Spinal Cord Injury
/By Tyler Lanman
Each year, there are approximately 12,000 spinal cord injuries (SCI) in the United States. These devastating injuries occur occur when severe trauma to the spine fractures or dislocates vertebrae, causing the spinal cord to bruise or tear. Spinal cord injuries exhibit a broad range of severity ranging from incomplete to complete. In incomplete SCI, sensation and movement is partially lost below the site of injury. In complete SCI, all sensory and motor functions below the site of injury are completely and permanently lost, resulting in paralysis. The riding accident that resulted in the paralysis of Christopher Reeve is an example of a complete SCI. The location of the SCI also determines the extent of injury. Injuries in the thoracic or lumbar regions can affect the torso, legs, bowel and bladder control, and sexual function. If the injury occurs in the cervical region, the ability to speak, breathe, and use arms can also be impaired. Although there are several treatments available for SCI victims, the damage from injury is largely irreversible.
The damage from SCI occurs in two phases. In the first phase, acute trauma causes primary injury, characterized by severed axon tracts and cell death of neurons. In the second phase, secondary cellular and molecular changes cause edema, necrosis, inflammation, ischemia, and astrogliosis, all of which intensify the damage caused by the primary injury. In astrogliosis, astrocytes, the largest and most abundant glial cells in the central nervous system, undergo morphological and molecular changes such as gap junction establishment and increased synthesis of glial fibrillary acidic protein (GFAP). These astrocytic changes, in turn, result in the formation of a glial scar surrounding the lesion.
The glial scar is both beneficial and detrimental to spinal cord repair after injury. It is favorable in that by isolating the site of injury, inflammation is limited, the blood- brain barrier can be repaired, and tissue damage is reduced. However, the release of several neuro-developmental inhibitor molecules (such as rho and keratan sulphate proteoglycans) from within the glial scar prevent the complete regeneration of the spinal cord and act as a barrier to neuronal axon growth.
As the glial scar is the most important inhibitor factor to neuroregeneration, overcoming this barrier has become a prominent focus of SCI research. One current clinical trial is exploring the drug Cethrin, which inhibits the activation of rho, one of the inhibitory proteins released from the scar. Another trial is investigating ways to promote regeneration by targeting Nogo receptors. In the field of genetics, scientists are currently searching for ways to inhibit histone deacetylases (HDAC), which damage cells via gene expression regulation following SCI. As the glial scar is composed of a tangled group of cells, some researchers are trying to physically break up the tangles, thereby allowing axons to grow past the glial scar. The most promising tangle-clearing drug being investigated is chondroitinase ABC, a bacterial enzyme which has been shown to aid in the functional recovery following SCI.
Although we have made promising advances in the field of spinal cord injuries, a number of significant questions remain unanswered. Hopefully, through the efforts of dedicated basic and clinical researchers, our expanding knowledge of the glial scar will allow us to, one day, develop a tangible treatment that could facilitate the long-distance and functional recovery from spinal cord injuries.
