Spinal Cord Injury: Treatments and Rehabilitation (cont.)
Jason C. Eck, DO, MS
Dr. Eck received a Bachelor of Science degree from the Catholic University of America in Biomedical Engineering, followed by a Master of Science degree in Biomedical Engineering from Marquette University. Following this he worked as a research engineer conducting spine biomechanics research. He then attended medical school at University of Health Sciences. He is board eligible in orthopaedic surgery.
In this Article
- Spinal Cord Injury Facts
- What is the spinal cord injury?
- What are the causes of spinal cord injury?
- What are the symptoms of spinal cord injury?
- How is a spinal cord injury diagnosed?
- How is a spinal cord injury treated?
- What is the outlook for patients with spinal cord injury?
- Is there a cure for spinal cord injury?
- Where can I get more information on spinal cord injury?
- NIH spinal cord injury: treatments and rehabilitation
- What is a spinal cord injury?
- How does the spinal cord work?
- What happens when the spinal cord is injured?
- What are the immediate treatments for spinal cord injury?
- How does a spinal cord injury affect the rest of the body?
- How does rehabilitation help people recover from spinal cord injuries?
- How is research helping spinal cord injury patients?
- The future of spinal cord research
- Find a local Doctor in your town
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 are produced as a by-product of normal cell metabolism. In the healthy spinal cord their numbers are small enough that they cause no harm. But injury to the spinal cord, and the subsequent wave of inflammation that sweeps through spinal cord tissue, signals particular cells to overproduce 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.
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