Radiation Therapy Combined With Microsurgery Shows Promise For Curing Injured Spinal Cord

Currently there is no cure for human spinal cord injury. Treatment after injury is largely limited to steroids administered to prevent further deterioration. "This research opens the door to developing a clinical protocol for curing human spinal cord injuries using conventional therapies," said lead researcher Nurit Kalderon, Ph.D. Conducted at Sloan-Kettering Institute for Cancer Research in New York City, the research was supported by a grant from the National Institute of Neurological Disorders and Stroke (NINDS).

The hallmark of spinal cord injury is progressive tissue decay at the damage size. Kalderon's previous research indicated that the spinal cord is able to repair itself in the early days after injury but is thwarted in its efforts during the second or third week by certain cells that block the repair process.

In earlier research on rats with cords that were completely severed, Kalderon was able to show that radiation therapy, similar to that used in cancer treatment, given localized at the lesion site during the third week following injury helped the spinal cord heal itself by eliminating the cells that interfere with its natural repair processes. The research established a connection between the body's ability to repair the wounded cord and recovery of motor function. Once the wound was healed, the severed brain-cord fibers could grow across the lesion site, restoring the connection between the brain and the spinal cord, with resulting restoration of control of the brain over muscle function.

In the current research, the scientists made a severe crush injury, similar to a human contusion/fracture injury, in spinal cord of adult rats just below the waist. In crush injuries, tissue decay is exacerbated by the secondary damage caused by massive swelling as fluids build up from the injured blood vessels. When the researchers administered radiation alone, there was no detectable beneficial effect on the body's repair of the crushed cord. However, the researchers recalled findings from nearly a century ago by Alfred R. Allen showing that incision at the damage site along the midline of the cord (myelotomy) could drain the accumulated fluids and reduce tissue damage.

Kalderon and her colleagues at Sloan-Kettering then made longitudinal micro-incisions down the center of the injured cord within the first 24 hours after injury to release the fluid buildup. There was significant reduction in the size of lesion site, confirming Allen's work. They then combined the radiation treatment with the microsurgery. When a midline incision was performed at one hour after injury, followed by localized radiation therapy given for ten days starting on day ten after injury, there was nearly a two-fold improvement in the body's ability to heal the injured cord compared with untreated rats. This suggests that fluid accumulation and swelling must first be prevented if the radiation therapy is to be effective in promoting wound repair.

The researchers were able to show the improvements in wound healing both by post-mortem examination of the tissue three months after injury, as well as MRI on the living rats. This indicates that the success of these therapies on humans could also be evaluated using MRI technology.

The researchers also tested a third level of treatment. Recognizing that exercise may increase tissue repair, they added ten minutes of treadmill exercise five days a week to the radiation therapy, starting at the second week after injury. Again, the spinal cord ability to repair itself was markedly improved. Rats treated with incisions to reduce the harmful fluid accumulation, followed by radiation therapy at the site to remove damaging cells and regular treadmill exercise saw a three-fold improvement in the body's ability to repair the severely crushed cord, going from 19% of cord tissue that was healthy in untreated rats to 56.3% of cord tissue that was repaired and saved from further damage.

"This research provides hope for spinal cord injury victims that paralysis can indeed be prevented or repaired with a combination of conventional therapies at the time of injury," according to Kalderon.

The research was conducted at Sloan-Kettering Institute by Nurit Kalderon, Manickam Muruganandham, Jason A. Koutcher and Melissa Potuzac. Kalderon is currently with the Spinal Cord Injury Repair Laboratory in New York City, Muruganandham is with the University of Iowa Hospitals and Clinics, and Potuzak is with the University of Pennsylvania. "Therapeutic Strategy for Acute Spinal Cord Contusion Injury: Cell Elimination Combined with Microsurgical Intervention," was published July 18, 2007 in PLoS One. (http://www.plosone.org/doi/pone.0000565)

Citation: Kalderon N, Muruganandham M, Koutcher JA, Potuzak M (2007) Therapeutic Strategy for Acute Spinal Cord Contusion Injury: Cell Elimination Combined with Microsurgical Intervention. PLoS One 2(7): e565. doi:10.1371/journal.pone.0000565