Hypothermia as a Neuroprotectant for Neurorehabilitation Eligible Patients: State of the Art Review and Update
Article Sidebar
Published
Mar 26, 2024
Downloads
Download data is not yet available.
Submit your own article
Register as an author to reserve your spot in the next issue of the Medical Research Archives.
Author RegistrationJoin the Society
The European Society of Medicine is more than a professional association. We are a community. Our members work in countries across the globe, yet are united by a common goal: to promote health and health equity, around the world.
Join Europe’s leading medical society and discover the many advantages of membership, including free article publication.
MembershipMain Article Content
Abstract
Applying therapeutic hypothermia (TH) for the purposes of neuroprotection, originally termed “hibernation,” started nearly 100 years ago. As advances in the medical and surgical management of patients with neurotrauma has increased survivability and minimized primary damage, significant research has been directed at identifying neuroprotective mechanisms that might mitigate the secondary damage which leads to neurological worsening and impedes recovery. As therapeutic hypothermia cooling systems have improved to the point where it is practical and safe for general application, interest in providing such treatment in conditions such as spinal cord injury, traumatic brain injury, stroke, and cardiac arrest has increased. This manuscript will review the mechanisms by which therapeutic hypothermia mitigates secondary neurological injury, the clinical scenarios where therapeutic hypothermia is being applied via Spinal Cord Injury (SCI), Traumatic Brain Injury (TBI), and Stroke (CVA), and review published studies utilizing therapeutic hypothermia for central nervous system neuroprotection in translational studies.
Keywords:
Spinal Cord Injury, Hypothermia, Neuroprotection, ASIA score, Trauma, Methylprednisolone, Stroke, Traumatic Brain Injury, TBI
Article Details
How to Cite
DALAL, Kevin L. et al.
Hypothermia as a Neuroprotectant for Neurorehabilitation Eligible Patients: State of the Art Review and Update.
Medical Research Archives, [S.l.], v. 12, n. 3, mar. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5202>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i3.5202.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Babe J, Delgado F. Otogenous cerebral abscess treated by surgical intervention and hibernation. Acta oto-rino-laringologica ibero-americana. 1956;7:212-220
2. Henderson AR Temple F. Uncomfortable crusader and Harbinger of human refrigeration 1895-1963. 1963;J Neurosurg 20:627-634.
3. Zdravev P. Treatment of cerebral hernia following surgery of an otogenous brain abscess. Les Annales d'oto-laryngologie. 1951;68:201-205.
4. Busto R, Dietrich WD, Globus MY, Ginsberg MD. The importance of brain temperature in cerebral ischemic injury. Stroke. 1989;20:1113-1114.
5. Metz C, Holzschuh M, Bein T, Woertgen C, Frey A, Frey I, Taeger K, Brawanski A. Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects. J Neurosurg. 1996;85:533-541.
6. Clifton GL, Allen S, Barrodale P, Plenger P, Berry J, Koch S, Fletcher J, Hayes RL, Choi SC. A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma. 1993;10:263-271; discussion 273.
7. Faridar A, Bershad EM, Emiru T, Iaizzo PA, Suarez JI, Divani AA. Therapeutic hypothermia in stroke and traumatic brain injury. Frontiers in Neurology. 2011;2:80
8. Sessler DI. Temperature monitoring and perioperative thermoregulation. Anesthesiology. 2008;109:318-338.
9. Jessen K. An assessment of human regulatory nonshivering thermogenesis. Acta anaesthesiologica Scandinavica. 1980;4:138-143.
10. Yenari M, Wijman C, Steinberg G. Effects of hypothermia on cerebral metabolism, blood flow, and autoregulation. In: Mayer S, Sessler D (eds) Therapeutic hypothermia. Marcel Dekker, New York. 2008;141-178
