Stereotactic radiosurgery improves locomotor recovery after spinal cord injury in rats.
OBJECTIVE
Currently, because of the precision of stereotactic radiosurgery, radiation can now be delivered by techniques that shape the radiation beam to the tissue target for a variety of clinical applications. This avoids unnecessary and potentially damaging irradiation of surrounding tissues inherent in conventional irradiation, so that irradiation of the minimum volume of tissue necessary for optimal therapeutic benefit can be achieved. Although conventional x-irradiation has been shown to improve recovery from spinal cord injury in animals, the efficacy of targeted irradiation of the injured spinal cord has not been demonstrated previously. The purpose of these studies was to determine whether stereotactic x-irradiation of the injured spinal cord can enhance locomotor function and spare spinal cord tissue after contusion injury in a standard experimental model of spinal cord injury.


METHODS
Contusion injury was produced in rats at the level of T10 with a weight-drop device, and doses of x-irradiation were delivered 2 hours after injury via a Novalis, 6-MeV linear accelerator shaped beam radiosurgery system (BrainLAB USA, Westchester, IL) in 4 sequential fractions, with beam angles 60 to 70 degrees apart, at a rate of 6.4 Gy/minute. The target volume was a 4 x 15-mm cylinder along the axis of the spinal cord, with the isocenter positioned at the contusion epicenter. Locomotor function was determined for 6 weeks after injury with the 21-point Basso, Beattie, and Bresnahan (BBB) locomotor scale and tissue sparing in histological sections of the spinal cord.


RESULTS
Locomotor function recovered progressively during the 6-week postinjury observation period. BBB scores were significantly greater in the 10-Gy x-irradiated group compared with controls (9.4 versus 7.3; P < 0.05), indicating hind limb weight support or dorsal stepping in contrast to hind limb joint mobility without weight bearing. Doses in the range of 2 to 10 Gy increased BBB scores progressively, whereas greater doses of 15 to 25 Gy were associated with lower BBB scores. The extent of locomotor recovery after treatment with x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter.


CONCLUSIONS
These results suggest a beneficial role for stereotactic radiosurgery in a rat model of acute spinal cord contusion injury and raise hopes for human treatment strategies. Additional animal studies are needed to further define potential benefits.
Zeman
Richard J
RJ
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA. zeman@nymc.edu
Wen
Xialing
X
Ouyang
Nengtai
N
Rocchio
Ronald
R
Shih
Lynn
L
Alfieri
Alan
A
Moorthy
Chitti
C
Etlinger
Joseph D
JD
D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000473:pathology; D016634:Radiosurgery; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000528:radiation effects; D013116:Spinal Cord / Q000473:pathology / Q000528:radiation effects*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D014965:X-Rays