Behavioral Improvements with Posttraumatic Hypothermia

  • Nariyuki Hayashi
  • Dalton W. Dietrich


The histopathological assessment of the injured brain is considered to be an important endpoint for evaluating neuroprotective strategies. Nevertheless, from a clinical perspective, it is critical to determine whether histopathological protection correlates with improved functional and behavioral performance. Clifton and colleagues [4] first reported that posttraumatic hypothermia (30° and 33°C) improved beam balance and beam walking tasks compared to normothermic rats (38°C) after midline F-P brain injury (2.10–2.25 atm). Subsequent studies using the F-P model demonstrated that posttraumatic hypothermia (30°C/3h) improved both sensorimotor and cognitive behavioral deficits compared to normothermic rats [2,14].In one study, the protective effect of hypothermia was not seen if the onset of hypothermia was delayed by 30min [14]. In a cortical impact model, postischemic hypothermia treatment improved beam balance and spatial memory performance [6]. Cognitive deficits including memory impairments are commonly observed in humans suffering brain injury.


Traumatic Brain Injury Spinal Cord Injury Therapeutic Hypothermia Mild Hypothermia Spinal Cord Ischemia 
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  1. 1.
    Albin MS, White RJ, Locke GE (1965) Treatment of spinal cord trauma by selective hypothermic perfusion. Surg Forum 16:423–424PubMedGoogle Scholar
  2. 2.
    Bramlett H, Green EJ, Dietrich WD, Busto R, Globus MY-T, Ginsberg MD (1995) Post-traumatic brain hypothermia provides protection from sensorimotor and cognitive behavioral deficits. J Neurotrauma 12:289–298PubMedCrossRefGoogle Scholar
  3. 3.
    Clifton GL (1995) Systemic hypothermia in treatment of severe brain injury: a review and update. J Neurotrauma 12:923–927PubMedCrossRefGoogle Scholar
  4. 4.
    Clifton G, Jiang JY, Lyeth BG, et al (1991) Marked protection by moderate hypothermia after experimental traumatic brain injury. J Cereb Blood Flow Metals 11:114–121CrossRefGoogle Scholar
  5. 5.
    Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KR Jr, Muizelaar JP, Wagner FC, Marion DW, Luerssen TG, Chesnut RM, Schwartz M (2001) Lack of effect of induction of hypothermia after acute brain injury. N Eng J Med 344:556–563CrossRefGoogle Scholar
  6. 6.
    Dixon CE, Markgraf CG, Angileri F, Pike BP, Wolfson B, Newcomb JK, Bismar MM, Blanco AJ, Clifton GL, Hayes RL (1998) Protective effects of moderate hypothermia on behavioral deficits but not necrotic cavitation following cortical impact injury in the rat. J Neurotrauma 15: 95–103PubMedCrossRefGoogle Scholar
  7. 7.
    Green BA, Khan T, Raimondi AJ (1973) Local hypothermia as treatment of experimentally induced spinal cord contusion: quantitative analysis of beneficent effect. Surg Forum 24:436–438PubMedGoogle Scholar
  8. 8.
    Hansebout RR, Kuehner EF, Romero-Sierra C (1976) Effects of local hypothermia and of steroids upon recovery from experimental spinal cord compression injury. Surg Neurol 6:243–246Google Scholar
  9. 9.
    Herold JA, Kron IL, Langenburg SE, Blackbourne LH, Tribble CG (1994) Complete prevention of postischemic spinal cord injury by means of regional infusion with hypothermic saline and adenosine. J Thorac Cardiovasc Surg 107:536–541PubMedGoogle Scholar
  10. 10.
    Jiang J-Y, Yu M-K, Zhu C (2000) Effect of long-term hypothermia therapy in patients with severe traumatic brain injury: 1-year follow-up review of 87 cases. J Neurosurg 93:546–549PubMedCrossRefGoogle Scholar
  11. 11.
    Kakinohama M, Taira Y, Marsala M (1999) The effect of graded postischemic spinal cord hypothermia on neurological outcome and histopathology after transient spinal ischemia in rat. Anesthesiology 90:789–798CrossRefGoogle Scholar
  12. 12.
    Karibe H, Chen J, Zarow GJ, Graham SH, Weinstein PR (1994) Delayed induction of mild hypothermia to reduce infarct volume after temporary middle cerebral artery occlusion in rats. J Neurosurg 80:112–119PubMedCrossRefGoogle Scholar
  13. 13.