11. Varon J, Acosta P. Therapeutic hypothermia: past, present, and future. Chest. 2008;133:1267-1274.
12. Martinez-Arizala A, Green B (1992) Hypothermia in spinal cord injury. J Neurotrauma 9:S497-S505
13. Yu C, Jimenez O, Marcillo A, Weider B, Bangerter K, Dietrich W, Castro S, Yezierski R. Beneficial effects of modest systemic hypothermia on locomotor function and histopathological damage following contusion-induced spinal cord injury in rats. J Neurosurg (Spine). 2000;93: 1 Suppl 85–93
14. Chatzipantelli K, Yanagawa Y, Marcillo A, Kraydieh S, Dietrich W (2000) Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. J Neurotrauma 17:321-332
15. Westergren H, Farooque M, Olsson Y, Holtz A (2000) Motor function changes in the rat following severe spinal cord injury. Does treatment with moderate systemic hypothermia improve functional outcome? Acta Neurochir (Wien) 142:567-573
16. Marsala M, Sorkin L, Yaksh T. Transient spinal ischemia in rat: Characterization of spinal cord blood flow, extracellular amino acid release, and concurrent histopathological damage. J Cereb Blood Flow Metab. 1994;14(4):604-14. Doi:10.1038/jcbfm https://pubmed.ncbi.nlm.nih.gov/8014207/
17. You JS, Kim JY, Yenari MA. Therapeutic hypothermia for stroke: Unique challenges at the bedside. Front Neurol. 2022 Oct 3;13:951586. Doi: 10.3389/fneur.2022.951586. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575992/
18. Bernard SA, Mac CJB, Buist M. Experience with prolonged induced hypothermia in severe head injury. Critical Care. 1999;3:167-172.
19. Sunde K, Pytte M, Jacobsen D, Mangschau A, Jensen LP, Smedsrud C, Draegni T, Steen PA. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 2007;73:29-39.
20. Seule M, Muroi C, Sikorski C, Hugelshofer M, Winkler K, Keller E. Therapeutic hypothermia reduces middle cerebral artery flow velocity in patients with severe aneurysmal subarachnoid hemorrhage. Neurocritical care. 2014;20(2):255-62. Doi: 10.1007/s12028-013-9927-x.
21. Todd MM, Hindman BJ, Clarke WR, Torner JC (2005) Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med 352:135-145
22. Sherman AL, Wang MY. Hypothermia as a clinical neuroprotectant. Phys Med Rehabil Clin N Am. 2014 Aug;25(3):519-29, vii. Doi: 10.1016/j.pmr.2014.04.003. https://pubmed.ncbi.nlm.nih.gov/25064786/.
23. Vedantam A, Levi AD. Hypothermia for Acute Spinal Cord Injury. Neurosurg Clin N Am. 2021 Jul;32(3):377-387.
Doi: 10.1016/j.nec.2021.03.009
https://pubmed.ncbi.nlm.nih.gov/34053725/
24. Polderman KH, Callaghan J. Equipment review: cooling catheters to induce therapeutic hypothermia? Crit Care. 2006;10(6):234. Doi: 10.1186/cc5023 https://pubmed.ncbi.nlm.nih.gov/17096865/
25. Jain A, Gray M, Slisz S, Haymore J, Badjatia N, Kulstad E. Shivering Treatments for Targeted Temperature Management: A Review. J Neurosci Nurs. 2018 Apr;50(2):63-67. Doi: 10.1097/JNN.0000000000000340. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882245/
26. Blondin NA. Diagnosis and management of periodic hypothermia. Neurol Clin Pract.2014 Feb;4(1):26-33.
Doi: 10.1212/01.CPJ.0000437350.47610.3a https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765588/
27. Kranke P, Eberhart L, Roewer N, Tramer M (2002) Pharmacologic treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg 2002;94:453-460.
28. Cappuccino A, Bisson L, Carpenter B, Marzo J, Dietrich W, Cappuccino H. The use of systemic hypothermia for the treatment of an acute cervical spinal cord injury in a professional football player. Spine. 2010;35:E57-E62.
29. Albin M, White R, Acosta-Rica G, Yashon D. Study of functional recovery produced by delayed localized cooling of spinal cord injury in primates. J Neurosurg. 1968;29:113-120.
30. Albin M, White R, Yashon D, Harris L (1969) Effects of cooling on spinal cord trauma.J Trauma. 1969;9:1000-1008.
31. Zhu L. Hypothermia Used in Medical Applications for Brain and Spinal Cord Injury Patients. Adv Exp Med Biol. 2018;1097:295-319. Doi: 10.1007/978-3-319-96445-4_16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575992/
32. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med. 1990;322:1405-1411.
33. Bracken MB, Shepard MJ, Collins WF, Jr., Holford TR, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon JC, Marshall LF, et al. Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study. J Neurosurg.1992;76:23-31.
34. Bracken MB, Shepard MJ, Hellenbrand KG, Collins WF, Leo LS, Freeman DF, Wagner FC, Flamm ES, Eisenberg HM, Goodman JH, et al. Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study. J Neurosurg. 1985;63:704-713.
35. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL, Jr., Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 1994;277:1597-1604.
36. Hurlbert R (2001) The role of steroids in acute spinal cord injury: an evidence-based analysis. Spine 26:S55.
37. Hugenholtz H, Cass DE, Dvorak MF, Fewer DH, Fox RJ, Izukawa DM, Lexchin J, Tuli S, Bharatwal N, Short C. High-dose methylprednisolone for acute closed spinal cord injury--only a treatment option. Can J Neurol Sci. 2002;29:227-235.
