What_Happens_When_The_Spinal_Cord_Is

What Happens When the Spinal Cord Is Injured?

A spinal cord injury usually begins with a sudden, traumatic blow to the spine that fractures or dislocates
vertebrae. The damage begins at the moment of injury when displaced bone fragments, disc material, or
ligaments bruise or tear into spinal cord tissue. Axons are cut off or damaged beyond repair, and neural
cell membranes are broken. Blood vessels may rupture and cause heavy bleeding in the central grey
matter, which can spread to other areas of the spinal cord over the next few hours.

Within minutes, the spinal cord swells to fill the entire cavity of the spinal canal at the injury level. This
swelling cuts off blood flow, which also cuts off oxygen to spinal cord tissue. Blood pressure drops,
sometimes dramatically, as the body loses its ability to self-regulate. As blood pressure lowers even
further, it interferes with the electrical activity of neurons and axons. All these changes can cause a
condition known as spinal shock that can last from several hours to several days.

Although there is some controversy among neurologists about the extent and impact of spinal shock, and
even its definition in terms of physiological characteristics, it appears to occur in approximately half the
cases of spinal cord injury, and it is usually directly related to the size and severity of the injury. During
spinal shock, even undamaged portions of the spinal cord become temporarily disabled and can't
communicate normally with the brain. Complete paralysis may develop, with loss of reflexes and sensation
in the limbs.

The crushing and tearing of axons is just the beginning of the devastation that occurs in the injured spinal
cord and continues for days. The initial physical trauma sets off a cascade of biochemical and cellular
events that kills neurons, strips axons of their myelin insulation, and triggers an inflammatory immune
system response. Days or sometimes even weeks later, after this second wave of damage has passed,
the area of destruction has increased - sometimes to several segments above and below the original
injury - and so has the extent of disability.

Changes in blood flow cause ongoing damage

Changes in blood flow in and around the spinal cord begin at the injured area, spread out to adjacent,
uninjured areas, and then set off problems throughout the body.

Immediately after the injury, there is a major reduction in blood flow to the site, which can last for as long
as 24 hours and becomes progressively worse if untreated. Because of differences in tissue composition,
the impact is greater on the interior grey matter of the spinal cord than on the outlying white matter.

Blood vessels in the grey matter also begin to leak, sometimes as early as 5 minutes after injury. Cells
that line the still-intact blood vessels in the spinal cord begin to swell, for reasons that aren't yet clearly
understood, and this continues to reduce blood flow to the injured area. The combination of leaking,
swelling, and sluggish blood flow prevents the normal delivery of oxygen and nutrients to neurons,
causing many of them to die.

The body continues to regulate blood pressure and heart rate during the first hour to hour-and-a-half
after the injury, but as the reduction in the rate of blood flow becomes more widespread, self-regulation
begins to turn off. Blood pressure and heart rate drop.

Excessive release of neurotransmitters kills nerve cells

After the injury, an excessive release of neurotransmitters (chemicals that allow neurons to signal each
other) can cause additional damage by overexciting nerve cells.

Glutamate is an excitatory neurotransmitter, commonly used by nerve cells in the spinal cord to stimulate
activity in neurons. But when spinal cells are injured, neurons flood the area with glutamate for reasons
that are not yet well understood. Excessive glutamate triggers a destructive process called excitotoxicity,
which disrupts normal processes and kills neurons and other cells called oligodendrocytes that surround
and protect axons.

An invasion of immune system cells creates inflammation
Under normal conditions, the blood-brain barrier (which tightly controls the passage of cells and large
molecules between the circulatory and central nervous systems) keeps immune system cells from entering
the brain or spinal cord. But when the blood-brain barrier is broken by blood vessels bursting and leaking
into spinal cord tissue, immune system cells that normally circulate in the blood - primarily white blood
cells - can invade the surrounding tissue and trigger an inflammatory response. This inflammation is
characterized by fluid accumulation and the influx of immune cells - neutrophils, T-cells, macrophages,
and monocytes.

Neutrophils are the first to enter, within about 12 hours of injury, and they remain for about a day. Three
days after the injury, T-cells arrive. Their function in the injured spinal cord is not clearly understood, but
in the healthy spinal cord they kill infected cells and regulate the immune response. Macrophages and
monocytes enter after the T-cells and scavenge cellular debris.

The up side of this immune system response is that it helps fight infection and cleans up debris. But the
down side is that it sets off the release of cytokines - a group of immune system messenger molecules
that exert a malign influence on the activities of nerve cells.

For example, microglial cells, which normally function as a kind of on-site immune cell in the spinal cord,
begin to respond to signals from these cytokines. They transform into macrophage-like cells, engulf cell
debris, and start to produce their own pro-inflammatory cytokines, which then stimulate and recruit other
microglia to respond.

Injury also stimulates resting astrocytes to express cytokines. These "reactive" astrocytes may ultimately
participate in the formation of scar tissue within the spinal cord.

Whether or not the immune response is protective or destructive is controversial among researchers.
Some speculate that certain types of injury might evoke a protective immune response that actually
reduces the loss of neurons.

Free radicals attack nerve cells
Another consequence of the immune system's entry into the CNS is that inflammation accelerates the
production of highly reactive forms of oxygen molecules called free radicals.

Free radicals then attack and disable molecules that are crucial for cell function - for example, those
found in cell membranes - by modifying their chemical structure. Free radicals can also change how cells
respond to natural growth and survival factors, and turn these protective factors into agents of destruction.

Nerve cells self-destruct

Researchers used to think that the only way in which cells died during spinal cord injury was as a direct
result of trauma. But recent findings have revealed that cells in the injured spinal cord also die from a kind
of programmed cell death called apoptosis, often described as cellular suicide, that happens days or
weeks after the injury.

Apoptosis is a normal cellular event that occurs in a variety of tissues and cellular systems. It helps the
body get rid of old and unhealthy cells by causing them to shrink and implode. Nearby scavenger cells
then gobble up the debris. Apoptosis seems to be regulated by specific molecules that have the ability to
either start or stop the process.

For reasons that are still unclear, spinal cord injury sets off apoptosis, which kills oligodendrocytes in
damaged areas of the spinal cord days to weeks after the injury. The death of oligodendrocytes is
another blow to the damaged spinal cord, since these are the cells that form the myelin that wraps around
axons and speeds the conduction of nerve impulses. Apoptosis strips myelin from intact axons in adjacent
ascending and descending pathways, which further impairs the spinal cord's ability to communicate with
the brain.

Secondary damage takes a cumulative toll

All of these mechanisms of secondary damage - restricted blood flow, excitotoxicity, inflammation, free
radical release, and apoptosis - increase the area of damage in the injured spinal cord. Damaged axons
become dysfunctional, either because they are stripped of their myelin or because they are disconnected
from the brain. Glial cells cluster to form a scar, which creates a barrier to any axons that could potentially
regenerate and reconnect. A few whole axons may remain, but not enough to convey any meaningful
information to the brain.

Researchers are especially interested in studying the mechanisms of this wave of secondary damage
because finding ways to stop it could save axons and reduce disabilities. This could make a big difference
in the potential for recovery.