Biology Reference
In-Depth Information
cord, CD8
þ
and a small number of CD4
þ
T cells are only found months after
injury; B cells however are not detected (
Flemingetal.,2006
).
2.2. Changes in areas undergoing Wallerian degeneration
The inflammatory response at the epicenter of injury results in a rapid and
robust inflammatory response that leads to secondary damage and loss of gray
and white matter. In contrast, the microglial/macrophage response in areas
undergoing Wallerian degeneration in lesioned white matter tracts distal to
the injury is very slow. Wallerian degeneration can take several weeks to
months depending on the region of the CNS affected (
David & Ousman,
2002; George & Griffin, 1994; Stoll, Trapp, & Griffin, 1989
); while in
peripheral nerves, Wallerian degeneration is rapid and occurs within the
first week after injury (
David & Ousman, 2002; Rotshenker, 2011; Stoll,
Griffin, Li, & Trapp, 1989
). The slow time course of Wallerian
degeneration in the CNS is in part due to reduced levels of chemokines
and cytokines as compared to injured peripheral nerves in which this
response is robust (
David & Ousman, 2002; Perrin, Lacroix, Aviles-
Trigueros, & David, 2005; Rotshenker, 2011
). We have shown that
microinjection of MCP-1/MIP-1
a
or IL-1
b
into the dorsal column white
matter 10 mm distal to a dorsal hemisection 5 days after lesion results in
increased recruitment and activation of microglia/macrophages and the
rapid clearance of myelin assessed 9 days later (
Perrin et al., 2005
). These
chemokines and cytokine may therefore play a role in microglia/
macrophage recruitment and activation required for Wallerian degeneration
in white matter tracts. We have also shown that microinjection of
lysophosphatidylcholine (LPC), the hydrolytic product of phospholipase A
2
(PLA
2
), into the spinal cord white matter induces rapid expression within
minutes to hours of MCP-1, MIP-1
a
, GM-CSF, and TNF-
a
that mediate
microglial/macrophage recruitment and activation, and myelin clearance
(
Ousman & David, 2000, 2001
). We will focus our attention in the rest of
this chapter on the inflammatory response at the site of injury and its effects
on secondary damage after SCI.
3. EFFECTS OF IMMUNE CELLS ON SECONDARY
DAMAGE
Neutrophils and microglia/macrophages are the main immune cell
types that respond acutely after SCI. Why neutrophils enter the cord in ster-
ile SCI lesions in experimental animals is not entirely clear as one of the
