title: Prolonged Local Hypothermia Has No Long-Term Adverse Effect on the Spinal Cord.
abstract: 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.
authors.affiliation: 1 Singapore Institute for Neurotechnology, National University of Singapore , Singapore, Singapore .
authors.forename: Ashwati
authors.initials: A
authors.lastname: Vipin
authors.affiliation: 2 Biomedical Engineering Research Group, Department of Computer Science and Engineering, University of Oulu , Oulu, Finland .
authors.forename: Jukka
authors.initials: J
authors.lastname: Kortelainen
authors.affiliation: 3 Department of Electrical Engineering, American University of Sharjah , Sharjah, United Arab Emirates .
authors.forename: Hasan
authors.initials: H
authors.lastname: Al-Nashash
authors.affiliation: 1 Singapore Institute for Neurotechnology, National University of Singapore , Singapore, Singapore .
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Chua
authors.affiliation: 1 Singapore Institute for Neurotechnology, National University of Singapore , Singapore, Singapore .
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Thow
authors.affiliation: 4 Department of Orthopedic Surgery, National University of Singapore , Singapore, Singapore .
authors.forename: Janani
authors.initials: J
authors.lastname: Manivannan
authors.affiliation: 1 Singapore Institute for Neurotechnology, National University of Singapore , Singapore, Singapore .
authors.lastname: Astrid
authors.affiliation: 1 Singapore Institute for Neurotechnology, National University of Singapore , Singapore, Singapore .|5 Department of Biomedical Engineering, Johns Hopkins School of Medicine , Baltimore, Maryland.
authors.forename: Nitish V
authors.initials: NV
authors.lastname: Thakor
authors.affiliation: 6 Department of Biochemistry and Molecular Biology, University of Maryland , Baltimore, Maryland.
authors.forename: Candace L
authors.initials: CL
authors.lastname: Kerr
authors.affiliation: 1 Singapore Institute for Neurotechnology, National University of Singapore , Singapore, Singapore .|4 Department of Orthopedic Surgery, National University of Singapore , Singapore, Singapore .|5 Department of Biomedical Engineering, Johns Hopkins School of Medicine , Baltimore, Maryland.|7 Department of Biomedical Engineering, National University of Singapore , Singapore, Singapore .|8 Division of Neurology, Department of Medicine, National University of Singapore , Singapore, Singapore .|9 Department of Neurology, Johns Hopkins School of Medicine , Baltimore, Maryland.
authors.forename: Angelo H
authors.initials: AH
authors.lastname: All
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002490:Central Nervous System / Q000293:injuries / Q000503:physiopathology; D004195:Disease Models, Animal; D005073:Evoked Potentials, Somatosensory; D005260:Female; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods; D000069451:Long Term Adverse Effects; D008991:Monitoring, Physiologic; D009043:Motor Activity; D000066829:Neuroprotection; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000523:psychology / Q000628:therapy; D013997:Time Factors