Zeman Richard J, Wen Xialing, Ouyang Nengtai, Rocchio Ronald, Shih Lynn, Alfieri Alan, Moorthy Chitti, Etlinger Joseph D
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA.
Neurosurgery. 2008 Nov;63(5):981-7; discussion 987-8. doi: 10.1227/01.NEU.0000330404.37092.3E.
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.
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.
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.
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.
目前，由于立体定向放射外科手术的精确性，现在可以通过将辐射束塑形至组织靶点的技术来进行辐射，以用于各种临床应用。这避免了传统照射中对周围组织不必要的、潜在的损伤性照射，从而能够实现对获得最佳治疗效果所需的最小组织体积进行照射。尽管传统的X线照射已被证明可改善动物脊髓损伤后的恢复，但此前尚未证实对损伤脊髓进行靶向照射的疗效。这些研究的目的是确定在标准的脊髓损伤实验模型中，对损伤脊髓进行立体定向X线照射是否能增强运动功能并在挫伤后保留脊髓组织。
使用重物坠落装置在大鼠T10水平造成挫伤损伤，并在损伤后2小时通过Novalis 6兆电子伏直线加速器塑形束放射外科系统（美国BrainLAB公司，伊利诺伊州韦斯特切斯特）以6.4 Gy/分钟的速率分4次连续给予X线照射剂量，束角相隔60至70度。靶体积是沿脊髓轴的一个4×15毫米的圆柱体，等中心位于挫伤中心。损伤后6周用21分的巴索、比蒂和布雷斯纳汉（BBB）运动评分量表测定运动功能，并在脊髓组织学切片中观察组织保留情况。
在损伤后6周的观察期内，运动功能逐渐恢复。与对照组相比，10 Gy X线照射组的BBB评分显著更高（9.4对7.3；P<0.05），表明后肢有负重支撑或背侧迈步，而对照组后肢关节活动但无负重。2至10 Gy范围内的剂量使BBB评分逐渐增加，而15至25 Gy的更高剂量则与较低的BBB评分相关。X线照射治疗后运动恢复的程度与挫伤中心脊髓组织保留的测量结果相关。
这些结果表明立体定向放射外科手术在大鼠急性脊髓挫伤损伤模型中具有有益作用，并为人类治疗策略带来了希望。需要进一步的动物研究来进一步明确潜在益处。
