Spinal Cord Injury/Repair It has been estimated that in the US alone there are 200,000 individuals with spinal cord injuries. While the lifetime costs of care have been estimated to be as high as $9 billion, the impact on individuals and their families cannot be estimated in dollars. Despite the critical need for treatments to encourage recovery of function, the spinal cord typically undergoes very little functional recovery.

The Injury Cascade Spinal cord injury occurs in two phases; first a primary compression of the tissue which damages cells, membranes and blood vessels. Within four hours, there is myelin sheath disruption, neuronal and vascular injury. A secondary injury cascade follows in which ischemia, hypoxia and free radical release produce inflammation, membrane damage and neuronal cell death.

The Problem: cross sections of damaged cord For functional recovery, there must be survival of neurons, axonal regeneration, synapse formation and re-myelination. Despite the dogma that the CNS cannot regenerate, it has been known since the last century that when CNS neurons are transplanted into peripheral nerve, they survive. Similarly, when a section of peripheral nerve is transplanted into damaged cord, CNS neurons will survive and grow through the nerve. These observations suggest that neurons have the ability to regenerate into the proper environment

Why can the PNS regenerate and the CNS cannot? When a peripheral nerve is injured, it undergoes an initial phase of “Wallerian degeneration” in which the axon degenerates, followed by a period of re-growth. The regenerating axon follows the path of the basement membrane of the Schwann cells which previously supported it, to accurately find its old target. Oligos in the CNS behave very differently than Schwann cells. Not only do they not have a basement membrane, they express proteins which inhibit axon re-growth.

In addition to inhibitory molecules produced by oligodendrocytes, astrocytes present at the injury divide and hypertrophy, a condition known as reactive gliosis. This “glial scar” forms a physical barrier to regeneration. Two examples of reactive astrocytes (silver stain)

Cell transplants can recolonize damaged tissue and bridge the gap One ideal source of cells for transplantation into the injured cord is the embryonic stem (ES) cell. Because they come from the early blastocyst, ES cells proliferate extensively, can be induced to differentiate into both neurons and glial cells, and can be transduced to express required growth factors. In this study, ES cells were implanted into the damaged CNS, and after 16 weeks, the grafted cells had integrated, restored function, and expressed appropriate neurotransmitters (white letters are abbreviations). www.pnas.org/cgi/doi/10.1073/pnas.022438099

Other Therapeutic Targets In addition to ES cell transplants to aid recovery, other scientists are using antibodies to the inhibitory substance produced by the oligodendrocytes to promote recovery. Others are working to inhibit the cell division and hypertrophy of the astrocytes. There have been very few clinical trials of these approaches, although scientists in Sweden have implanted neural stem cells into brains of Parkinsons patients, and neurosurgeons in the US have implanted cells from a tumor cell line into brain of stroke victims. These approaches are a beginning for what will likely evolve into standard therapies.