The central nervous system unique characteristics
contribute to its trauma response. This begins with the blood brain barrier
that excludes serum proteins from the extracellular area. The blood brain
barrier is a physical metabolic barrier formed of capillary endothelial cells
that restrict the movement of serum proteins and small polar molecules between
the blood and the brain fluid. The purpose of this is to prevent a higher
degree of damage to the brain by allowing the brain a controlled amount of
vascular derived fluid to the brain to prevent swelling. Microglia which are the macrophages of the
CNS, are in a resting state and need to be activated in order to get a response.
Spinal cord injury according to Hausmann (2003), induces synthesis of
tenascin-C, keratin sulphate and chondroitin sulphate proteoglycans (CSPs) by
reactive microglia, macrophages, oligodendrocytes which are insulators for axons
in the central nervous system (Answers.com, 2009). This is caused from the
acute inflammatory response that is due to the spinal cord injury in the
central nervous system.
The inflammatory response from trauma is greater in
the spinal cord than the cerebral cortex. This is seen by a lessened response
of the neutrophils and activated macrophage and extent of infiltration in the
cerebral cortex than the spinal cord. The initial damage of the spinal cord is
due to the contusion and within the first few hours, the lesion is far greater
than the initial injury. This correlates to the functional outcome and is
called a secondary injury.
The primary injury to the spinal cord is typically
from the trauma that causes necrosis and bleeding. The progression the
surrounding tissue is known as secondary injury. The three areas of secondary
response from spinal cord injury are vascular, biochemical and cellular. In the
vascular response, the blood spinal-cord barrier triggers inflammation response
by invasion of neutrophils and macrophages. Endothelial and glial cells release
vasoactive substances like bradykinins, histamines and nitric oxide which
influence the perfusion and crossing of plasma-derived molecules of the spinal
cord. This extends along the axis of the injured spinal cord and not limited to
the
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injured site. The
spinal cord is more permeable than the brain following a comparable injury. This
event lasts maximum of one day, and then gradually declines. Tator &
Koyanagi (2007), report that in spinal cord injury haemorrhagic patterns were
more pronounced in the grey matter of the brain tissue. Conversely, most of the
white matter showed nonhaemorrhagic degenerative changes including myelin
degradation changes and axonal swelling in the acute stage. The authors suggest
that since none of the major arteries on the surface of the spinal cord were
found to be occluded, the intramedullary vascular system may be primarily
responsible for the vascular damage. Ischemic tissue exhibits a loss of
adenosine triphosphate (ATP), or energy. The restoration of ATP pools in some
cells causing reperfusion injury because of the inability to reoxygenate. This
leads to energy-dependant apoptosis, or cell death (Hausmann, 2003).
Biochemical events of secondary injury include
glutamate which is an excitatory neurotransmitter that after its release
transmitter proteins remove glutamate from the extracellular area. This is what happens under normal
circumstances to prevent glutamate accumulation. Although, when spinal cord injury occurs,
elevations of extracellular glutamate concentrations rise to neurotoxic levels.
Glial and neuronal glutamate transmitter proteins elevate six hours after
spinal cord injury and decreasing over the next 24 hours. Hypoxia makes cells
more sensitive to high levels of glutamate. The overload of cellular calcium or
CA+2 is closely related to glutamate induced traumatic and ischemic
neuronal cell death (Webelements, 2009). Activation of cellular death is caused
by the activated glutamate by N-methyl-D-aspartate receptors. This causes
cellular CA+2 into the neurons which in turn lead to cell death.
Free radicals are formed in small amounts from the mitochondrial electron chain
transport system. They are also formed
in larger amounts as a consequence on insufficient oxygen or trauma injuries.
These free radicals can damage proteins, nucleic acids and lipids. Free
radicals are unstable organic molecules that cause the body to age through
tissue damage and disease. Nitrite oxide
is a gas produced in small amounts in the central nervous system by the
vascular endothelium and neurons. Between days 1-12 post trauma, NO is found in
large amounts causing significant neuronal and locomotor dysfunction. This
excessive NO is thought to be the cause of neurotoxicity along with free
radicals (Hausmann, 2003).
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Secondary
tissue loss in the central nervous system causes a loss of energy substrates
like mitochondria. Mitochondria are the energy producing structures within
cells. The mitochondria electron chain transport system uses simple sugar and
oxygen to create adenosine triphosphate (ATP), the energy mitochondria can use.
They serve as energy buffers during physiological and pathological conditions
and are damaged in the event of mechanical or ischemic injury. This is likely due to the CA+2 overload
that then damage the mitochondria and the ATP which causes the cell to die
(McCance & Huether, 2006).
The
cellular reaction to secondary injury of spinal cord injury begins with the
first inflammatory cells to arrive which are the neutrophils. The job of the
neutrophils is to remove tissue debris and return the body back to homeostasis
(Neutropena Association Inc., 2008). The amount of neutrophils is elevated by
the third hour up until the third day post trauma and is measured by the amount
of myeloperoxidase activity which becomes elevated at those times. Neutrophils
release proteases and reactive oxygen enzymes and elastase which are enzymes
that may damage endothelial cells causing higher vascular permeability. The
consequence of these enzymes may cause hemorrhage as a result of neutrophils elastase
endothelial damage (Sommers & Johnson, 2002).
Microglia occupies 13% of the glial cell population
and responds through morphology from disturbances within their environment. Microglia
are macrophages from bone marrow that when activated from antigenic
stimulation, travel to the injured site within the central nervous system (ALS
Forum, 2006). Microglia release
cytokines as leucotrienes and prostaglandins, the reason for this is probably
rapid phagocytosis of debris and thus control the inflammatory response at the
lesion site (Lilley and Aucker, 2005). Cytokines as leucotrienes and
prostaglandins that help to regulate the body’s immune system by producing the
necessary chemicals needed to fight infection (Wisegeek, 2009). The number of
microglia increase the first 7 days post trauma then plateaus around 2-4 weeks.
If the activated microglia prolong their release of inflammatory cytokines in
the central nervous system, then they may cause further destruction, however,
activated microglia generate growth factors needed for neuronal survival and
tissue repair. The environment controls the microglia response (Sommers &
Johnson, 2002).
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