Facilitating Regrowth of Spinal Cord Cells
By Will Boggs: NEW YORK (Reuters Health) Jul 25 - Chondroitinase fosters the regrowth of neurons through an extracellular matrix bridge implanted at the time of spinal cord injury in adult rats, according to a report in the July 12th issue of The Journal of Neuroscience.
"Regenerating axons can be directed through a bridging graft, towards a specific target in the spinal cord and recovery of behavioral activity can be attributed to the reconnection of these axons across a lesion," Dr. John D. Houle from Drexel University College of Medicine, Philadelphia, told Reuters Health. "Treatment of scar tissue is critical to the success of this approach."
Dr. Houle and colleagues tested the ability of their peripheral nerve graft to bypass a hemisection lesion of the cervical spinal cord of adult rats and to direct regrowing axons to intermediate gray matter distal (below) the level of injury.
"We showed in earlier studies that brain stem neurons retain the ability to regenerate their axon for many months after a spinal cord injury in adult rats, using the peripheral nerve graft model used in this paper," Dr. Houle said.
Axonal growth into the spinal cord often extended for distances beyond 1000 micrometers in animals treated with chondroitinase, the authors report, compared with only 20 to 30 micrometers in untreated animals.
Chondroitinase-treated animals were able to rise up on both forelimbs 3 to 4 weeks after the injury, the results indicate, whereas saline-treated animals were unable to support their weight.
In contrast, animals treated with chondroitinase but without distal graft insertion showed no significant improvement in any task for which they were tested.
"These results demonstrate, for the first time in a model of adult spinal cord injury, the potential to promote extensive axonal regeneration and functional recovery when an autologous nerve graft is combined with modulation of inhibitory extracellular matrix," the authors conclude.
(Autologous- from the same individual, thus avoiding tissue rejection)
"We have completed a study of low and high doses (of chondroitinase]) finding that too much digestion of extracellular matrix compromises the structural arrangement of the injured spinal cord whereas injection of high doses into an intact spinal cord is less harmful," Dr. Houle said. "We have an ongoing study that is examining the possible influence of chondroitinase on invasion by macrophages into tissue that has been treated."
"Because an autologous peripheral nerve graft can be used, and chondroitinase is approved for human use in...the intervertebral disk, it may be possible to advance this combination approach with minimal delay, after demonstration of effectiveness in a larger animal."
J Neurosci 2006;26:7405-7415.