Final Report Summary - PERICYTESCAR (The role of pericytes in central nervous system scarring and fibrosis)
The healing ability of the central nervous system is very limited and injuries to the brain or spinal cord often result in permanent functional deficits. In many organs, damaged tissue can be repaired by generating new cells of the type that were lost. This does not happen after a lesion in the central nervous system, but scar tissue instead forms at the site of injury. It was recognized more than a century ago that the nerve fibers that conduct signals in the central nervous system, if damaged, fail to grow through the scar tissue that forms at a lesion and reconnect with their targets. The scar tissue has therefore been thought to block nerve fiber regeneration and restoration of function after injuries to the brain and spinal cord. The scar tissue is, however, a complex mesh of different cell types and molecules, and it has been unclear how the scar tissue inhibits nerve fiber regrowth. By studying mice with spinal cord injuries, we have now identified an important mechanism behind this inhibition of nerve fibre regeneration. We found that the explanation lies in a small population of cells lining blood vessels that gives rise to a large part of the scar tissue. Inhibiting scar formation by these blood vessel-associated cells allowed some nerve fibres to grow through the injury and reconnect with other nerve cells. This resulted in improved functional recovery following spinal cord injury in mice. Furthermore, we compared scar formation in the brain and spinal cord and between different lesions, using models of traumatic brain and spinal cord injury, stroke, brain tumor and multiples sclerosis. We found that the same blood vessel lining cells contributed to this specific (fibrotic) scar tissue independent of the lesion cause.
Our findings give an important explanation as to why functional recovery is so limited following injury to the central nervous system and identify a potential target for the treatment of brain and spinal cord lesions.
Further studies are now needed to explore whether this knowledge can be used to promote recovery following injury to the central nervous system in humans.
Our findings give an important explanation as to why functional recovery is so limited following injury to the central nervous system and identify a potential target for the treatment of brain and spinal cord lesions.
Further studies are now needed to explore whether this knowledge can be used to promote recovery following injury to the central nervous system in humans.