Department of Medicine & Singapore Institute of Neurotechnology (SINAPSE), National University of Singapore, 28 Medical Dr, 5-COR, Singapore 117456, Singapore.
Department of Medicine & Singapore Institute of Neurotechnology (SINAPSE), National University of Singapore, 28 Medical Dr, 5-COR, Singapore 117456, Singapore; Department of Biomedical Engineering, National University of Singapore, E4, 4 Engineering Dr 3, Singapore 117583, Singapore.
Spine J. 2018 Mar;18(3):507-514. doi: 10.1016/j.spinee.2017.10.066. Epub 2017 Oct 23.
Although general hypothermia is recognized as a clinically applicable neuroprotective intervention, acute moderate local hypothermia post contusive spinal cord injury (SCI) is being considered a more effective approach. Previously, we have investigated the feasibility and safety of inducing prolonged local hypothermia in the central nervous system of a rodent model.
Here, we aimed to verify the efficacy and neuroprotective effects of 5 and 8 hours of local moderate hypothermia (30±0.5°C) induced 2 hours after moderate thoracic contusive SCI in rats.
Rats were induced with moderate SCI (12.5 mm) at its T8 section. Local hypothermia (30±0.5°C) was induced 2 hours after injury induction with an M-shaped copper tube with flow of cold water (12°C), from the T6 to the T10 region. Experiment groups were divided into 5-hour and 8-hour hypothermia treatment groups, respectively, whereas the normothermia control group underwent no hypothermia treatment.
The neuroprotective effects were assessed through objective weekly somatosensory evoked potential (SSEP) and motor behavior (basso, beattie and bresnahan Basso, Beattie and Bresnahan (BBB) scoring) monitoring. Histology on spinal cord was performed until at the end of day 56. All authors declared no conflict of interest. This work was supported by the Singapore Institute for Neurotechnology Seed Fund (R-175-000-121-733), National University of Singapore, Ministry of Education, Tier 1 (R-172-000-414-112.).
Our results show significant SSEP amplitudes recovery in local hypothermia groups starting from day 14 post-injury onward for the 8-hour treatment group, which persisted up to days 28 and 42, whereas the 5-hour group showed significant improvement only at day 42. The functional improvement plateaued after day 42 as compared with control group of SCI with normothermia. This was supported by both 5-hour and 8-hour improvement in locomotion as measured by BBB scores. Local hypothermia also observed insignificant changes in its SSEP latency, as compared with the control. In addition, 5- and 8-hour hypothermia rats' spinal cord showed higher percentage of parenchyma preservation.
Early local moderate hypothermia can be induced for extended periods of time post SCI in the rodent model. Such intervention improves functional electrophysiological outcome and motor behavior recovery for a long time, lasting until 8 weeks.
虽然全身低温已被确认为一种具有临床应用价值的神经保护干预手段，但急性中度局部低温在创伤性脊髓损伤（SCI）后的应用正被认为是一种更有效的方法。此前，我们已经研究了在啮齿动物模型中诱导中枢神经系统长时间局部低温的可行性和安全性。
本研究旨在验证在大鼠中度胸段创伤性 SCI 后 2 小时诱导 5 小时和 8 小时局部中度低温（30±0.5°C）的疗效和神经保护作用。
大鼠在 T8 节段诱导中度 SCI（12.5mm）。伤后 2 小时，使用带有冷水（12°C）的 M 形铜管诱导局部低温（30±0.5°C），从 T6 到 T10 区域。实验分组为 5 小时和 8 小时低温治疗组，而正常体温对照组不进行低温治疗。
通过每周客观体感诱发电位（SSEP）和运动行为（Basso、Beattie 和 Bresnahan 评分）监测评估神经保护作用。在第 56 天结束时进行脊髓组织学检查。所有作者均声明无利益冲突。这项工作得到了新加坡神经技术种子基金（R-175-000-121-733）、新加坡国立大学、教育部 Tier 1（R-172-000-414-112）的支持。
我们的结果显示，8 小时治疗组从损伤后第 14 天开始，SSEP 幅度开始明显恢复，持续至第 28 天和第 42 天，而 5 小时组仅在第 42 天显示出明显改善。与体温正常的 SCI 对照组相比，运动功能在第 42 天后达到平台期。这得到了 5 小时和 8 小时 BBB 评分改善的支持。局部低温也观察到 SSEP 潜伏期没有明显变化，与对照组相比。此外，5 小时和 8 小时低温组大鼠脊髓的实质保存率更高。
在啮齿动物模型中，SCI 后可长时间诱导早期局部中度低温。这种干预可改善长时间的功能电生理结果和运动行为恢复，持续至 8 周。
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