Fractionated radiation facilitates repair and functional motor recovery after spinal cord transection in rat.
Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord.
Kalderon
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N
Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA. kalderon@mskcc.org
Xu
S
S
Koutcher
J A
JA
Fuks
Z
Z
D000818:Animals; D019583:Dose Fractionation, Radiation; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology / Q000528:radiation effects*; D012038:Regeneration / Q000502:physiology / Q000528:radiation effects; D013116:Spinal Cord / Q000502:physiology / Q000528:radiation effects; D013119:Spinal Cord Injuries / Q000532:radiotherapy*; D013904:Thoracic Vertebrae; D014945:Wound Healing / Q000502:physiology / Q000528:radiation effects