Cell elimination as a strategy for repair in acute spinal cord injury.
Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later stages of wound healing (the third week after injury) triggering chronic inflammation and progressive tissue decay that is the characteristic pathology of spinal cord injury. Specific cell elimination within a critical time window after injury can lead to repair in the acutely injured spinal cord. Cell proliferation events can be manipulated/modified by x-irradiation. Clinically, numerous radiation protocols (i.e., radiation therapy) have been developed that specifically eliminate the rapidly dividing cells without causing any noticeable/significant damage to the tissue as a whole. Radiation therapy when applied within the critical time window after injury prevents the onset of chronic inflammation thus leading to repair of structure and function. Various aspects of the development of this cell-elimination strategy for repair in acute spinal cord injury by utilizing radiation therapy are being reviewed. Topics reviewed here: identifying the window of opportunity; and the beneficial repair effects of radiation therapy in a transection injury model and in a model relevant to human injury, the contusion injury model. The possible involvement of cellular components of the blood-spinal cord barrier as the trigger of chronic inflammation and/or target of the radiation therapy is discussed.
Kalderon
Nurit
N
Sloan-Kettering Institute for Cancer Research, Box 280, 1275 York Avenue, New York, NY 10021, USA. kalderon@mskcc.org
D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects*; D006801:Humans; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology / Q000532:radiotherapy*