et al., 2003
). These effects have been reported to be
mediated by a Ca
2
รพ
binding growth factor called oncomodulin (
Yin et al.,
2003, 2006
), as well as by other factors such as ciliary neurotrophic factor
(
Muller, Hauk, & Fischer, 2007
)and
b
and
g
crystallins (
Fischer, Hauk,
Muller, & Thanos, 2008
). In addition, other work has shown that
macrophages activated
in vitro
with segments of peripheral nerve and then
transplanted into different regions of the injured CNS such as the spinal cord
or optic nerve, are protective and promote functional recovery (
Lazarov-
Spiegler, Solomon, & Schwartz, 1998; Lazarov-Spiegler et al., 1996;
Rapalino et al., 1998; Schwartz, Moalem, Leibowitz-Amit, & Cohen, 1999;
Schwartz & Yoles, 2006
). Although there has been much debate in the past