38. Cappuccino A, Bisson LJ, Carpenter B, Snyder, Cappuccino H. Systemic Hypothermia as Treatment for an Acute Cervical Spinal Cord Injury in a Professional Football Player: 9-Year Follow-Up. Am J Ortho. 2017 Mar/Apr;E79-82.
39. Martinez-Arizala A, Green B. Hypothermia in spinal cord injury. J Neurotrauma.1992;9:S497-S505.
40. Dietrich WD, Levi AD, Wang M, Green BA. Hypothermic treatment for acute spinal cord injury. Neurotherapeutics. 2011 Apr;8(2):229-39. Doi: 10.1007/s13311-011- 0035-3. https://pubmed.ncbi.nlm.nih.gov/21416406/
41. Chatzipantelli K, Yanagawa Y, Marcillo A, Kraydieh S, Dietrich W. Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. J Neurotrauma. 2000;17:321-332.
42. Pearse D, Lo T, Cho K, Lynch M, Garg M, Marcillo A, Sanchez A, Cruz Y, Dietrich W. Histopathological and behavioral characterization of a novel cervical spinal cord displacement contusion in the rat. Neurotrauma. 2005;22:680-702.
43. Meyer O, Tilson H, Byrd W, Riley M (1979) A method for the routine assessment of fore- and hindlimb strength of rats and mice. Neurobehav Toxicol. 1979;1:233-236.
44. Hosier, H., Peterson, D.N., Tsymbalyuk, O., Keledjian, K., Smith, B., Ivanova, S., Gerzanich, V., Popovich, P.G., & Simard, J.M. A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury. Journal of Neurotrauma. 2015; 32, 1633 - 1644.
45. Xu X, Li N, Zhu L, Zhou Y, Cheng H. Beneficial effects of local profound hypothermia and the possible mechanism after experimental spinal cord injury in rats. J Spinal Cord Med. 2016;39(2):220-8.
Doi: 10.1179/2045772315Y.0000000051 https://pubmed.ncbi.nlm.nih.gov/26322652/
46. Jorge A, Fish EJ, Dixon CE, Hamilton KD, Balzer J, Thirumala P. The Effect of Prophylactic Hypothermia on Neurophysiological and Functional Measures in the Setting of Iatrogenic Spinal Cord Impact Injury. World Neurosurg. 2019 Sep;129:e607-e613. Doi:10.1016/j.wneu.2019.05.229. https://pubmed.ncbi.nlm.nih.gov/31158549/
47. Ransom SC, Brown NJ, Pennington ZA, Lakomkin N, Mikula AL, Bydon M, Elder BD. Hypothermia Therapy for Traumatic Spinal Cord Injury: An Updated Review. J Clin Med. 2022 Mar 13;11(6):1585. Doi: 10.3390/jcm11061585. https://pubmed.ncbi.nlm.nih.gov/35329911/
48. Levi A, Green B, Wang M, Dietrich D, Brindle T, Vanni S, Casella G, Elhammady G, Jagid J. Clinical application of modest hypothermia after spinal cord injury. J Neurotrauma. 2009;26:407-415.
49. Dididze M, Green BA, Dietrich WD, Vanni S, Wang MY, Levi AD. Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study. Spinal Cord. 2013 May;51(5):395-400.
Doi: 10.1038/sc.2012.161. https://pubmed.ncbi.nlm.nih.gov/23247015/
50. Shin HK, Park JH, Roh SW, Jeon SR. Meta-Analysis on the Effect of Hypothermia in Acute Spinal Cord Injury. Neurospine. 2022 Sep;19(3):748-756.
Doi: 10.14245/ns.2244444.222 https://pubmed.ncbi.nlm.nih.gov/36203299/
51. Al-Nashash H, All AH. Neuroprotective Role of Hypothermia in Acute Spinal Cord Injury. Biomedicines. 2022 Jan 4;10(1):104. Doi: 10.3390/biomedicines10010104 https://pubmed.ncbi.nlm.nih.gov/35052784/
52. Liu A, Zhang Z, Li A, Xue J, Effects of hypothermia and cerebral ischemia on cold- inducible RNA-binding protein mRNA expression in rat brain. Brain Res 2010:1347, 104–110.