    Kuchnor EF, Hansebout RR (1976) Combined steroid and hypothermia treatment of experimental spinal cord injury. Surg Neurol 7:371–376Google Scholar
  14. 14.
    Lyeth BG, Jiang JY, Shanliang L (1993) Behavioral protection by moderate hypothermia initiated after experimental traumatic brain injury. J Neurotrauma 10:57–64PubMedCrossRefGoogle Scholar
  15. 15.
    Marion DW, Obrist WD, Carlier PM, Penrod LE, Darby JM (1993) The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report. J Neurosurg 79:354–362PubMedCrossRefGoogle Scholar
  16. 16.
    Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, Wisniewki SR, DeKosky ST (1997) Treatment of traumatic brain injury with moderate hypothermia. N Eng J Med 336:540–546CrossRefGoogle Scholar
  17. 17.
    Marsala M, Vanicky I, Yaksh TL (1994) Effect of graded hypothermia (27°–-34°C) on behavioral function, histopathology, and spinal cord blood flow after spinal ischemia in rat. Stroke 25:2038–2046PubMedCrossRefGoogle Scholar
  18. 18.
    Marsala M, Galik J, Ishikawa T, Yaksh TL (1997) Technique of selective spinal cord cooling in rat: methodology and application. J Neurosci Methods 74:97–106PubMedCrossRefGoogle Scholar
  19. 19.
    Martinez-Arizala A, Green BA (1992) Hypothermia in spinal cord injury. J Neurotrauma 9:S497–S505PubMedGoogle Scholar
  20. 20.
    Matsumoto M, Iida Y, Sakabe T, Sano T, Ishikawa T, Nakakimura K (1997) Mild and moderate hypothermia provide better protection than a burst-suppression dose of thiopental against ischemic spinal cord injury in rabbits. Anesthesiology 86:1120–1127PubMedCrossRefGoogle Scholar
  21. 21.
    Resnick DK, Marion DW,Darby JM (1994) The effect of hypothermia on the incidence of delayed traumatic intra cerebral hemorrhage. J Neurosurg 34:252–256CrossRefGoogle Scholar
  22. 22.
    Robertson CS, Folz R, Grossman RG, Goodman JC (1986) Protection against experimental ischemic spinal cord injury. J Neurosurg 64:633–642PubMedCrossRefGoogle Scholar
  23. 23.
    Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, Sugimoto T (1993) Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 79:363–368PubMedCrossRefGoogle Scholar
  24. 24.
    Shiozaki T, Sugimoto H, Taneda M, Oda J, Tanaka H, Hiraide A, Shimazu T (1998) Selection of severely head injured patients for mild hypothermia therapy. J Neurosurg 89:206–211PubMedCrossRefGoogle Scholar
  25. 25.
    Shiozaki T, Hayakata T, Taneda M, Nakajima Y, Hashiguchi N, Fujimi S, Nakamori Y,Tanaka H, Shimazu T, Sugimoto H, Mild hypothermia study group in Japan (2001) A multi center prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. J Neurosurg 94:50–54PubMedCrossRefGoogle Scholar
  26. 26.
    Svensson LG (1999) An approach to spinal cord protection during descending or thoracoabdominal aortic repairs. Ann Thorac 67:1935–1936CrossRefGoogle Scholar
  27. 27.
    Tator CH, Deecke L (1973) Value of normothermic perfusion, hypothermic perfusion, and durotomy in the treatment of experimental acute spinal cord trauma. J Neurosurg 39:52–64PubMedCrossRefGoogle Scholar
  28. 28.
    Vanicky I, Marsala M, Galik J, Marsala J (1993) Epidural perfusion cooling protection against protracted spinal cord ischemia in rabbits. J Neurosurg 79:736–741PubMedCrossRefGoogle Scholar
  29. 29.
    Wells JD, Hansebout RR (1978) Local hypothermia in experimental spinal cord trauma. Surg Neurol 10:200–204PubMedGoogle Scholar
  30. 30.
    Yu CG, Marcillo AE, Dietrich WD, Fairbanks CA, Wilcox GL, Yezierski RP (1999) Beneficial effects of hypothermia and/or agmatine on locomotor outcome following contusion spinal cord injury. Soc Neurosci Abstr 29:268Google Scholar

Copyright information

© Springer Japan 2004

Authors and Affiliations

  • Nariyuki Hayashi
    • 1
    • 2
  • Dalton W. Dietrich
    • 3
    • 4
  1. 1.Nihon University Emergency Medical CenterTokyoJapan
  2. 2.Department of Emergency and Critical Care MedicineNihon University School of MedicineTokyoJapan
  3. 3.Department of Neurological Surgery, Neurology and Cell Biology and AnatomyUniversity of Miami School of MedicineMiamiUSA
  4. 4.The Miami Project to Cure ParalysisMiamiUSA

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