Brain Trauma - Axonal Shear Injury
Brain Trauma - Axonal Shear Injury
Contrecoup, an injury to the brain often seen in car accidents after high-speed stops, results from the brain bouncing violently against the wall of the skull. This event can cause diffuse axonal injury, also referred to as axonal shearing. This injury involves damage to individual nerve cells (neurons) and loss of connections among neurons which can lead to a breakdown of overall communication among neurons in the brain.
The neuron is the main functional cell of the brain and nervous system, consisting of a cell body (soma), a tail or long nerve fiber (axon), and projections of the cell body called dendrites. The axons travel in tracts or clusters throughout the brain, providing extensive interconnections between brain areas.
Mechanism of Injury
This damage causes a series of reactions that eventually lead to swelling of the axon and disconnection from the cell body of the neuron. In addition, the part of the neuron that communicates with other neurons degenerates and releases toxic levels of chemical messengers called neurotransmitters into the synapse or space between neurons, damaging neighboring neurons through a secondary neuroexcitatory cascade. Therefore, neurons that were unharmed from the primary trauma suffer damage from this secondary insult. Many of these cells cannot survive the toxicity of the chemical onslaught and initiate programmed cell death, or apoptosis. This process usually takes place within the first 24 to 48 hours after the initial injury, but can be prolonged.
One area of research that shows promise is the study of the role of calcium ion influx into the damaged neuron as a cause of cell death and general brain tissue swelling. Calcium enters nerve cells through damaged channels in the axon's membrane. The excess calcium inside the cell causes the axon to swell and also activates chemicals, called proteases, that break down proteins. One family of proteases, the calpains, are especially damaging to nerve cells because they break down proteins that maintain the structure of the axon. Excess calcium within the cell is also destructive to the cell's mitochondria, structures that produce the cell's energy. Mitochondria soak up excess calcium until they swell and stop functioning. If enough mitochondria are damaged, the nerve cell degenerates. Calcium influx has other damaging effects: it activates destructive enzymes, such as caspases that damage the DNA in the cell and trigger programmed cell death, and it damages sodium channels in the cell membrane, allowing sodium ions to flood the cell as well. Sodium influx exacerbates swelling of the cell body and axon.
National Institute of Neurological Disorders and Stroke researchers have shown, in both cell and animal studies, that giving specialized chemicals can reduce cell death caused by calcium ion influx. Other researchers have shown that the use of cyclosporin A, which blocks mitochondrial membrane permeability, protects axons from calcium influx. Another avenue of therapeutic intervention is the use of hypothermia (an induced state of low body temperature) to slow the progression of cell death and axon swelling.
A researcher studies an image generated by an immunofluorescent microscope to understand cell death in the hippocampus, the section of the brain that controls memory. The hippocampus is frequently affected in traumatic brain injury patients. This technology allows the researchers to study what happens to injured cells at the molecular level, and to look for ways to interrupt the chain of chemical events that causes permanent brain damage after a severe head injury.
In the healthy brain, the chemical glutamate functions as a neurotransmitter, but an excess amount of glutamate in the brain causes neurons to quickly overload from too much excitation, releasing toxic chemicals. These substances poison the chemical environment of surrounding cells, initiating degeneration and programmed cell death. Studies have shown that a group of enzymes called matrix metalloproteinases contribute to the toxicity by breaking down proteins that maintain the structure and order of the extracellular environment. Other research shows that glutamate reacts with calcium and sodium ion channels on the cell membrane, leading to an influx of calcium and sodium ions into the cell. Investigators are looking for ways to decrease the toxic effects of glutamate and other excitatory neurotransmitters.
The brain attempts to repair itself after a trauma, and is more successful after mild to moderate injury than after severe injury. Scientists have shown that after diffuse axonal injury neurons can spontaneously adapt and recover by sprouting some of the remaining healthy fibers of the neuron into the spaces once occupied by the degenerated axon. These fibers can develop in such a way that the neuron can resume communication with neighboring neurons. This is a very delicate process and can be disrupted by any of a number of factors, such as neuroexcitation , hypoxia (low oxygen levels), and hypotension (low blood flow). Following trauma, excessive neuroexcitation, that is the electrical activation of nerve cells or fibers, especially disrupts this natural recovery process and can cause sprouting fibers to lose direction and connect with the wrong terminals.
Scientists suspect that these misconnections may contribute to some long-term disabilities, such as pain, spasticity, seizures, and memory problems. NINDS researchers are trying to learn more about the brain's natural recovery process and what factors or triggers control it. They hope that through manipulation of these triggers they can increase repair while decreasing misconnections.
Source: National Institute of Neurological Disorders and Stroke
Last Reviewed: October 2002
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