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Glial Cells: The “Dark Matter” of the Brian

By the time a patient gets to the emergency room, unconscious from a trauma, the primary injury to the brain – that is the structural damage to the brain tissue, neurons and blood vessels of the brain has already occurred. However, we know that this acute injury also sets into motions a complex cascade of molecular events known to create “secondary damage” to the brain. While this very complex puzzle has not been completely unraveled, we do know that one of the chemical events that occur after trauma to the brain is “oxidative stress”. The human body generally stays in balance by producing reactive oxygen species (ROS) and using them as part of our immune system. These molecules are highly reactive and destructive and are essential for keeping our immune system intact. However, after a trauma the balance is thrown out of whack and far too many ROS molecules are thrown into the blood stream. This condition of oxidating stress is also thought to be important in many neuro-regenerative diseases such as Lou Gehrig’s disease, Parkinson’s, Huntington’s Disease and Alzheimers. Key structures of the brain in all of this are the glial cells, a long ignored part of our brains.

In the early 1900’s there was a battle that raged over the make-up of the human brain between brilliant Spanish scientist Raymond Cajal and Italian Camillo Golgi. Cajal proposed that brain function was a rising from neurons in the brain, which was correct, but his theory reduced another important part of the brain structure, the glial cells, to an insignificant structural role only. However, in the past fifteen years it has been discovered that the glial cells are active in the brain and involved in many parts of cognition and memory. This is exciting because the glial cells make up a huge part of the brain structure and are currently almost like the “dark matter” of the universe. They are there but no one pays attention to them and no one knows all of what they do quite yet. There are several type of glial cells present in the human nervous system:

  • Astrocytes – These cells outnumber neurons five to one and are also found in the brain capillaries that form the “blood/brain barrier” that restricts what substances and molecules can enter the brain. The BBB, as it is called, is very important in regards to a traumatic brain injury. It is thought that one of the injuries in trauma is a tearing or weakening of the BBB. Once that occurs the destructive ROS type molecules that the BBB generally keeps away from the brain are let in. This causes inflammation and destruction of brain tissue. It is thought that epilepsy can arise from a tear in the BBB as well as Alzheimer’s and other neuro-degenerative diseases. Every month brings more research about additional functions of astrocytes in the brain.
  • Microglia – These are small cells that remove waste from central nervous system cells and offer protection as part of the immune system.
  • Oligodendrocytes – These are central nervous system structures that wrap around axons (the telegraph wire long branch of a neuron) and its insulating coat known as the myelin sheath. The destruction of this material can occur in high speed accidents or blast injuries. When the axons are stretched the coating can fall off or be damaged. This disables or adversely affects the neuron because of its electrical signal is then impaired. The new technology of MR/DTI can visualize this type of injury in the white matter of the human brain very sensitively. Water molecules that are suppose to run along the inside of the myelin in a straight line are shown on MR/DTI to be moving almost randomly in all directions. This is how damage is visualized on an MR/DTI.
  • Schwann Cells – These cells are also involved in the myelin sheath of a neuron and assist in the conduction of impulses.

A Study published in January 2010, in Nature showed that astrocytes, which comprise 90% of all human brain cells, are indeed involved in the electrical process that constitute thinking. The astrocyte needs to give a burst of electricity during the process, and thus is intimately related with neurons and the creation of cognition, contrary to 60 years of prior wisdom.

Not until the glial system further studies will we know enough about the chemical cascade following traumatic brain injury to prevent it. Current animal studies have shown great promise as an anti-oxidative neuro-protective medicine for the compound edaravone (Wang GH, et al., 2011) which has been shown to inhibit oxidative stress and inflammatory response as well as reducing glial activation. These compounds will not be available, unfortunately, for several years.