Biology Reference
In-Depth Information
Absence or delay of this resolution phase results in chronic inflammation.
We will first present a brief overview of the cellular changes in the immune
response after SCI. This will be followed by a discussion of our recent studies
on the identification and characterization of several molecules that regulate
inflammation and mediate secondary damage after SCI.
2. THE INFLAMMATORY RESPONSE AFTER SCI
2.1. Changes at the site of injury
The cells that respond most rapidly to SCI are those within the CNS itself.
In situ
hybridization and immunohistochemical analysis of cytokine expression
in tissue sections indicate that in addition to microglia (the resident tissue mac-
rophage in the CNS), other cells including astrocytes, neurons, and oligoden-
drocytes rapidly express proinflammatory cytokines that can influence the
recruitment and activation of peripheral immune cells into the injured spinal
cord. For example, IL-1
b
mRNA expression peaks at 12 h after SCI in mice
and is expressed mainly by microglia and astrocytes (
Pineau & Lacroix, 2007
).
A similar rapid expression of IL-1
b
is also detected in injured rat and human
spinal cord at the protein level using immunostaining of tissue sections (
Yang
et al., 2004, 2005
). Interestingly, in humans, IL-1
b
is detected in neurons at
30 min and in neurons and microglia at 5 h after injury (
Yang et al., 2004
).
TNF-
a
mRNA expression after SCI in mice peaks at 1 h and decreases by
24 h, followed by a second prominent peak between 14 and 28 days
(
Pineau & Lacroix, 2007
). At the early time-points (1-3 h), TNF-
a
mRNA is expressed by all CNS cell types—microglia, astrocytes, neurons,
and oligodendrocytes (
Pineau & Lacroix, 2007
), and at later times
(2 weeks), it is expressed mainly by activated microglia/macrophages
(
Pineau & Lacroix, 2007
). In the injured human spinal cord, TNF-
a
is detected at 1-3 h at the protein level in neurons and in cells with a
microglial morphology (
Yang et al., 2005
). A number of chemokines
(macrophage inflammatory protein-1
a
and
b
[MIP-1
a
and MIP-1
b
], MIP-2,
monocyte chemotactic protein-1 [MCP-1] and interferon-inducible protein
10 [IP10/CXCL10]) are also upregulated within 30 min after SCI and peak
at 6 h (
Rice, Larsen, Rivest, & Yong, 2007
). Similar changes are also seen in
other CNS conditions such as brain ischemia with some differences. For
example, IL-1
b
mRNA and protein are upregulated between 15 and
30 min postischemia and have a biphasic behavior with a second peak
between 6 and 24 h after ischemia/reperfusion. TNF-
a
mRNA expression