53. van der Worp HB, Macleod MR, Bath PM, Demotes J, Durand-Zaleski I, Gebhardt B, Gluud C, Kollmar R, Krieger DW, Lees KR, Molina C, Montaner J, Roine RO, Petersson J, Staykov D, Szabo I, Wardlaw JM, Schwab S, Euro H. Y. P. i., EuroHYP-1: European multicenter, randomized, phase III clinical trial of therapeutic hypothermia plus best medical treatment vs. best medical treatment alone for acute ischemic stroke. Int J Stroke 2014;9, 642–645.
54. Yenari MA, Han HS, Neuroprotective mechanisms of hypothermia in brain ischaemia. Nat Rev Neurosci 2012;13, 267–278.
55. González-Ibarra FP, Varon J, López-Meza EG. Therapeutic hypothermia: critical review of the molecular mechanisms of action. Front Neurol. 2011 Feb 3;2:4.
Doi: 10.3389/fneur.2011.00004 https://pubmed.ncbi.nlm.nih.gov/21331282/
56. Wu L, Wu D, Yang T, Xu J, Chen J, Wang L, Xu S, Zhao W, Wu C, Ji X. Hypothermic neuroprotection against acute ischemic stroke: The 2019 update. J Cereb Blood Flow Metab. 2020 Mar;40(3):461-481.
57. Sun YJ, Ma S, Fan B, et al. Therapeutic hypothermia protects photoreceptors through activating Cirbp pathway. Neurochem Int 2019; 126: 86–95.
58. Liu J, Xue J, Zhang H, et al. Cloning, expression, and purification of cold inducible RNA-binding protein and its neuroprotective mechanism of action. Brain Res 2015; 1597: 189–195.
59. Li S, Zhang Z, Xue J, et al. Cold-inducible RNA binding protein inhibits H(2)O(2)- induced apoptosis in rat cortical neurons. Brain Res 2012; 1441: 47–52.
60. Zhuang RJ, Ma J, Shi X, et al. Cold-inducible proteinRBM3 protects UV irradiation- induced apoptosis in neuroblastoma cells by affecting p38 and JNK pathways and Bcl2 family proteins. J Mol Neurosci 2017; 63: 142–151.
61. Tuo QZ, Zhang ST, Lei P. Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications. Med Res Rev. 2022;Jan;42(1):259-305.
62. Wu C, Zhao W, An H, et al. Safety, feasibility, and potential efficacy of intraarterial selective cooling infusion for stroke patients treated with mechanical thrombectomy. J Cereb Blood Flow Metab 2018;38: 2251–2260.
63. Kurisu K, Kim JY, You J, Yenari MA. Therapeutic Hypothermia and Neuroprotection in Acute Neurological Disease. Curr Med Chem. 2019;26(29):5430-5455.
64. Kurisu K, Yenari MA. Therapeutic hypothermia for ischemic stroke; pathophysiology and future promise. Neuropharmacology. 2018;May 15;134(Pt B):302-309.
65. Hemmen TM, Lyden PD. Hypothermia after acute ischemic stroke. J Neurotrauma.2009 Mar;26(3):387-91.
66. Kim JY, Kim N, Lee JE, Yenari MA. Hypothermia Identifies Dynamin as a Potential Therapeutic Target in Experimental Stroke. Ther Hypothermia Temp Manag. 2017 Sep;7(3):171-177.
Doi: 10.1089/ther.2017.0005. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610406/
67. Kernie SG, Parent JM. Forebrain neurogenesis after focal Ischemic and traumatic brain injury. Neurobiol Dis. 2010 Feb;37(2):267-74.
Doi: 10.1016/j.nbd.2009.11.002. https://pubmed.ncbi.nlm.nih.gov/19909815/
68. Xiong M, Cheng GQ, Ma SM, Yang Y, Shao XM, Zhou WH. Post-ischemic hypothermia promotes generation of neural cells and reduces apoptosis by Bcl-2 in the striatum of neonatal rat brain. Neurochem Int. 2011 May;58(6):625-33.
Doi: 10.1016/j.neuint.2011.01.026. https://pubmed.ncbi.nlm.nih.gov/21300124/
69. Wang B, Wu D, Dornbos Iii D, Shi J, Ma Y, Zhang M, Liu Y, Chen J, Ding Y, Luo Y, Ji X. Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys. Neurol Res. 2016 Jun;38(6):545-52. Doi: 10.1080/01616412.2016.1187827. https://pubmed.ncbi.nlm.nih.gov/27320250/
70. Mattingly TK, Denning LM, Siroen KL, et al. Catheter based selective hypothermia reduces stroke volume during focal cerebral ischemia in swine. J Neurointerv Surg 2016; 8: 418–422.
71. Caroff J, King RM, Mitchell JE, et al. Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept. J Neurointerv Surg. Epub ahead of print 30 July 2019. Doi: 10.1136/neurintsurg-2019-015179.
