Borgens R B, Toombs J P, Breur G, Widmer W R, Waters D, Harbath A M, March P, Adams L G
Department of Basic Medical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907, USA.
J Neurotrauma. 1999 Jul;16(7):639-57. doi: 10.1089/neu.1999.16.639.
We show that an applied electric field in which the polarity is reversed every 15 minutes can improve the outcome from severe, acute spinal cord injury in dogs. This study utilized naturally injured, neurologically complete paraplegic dogs as a model for human spinal cord injury. The recovery of paraplegic dogs treated with oscillating electric field stimulation (OFS) (approximately 500 to 600 microV/mm; n = 20) was compared with that of sham-treated animals (n = 14). Active and sham stimulators were fabricated in West Lafayette, Indiana. They were coded, randomized, sterilized, and packaged in Warsaw, Indiana, and returned to Purdue University for blinded surgical implantation. The stimulators were of a previously unpublished design and meet the requirements for phase I human clinical testing. All dogs were treated within 18 days of the onset of paraplegia. During the experimental applications, all received the highest standard of conventional management, including surgical decompression, spinal stabilization (if required), and acute administration of methylprednisolone sodium succinate. A radiologic and neurologic examination was performed on every dog entering the study, the latter consisting of standard reflex testing, urologic tests, urodynamic testing, tests for deep and superficial pain appreciation, proprioceptive placing of the hind limbs, ambulation, and evoked potential testing. Dogs were evaluated before and after surgery and at 6 weeks and 6 months after surgery. A greater proportion of experimentally treated dogs than of sham-treated animals showed improvement in every category of functional evaluation at both the 6-week and 6-month recheck, with no reverse trend. Statistical significance was not reached in comparisons of some individual categories of functional evaluation between sham-treated and OFS-treated dogs (ambulation, proprioceptive placing); an early trend towards significance was shown in others (deep pain), and significance was reached in evaluations of superficial pain appreciation. An average of all individual scores for all categories of blinded behavioral evaluation (combined neurologic score) was used to compare group outcomes. At the 6-month recheck period, the combined neurologic score of OFS-treated dogs was significantly better than that of control dogs (p = 0.047; Mann-Whitney, two-tailed).
我们发现,每15分钟反转一次极性的外加电场能够改善犬类严重急性脊髓损伤的预后。本研究采用自然损伤、神经学上完全性截瘫的犬类作为人类脊髓损伤的模型。将接受振荡电场刺激(OFS)(约500至600微伏/毫米;n = 20)治疗的截瘫犬的恢复情况与假手术治疗动物(n = 14)进行比较。有源和假刺激器在印第安纳州西拉斐特制造。它们经过编码、随机分组、消毒,并在印第安纳州华沙包装,然后返回普渡大学进行盲法手术植入。这些刺激器采用了此前未发表的设计,符合I期人体临床试验的要求。所有犬在截瘫发作后18天内接受治疗。在实验应用期间,所有犬都接受了最高标准的常规治疗,包括手术减压、脊柱稳定(如有需要)以及急性给予琥珀酸钠甲泼尼龙。对每只进入研究的犬进行了放射学和神经学检查,后者包括标准反射测试、泌尿系统测试、尿动力学测试、深浅痛觉测试、后肢本体感觉放置、行走和诱发电位测试。在手术前后以及术后6周和6个月对犬进行评估。在6周和6个月的复查中,与假手术治疗动物相比,接受实验治疗的犬在功能评估的各个类别中表现出改善的比例更高,且没有逆转趋势。在假手术治疗犬和OFS治疗犬之间的某些个体功能评估类别(行走、本体感觉放置)比较中未达到统计学显著性;在其他类别(深部疼痛)中显示出早期的显著性趋势,而在浅部痛觉评估中达到了显著性。使用所有类别盲法行为评估的所有个体评分的平均值(综合神经学评分)来比较组间结果。在6个月的复查期,OFS治疗犬的综合神经学评分显著优于对照犬(p = 0.047;曼-惠特尼检验,双侧)。