Biology Reference
In-Depth Information
1. INTRODUCTION
The adult mammalian central nervous system (CNS) has a very limited
capacity to regenerate damaged axons through the CNS environment, and
to replace damaged neurons. As a result, injuries to the spinal cord result in
permanent loss of motor, sensory, and autonomic function. Damage to
CNS tissue after spinal cord injury (SCI) occurs in two phases—the acute phase
in which damage is caused as a direct result of the trauma itself, and a subacute
phase in which secondary damage to CNS tissue occurs due to a variety of
factors that include ischemia, hemorrhage, excitotoxic damage, and inflamma-
tion. The inflammatory response is thought to contribute importantly to sec-
ondary damage after SCI, and is mainly an innate immune response, involving
infiltrating macrophages and neutrophils, and CNS-resident microglia.
In experimental models of SCI, the size of the lesion increases over time,
particularly over the first 2 weeks. Degenerative changes involving atrophy
and loss of neurons and myelin also occur over a more prolonged course of
several months that have been shown to be mediated in part by the adaptive
immune response involving lymphocytes and antibody production (
Ankeny
& Popovich, 2009
). Therapeutic strategies to promote axon regeneration
(discussed in other chapters) to reconnect severed fiber pathways either by
long distance axon growth (
David & Lacroix, 2003
) or short distance relays
(
Courtine et al., 2008; van den Brand et al., 2012
) are required to restore
motor and sensory function after SCI. However, the degree to which axon
regeneration is required may be substantially reduced by minimizing the
secondary damage to fiber tracts. Much attention has therefore been
focused over the past decade in understanding the mechanisms underlying
secondary damage. Here, we will focus our attention on one aspect that
mediates secondary damage, namely, the role of inflammation.
Cell and tissue damages that are caused by inflammation is generally a
bystander effect of inflammation, the primary role of which is to control
infections, clear cellular debris, and promote wound healing. Inflammation
therefore plays an important and useful role. The aim in SCI would there-
fore be to curb certain harmful aspects of the inflammatory response while
still allowing its useful beneficial effects in wound healing and tissue repair.
In addition, inflammation in its natural course gets resolved and switched off.
The resolution of inflammation is a combination of downregulation of
proinflammatory molecules and the expression of proresolution factors that
actively suppress inflammation (
Serhan, Chiang, & Van Dyke, 2008
).