72. Choi JH, Marshall RS, Neimark MA, et al. Selective brain cooling with endovascular intracarotid infusion of cold saline: a pilot feasibility study. AJNR Am J Neuroradiol 2010; 31: 928–934.
73. Chen J, Liu L, Zhang H, et al. Endovascular hypothermia in acute ischemic stroke: pilot study of selective intra-arterial cold saline infusion. Stroke 2016; 47:1933– 1935.
74. Myburgh JA, Cooper DJ, Finfer SR, Venkatesh B, Jones D, Higgins A, et al.Epidemiology and 12-month outcomes from traumatic brain injury in australia and new zealand. J Trauma. 2008;64:854–862. Doi: 10.1097/TA.0b013e3180340e77. https://pubmed.ncbi.nlm.nih.gov/18404048/
75. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21:375–378. Doi: 10.1097/00001199-200609000-00001. https://pubmed.ncbi.nlm.nih.gov/16983222/
76. Vik A, Nag T, Fredriksli OA, Skandsen T, Moen KG, Schirmer-Mikalsen K, et al. Relationship of “dose” of intracranial hypertension to outcome in severe traumatic brain injury. J Neurosurg. 2008;109:678–684.
Doi: 10.3171/JNS/2008/109/10/0678. https://pubmed.ncbi.nlm.nih.gov/18826355/
77. Miller JD, Butterworth JF, Gudeman SK, Faulkner JE, Choi SC, Selhorst JB, et al. Further experience in the management of severe head injury. J Neurosurg. 1981;54:289–299.
Doi: 10.3171/jns.1981.54.3.0289. https://pubmed.ncbi.nlm.nih.gov/7463128/
78. Andresen M, Gazmuri JT, Marín A, Regueira T, Rovegno M. Therapeutic hypothermia for acute brain injuries. Scand J Trauma Resusc Emerg Med. 2015 Jun 5;23:42. Doi: 10.1186/s13049-015-0121-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456795/
79. Henderson WR, Dhingra VK, Chittock DR, Fenwick JC, Ronco JJ. Hypothermia in the management of traumatic brain injury: A systematic review and meta-analysis. Intensive care medicine. 2003 Oct;29:1637-44.
80. Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM. Guidelines for the management of severe traumatic brain injury. Neurosurgery. 2017 Jan 1;80(1):6-15.
81. Cooper DJ, Nichol AD, Bailey M, Bernard S, Cameron PA, Pili-Floury S, Forbes A, Gantner D, Higgins AM, Huet O, Kasza J. Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR randomized clinical trial. Jama. 2018 Dec 4;320(21):2211-20. https://pubmed.ncbi.nlm.nih.gov/30357266/
82. Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, Wisniewski SR, DeKosky ST. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med. 1997 Feb 20;336(8):540-6. Doi: 10.1056/NEJM199702203360803. https://pubmed.ncbi.nlm.nih.gov/9023090/
83. Clifton, G.L., Valadka, A., Zygun, D., Coffey, C.S., Drever, P., Fourwinds, S., Janis, L.S., Wilde, E., Taylor, P., Harshman, K. and Conley, A., Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. The Lancet Neurology, 201110(2), pp.131-139.
84. Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst Rev. 2009;2:CD001048 https://pubmed.ncbi.nlm.nih.gov/19160187/
2. Henderson AR Temple F. Uncomfortable crusader and Harbinger of human refrigeration 1895-1963. 1963;J Neurosurg 20:627-634.
3. Zdravev P. Treatment of cerebral hernia following surgery of an otogenous brain abscess. Les Annales d'oto-laryngologie. 1951;68:201-205.
4. Busto R, Dietrich WD, Globus MY, Ginsberg MD. The importance of brain temperature in cerebral ischemic injury. Stroke. 1989;20:1113-1114.
5. Metz C, Holzschuh M, Bein T, Woertgen C, Frey A, Frey I, Taeger K, Brawanski A. Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects. J Neurosurg. 1996;85:533-541.
6. Clifton GL, Allen S, Barrodale P, Plenger P, Berry J, Koch S, Fletcher J, Hayes RL, Choi SC. A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma. 1993;10:263-271; discussion 273.
7. Faridar A, Bershad EM, Emiru T, Iaizzo PA, Suarez JI, Divani AA. Therapeutic hypothermia in stroke and traumatic brain injury. Frontiers in Neurology. 2011;2:80
8. Sessler DI. Temperature monitoring and perioperative thermoregulation. Anesthesiology. 2008;109:318-338.
9. Jessen K. An assessment of human regulatory nonshivering thermogenesis. Acta anaesthesiologica Scandinavica. 1980;4:138-143.
