Vipin Ashwati, Kortelainen Jukka, Al-Nashash Hasan, Chua Soo Min, Thow Xinyuan, Manivannan Janani, Thakor Nitish V, Kerr Candace L, All Angelo H
1 Singapore Institute for Neurotechnology, National University of Singapore , Singapore, Singapore .
2 Biomedical Engineering Research Group, Department of Computer Science and Engineering, University of Oulu , Oulu, Finland .
Ther Hypothermia Temp Manag. 2015 Sep;5(3):152-62. doi: 10.1089/ther.2015.0005. Epub 2015 Jun 9.
Hypothermia is known to be neuroprotective and is one of the most effective and promising first-line treatments for central nervous system (CNS) trauma. At present, induction of local hypothermia, as opposed to general hypothermia, is more desired because of its ease of application and safety; fewer side effects and an absence of severe complications have been noted. Local hypothermia involves temperature reduction of a small and specific segment of the spinal cord. Our group has previously shown the neuroprotective effect of short-term, acute moderate general hypothermia through improvements in electrophysiological and motor behavioral assessments, as well as histological examination following contusive spinal cord injury (SCI) in rats. We have also shown the benefit of using short-term local hypothermia versus short-term general hypothermia post-acute SCI. The overall neuroprotective benefit of hypothermia can be categorized into three main components: (1) induction modality, general versus local, (2) invasive, semi-invasive or noninvasive, and (3) duration of hypothermia induction. In this study, a series of experiments were designed to investigate the feasibility, long-term safety, as well as eventual complications and side effects of prolonged, semi-invasive, moderate local hypothermia (30°C±0.5°C for 5 and 8 hours) in rats with uninjured spinal cord while maintaining their core temperature at 37°C±0.5°C. The weekly somatosensory evoked potential and motor behavioral (Basso, Beattie and Bresnahan) assessments of rats that underwent 5 and 8 hours of semi-invasive local hypothermia, which revealed no statistically significant changes in electrical conductivity and behavioral outcomes. In addition, 4 weeks after local hypothermia induction, histological examination showed no anatomical damages or morphological changes in their spinal cord structure and parenchyma. We concluded that this method of prolonged local hypothermia is feasible, safe, and has the potential for clinical translation.
低温已知具有神经保护作用，是中枢神经系统（CNS）创伤最有效且最具前景的一线治疗方法之一。目前，与全身低温相比，诱导局部低温更受青睐，因为其应用简便且安全；已注意到副作用较少且无严重并发症。局部低温涉及脊髓一小段特定区域的温度降低。我们的团队此前已通过改善电生理和运动行为评估以及大鼠脊髓挫伤性损伤（SCI）后的组织学检查，证明了短期、急性中度全身低温的神经保护作用。我们还展示了急性SCI后使用短期局部低温与短期全身低温相比的益处。低温的总体神经保护益处可分为三个主要方面：（1）诱导方式，全身与局部，（2）侵入性、半侵入性或非侵入性，以及（3）低温诱导持续时间。在本研究中，设计了一系列实验来研究在未受伤脊髓的大鼠中进行长时间、半侵入性、中度局部低温（30°C±0.5°C，持续5小时和8小时）同时将其核心体温维持在37°C±0.5°C的可行性、长期安全性以及最终的并发症和副作用。对接受5小时和8小时半侵入性局部低温的大鼠进行每周体感诱发电位和运动行为（Basso、Beattie和Bresnahan）评估，结果显示电导率和行为结果无统计学显著变化。此外，局部低温诱导4周后，组织学检查显示其脊髓结构和实质无解剖损伤或形态变化。我们得出结论，这种长时间局部低温方法是可行、安全的，并且具有临床转化潜力。