10. Yenari M, Wijman C, Steinberg G. Effects of hypothermia on cerebral metabolism, blood flow, and autoregulation. In: Mayer S, Sessler D (eds) Therapeutic hypothermia. Marcel Dekker, New York. 2008;141-178
11. Varon J, Acosta P. Therapeutic hypothermia: past, present, and future. Chest. 2008;133:1267-1274.
12. Martinez-Arizala A, Green B (1992) Hypothermia in spinal cord injury. J Neurotrauma 9:S497-S505
13. Yu C, Jimenez O, Marcillo A, Weider B, Bangerter K, Dietrich W, Castro S, Yezierski R. Beneficial effects of modest systemic hypothermia on locomotor function and histopathological damage following contusion-induced spinal cord injury in rats. J Neurosurg (Spine). 2000;93: 1 Suppl 85–93
14. Chatzipantelli K, Yanagawa Y, Marcillo A, Kraydieh S, Dietrich W (2000) Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. J Neurotrauma 17:321-332
15. Westergren H, Farooque M, Olsson Y, Holtz A (2000) Motor function changes in the rat following severe spinal cord injury. Does treatment with moderate systemic hypothermia improve functional outcome? Acta Neurochir (Wien) 142:567-573
16. Marsala M, Sorkin L, Yaksh T. Transient spinal ischemia in rat: Characterization of spinal cord blood flow, extracellular amino acid release, and concurrent histopathological damage. J Cereb Blood Flow Metab. 1994;14(4):604-14. Doi:10.1038/jcbfm https://pubmed.ncbi.nlm.nih.gov/8014207/
17. You JS, Kim JY, Yenari MA. Therapeutic hypothermia for stroke: Unique challenges at the bedside. Front Neurol. 2022 Oct 3;13:951586. Doi: 10.3389/fneur.2022.951586. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575992/
18. Bernard SA, Mac CJB, Buist M. Experience with prolonged induced hypothermia in severe head injury. Critical Care. 1999;3:167-172.
19. Sunde K, Pytte M, Jacobsen D, Mangschau A, Jensen LP, Smedsrud C, Draegni T, Steen PA. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 2007;73:29-39.
20. Seule M, Muroi C, Sikorski C, Hugelshofer M, Winkler K, Keller E. Therapeutic hypothermia reduces middle cerebral artery flow velocity in patients with severe aneurysmal subarachnoid hemorrhage. Neurocritical care. 2014;20(2):255-62. Doi: 10.1007/s12028-013-9927-x.
21. Todd MM, Hindman BJ, Clarke WR, Torner JC (2005) Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med 352:135-145
22. Sherman AL, Wang MY. Hypothermia as a clinical neuroprotectant. Phys Med Rehabil Clin N Am. 2014 Aug;25(3):519-29, vii. Doi: 10.1016/j.pmr.2014.04.003. https://pubmed.ncbi.nlm.nih.gov/25064786/.
23. Vedantam A, Levi AD. Hypothermia for Acute Spinal Cord Injury. Neurosurg Clin N Am. 2021 Jul;32(3):377-387.
Doi: 10.1016/j.nec.2021.03.009
https://pubmed.ncbi.nlm.nih.gov/34053725/
24. Polderman KH, Callaghan J. Equipment review: cooling catheters to induce therapeutic hypothermia? Crit Care. 2006;10(6):234. Doi: 10.1186/cc5023 https://pubmed.ncbi.nlm.nih.gov/17096865/
25. Jain A, Gray M, Slisz S, Haymore J, Badjatia N, Kulstad E. Shivering Treatments for Targeted Temperature Management: A Review. J Neurosci Nurs. 2018 Apr;50(2):63-67. Doi: 10.1097/JNN.0000000000000340. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882245/
26. Blondin NA. Diagnosis and management of periodic hypothermia. Neurol Clin Pract.2014 Feb;4(1):26-33.
Doi: 10.1212/01.CPJ.0000437350.47610.3a https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765588/
27. Kranke P, Eberhart L, Roewer N, Tramer M (2002) Pharmacologic treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg 2002;94:453-460.
28. Cappuccino A, Bisson L, Carpenter B, Marzo J, Dietrich W, Cappuccino H. The use of systemic hypothermia for the treatment of an acute cervical spinal cord injury in a professional football player. Spine. 2010;35:E57-E62.
29. Albin M, White R, Acosta-Rica G, Yashon D. Study of functional recovery produced by delayed localized cooling of spinal cord injury in primates. J Neurosurg. 1968;29:113-120.
30. Albin M, White R, Yashon D, Harris L (1969) Effects of cooling on spinal cord trauma.J Trauma. 1969;9:1000-1008.
31. Zhu L. Hypothermia Used in Medical Applications for Brain and Spinal Cord Injury Patients. Adv Exp Med Biol. 2018;1097:295-319. Doi: 10.1007/978-3-319-96445-4_16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575992/
32. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med. 1990;322:1405-1411.
33. Bracken MB, Shepard MJ, Collins WF, Jr., Holford TR, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon JC, Marshall LF, et al. Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study. J Neurosurg.1992;76:23-31.
34. Bracken MB, Shepard MJ, Hellenbrand KG, Collins WF, Leo LS, Freeman DF, Wagner FC, Flamm ES, Eisenberg HM, Goodman JH, et al. Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study. J Neurosurg. 1985;63:704-713.
35. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL, Jr., Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 1994;277:1597-1604.
36. Hurlbert R (2001) The role of steroids in acute spinal cord injury: an evidence-based analysis. Spine 26:S55.
37. Hugenholtz H, Cass DE, Dvorak MF, Fewer DH, Fox RJ, Izukawa DM, Lexchin J, Tuli S, Bharatwal N, Short C. High-dose methylprednisolone for acute closed spinal cord injury--only a treatment option. Can J Neurol Sci. 2002;29:227-235.
38. Cappuccino A, Bisson LJ, Carpenter B, Snyder, Cappuccino H. Systemic Hypothermia as Treatment for an Acute Cervical Spinal Cord Injury in a Professional Football Player: 9-Year Follow-Up. Am J Ortho. 2017 Mar/Apr;E79-82.
39. Martinez-Arizala A, Green B. Hypothermia in spinal cord injury. J Neurotrauma.1992;9:S497-S505.
40. Dietrich WD, Levi AD, Wang M, Green BA. Hypothermic treatment for acute spinal cord injury. Neurotherapeutics. 2011 Apr;8(2):229-39. Doi: 10.1007/s13311-011- 0035-3. https://pubmed.ncbi.nlm.nih.gov/21416406/
41. Chatzipantelli K, Yanagawa Y, Marcillo A, Kraydieh S, Dietrich W. Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. J Neurotrauma. 2000;17:321-332.
42. Pearse D, Lo T, Cho K, Lynch M, Garg M, Marcillo A, Sanchez A, Cruz Y, Dietrich W. Histopathological and behavioral characterization of a novel cervical spinal cord displacement contusion in the rat. Neurotrauma. 2005;22:680-702.
43. Meyer O, Tilson H, Byrd W, Riley M (1979) A method for the routine assessment of fore- and hindlimb strength of rats and mice. Neurobehav Toxicol. 1979;1:233-236.
44. Hosier, H., Peterson, D.N., Tsymbalyuk, O., Keledjian, K., Smith, B., Ivanova, S., Gerzanich, V., Popovich, P.G., & Simard, J.M. A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury. Journal of Neurotrauma. 2015; 32, 1633 - 1644.
45. Xu X, Li N, Zhu L, Zhou Y, Cheng H. Beneficial effects of local profound hypothermia and the possible mechanism after experimental spinal cord injury in rats. J Spinal Cord Med. 2016;39(2):220-8.
Doi: 10.1179/2045772315Y.0000000051 https://pubmed.ncbi.nlm.nih.gov/26322652/
46. Jorge A, Fish EJ, Dixon CE, Hamilton KD, Balzer J, Thirumala P. The Effect of Prophylactic Hypothermia on Neurophysiological and Functional Measures in the Setting of Iatrogenic Spinal Cord Impact Injury. World Neurosurg. 2019 Sep;129:e607-e613. Doi:10.1016/j.wneu.2019.05.229. https://pubmed.ncbi.nlm.nih.gov/31158549/
47. Ransom SC, Brown NJ, Pennington ZA, Lakomkin N, Mikula AL, Bydon M, Elder BD. Hypothermia Therapy for Traumatic Spinal Cord Injury: An Updated Review. J Clin Med. 2022 Mar 13;11(6):1585. Doi: 10.3390/jcm11061585. https://pubmed.ncbi.nlm.nih.gov/35329911/
48. Levi A, Green B, Wang M, Dietrich D, Brindle T, Vanni S, Casella G, Elhammady G, Jagid J. Clinical application of modest hypothermia after spinal cord injury. J Neurotrauma. 2009;26:407-415.
49. Dididze M, Green BA, Dietrich WD, Vanni S, Wang MY, Levi AD. Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study. Spinal Cord. 2013 May;51(5):395-400.
Doi: 10.1038/sc.2012.161. https://pubmed.ncbi.nlm.nih.gov/23247015/
50. Shin HK, Park JH, Roh SW, Jeon SR. Meta-Analysis on the Effect of Hypothermia in Acute Spinal Cord Injury. Neurospine. 2022 Sep;19(3):748-756.
Doi: 10.14245/ns.2244444.222 https://pubmed.ncbi.nlm.nih.gov/36203299/
51. Al-Nashash H, All AH. Neuroprotective Role of Hypothermia in Acute Spinal Cord Injury. Biomedicines. 2022 Jan 4;10(1):104. Doi: 10.3390/biomedicines10010104 https://pubmed.ncbi.nlm.nih.gov/35052784/
52. Liu A, Zhang Z, Li A, Xue J, Effects of hypothermia and cerebral ischemia on cold- inducible RNA-binding protein mRNA expression in rat brain. Brain Res 2010:1347, 104–110.
53. van der Worp HB, Macleod MR, Bath PM, Demotes J, Durand-Zaleski I, Gebhardt B, Gluud C, Kollmar R, Krieger DW, Lees KR, Molina C, Montaner J, Roine RO, Petersson J, Staykov D, Szabo I, Wardlaw JM, Schwab S, Euro H. Y. P. i., EuroHYP-1: European multicenter, randomized, phase III clinical trial of therapeutic hypothermia plus best medical treatment vs. best medical treatment alone for acute ischemic stroke. Int J Stroke 2014;9, 642–645.
54. Yenari MA, Han HS, Neuroprotective mechanisms of hypothermia in brain ischaemia. Nat Rev Neurosci 2012;13, 267–278.
55. González-Ibarra FP, Varon J, López-Meza EG. Therapeutic hypothermia: critical review of the molecular mechanisms of action. Front Neurol. 2011 Feb 3;2:4.
Doi: 10.3389/fneur.2011.00004 https://pubmed.ncbi.nlm.nih.gov/21331282/
56. Wu L, Wu D, Yang T, Xu J, Chen J, Wang L, Xu S, Zhao W, Wu C, Ji X. Hypothermic neuroprotection against acute ischemic stroke: The 2019 update. J Cereb Blood Flow Metab. 2020 Mar;40(3):461-481.
57. Sun YJ, Ma S, Fan B, et al. Therapeutic hypothermia protects photoreceptors through activating Cirbp pathway. Neurochem Int 2019; 126: 86–95.
58. Liu J, Xue J, Zhang H, et al. Cloning, expression, and purification of cold inducible RNA-binding protein and its neuroprotective mechanism of action. Brain Res 2015; 1597: 189–195.
59. Li S, Zhang Z, Xue J, et al. Cold-inducible RNA binding protein inhibits H(2)O(2)- induced apoptosis in rat cortical neurons. Brain Res 2012; 1441: 47–52.
60. Zhuang RJ, Ma J, Shi X, et al. Cold-inducible proteinRBM3 protects UV irradiation- induced apoptosis in neuroblastoma cells by affecting p38 and JNK pathways and Bcl2 family proteins. J Mol Neurosci 2017; 63: 142–151.
61. Tuo QZ, Zhang ST, Lei P. Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications. Med Res Rev. 2022;Jan;42(1):259-305.
62. Wu C, Zhao W, An H, et al. Safety, feasibility, and potential efficacy of intraarterial selective cooling infusion for stroke patients treated with mechanical thrombectomy. J Cereb Blood Flow Metab 2018;38: 2251–2260.
63. Kurisu K, Kim JY, You J, Yenari MA. Therapeutic Hypothermia and Neuroprotection in Acute Neurological Disease. Curr Med Chem. 2019;26(29):5430-5455.
64. Kurisu K, Yenari MA. Therapeutic hypothermia for ischemic stroke; pathophysiology and future promise. Neuropharmacology. 2018;May 15;134(Pt B):302-309.
65. Hemmen TM, Lyden PD. Hypothermia after acute ischemic stroke. J Neurotrauma.2009 Mar;26(3):387-91.
66. Kim JY, Kim N, Lee JE, Yenari MA. Hypothermia Identifies Dynamin as a Potential Therapeutic Target in Experimental Stroke. Ther Hypothermia Temp Manag. 2017 Sep;7(3):171-177.
Doi: 10.1089/ther.2017.0005. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610406/
67. Kernie SG, Parent JM. Forebrain neurogenesis after focal Ischemic and traumatic brain injury. Neurobiol Dis. 2010 Feb;37(2):267-74.
Doi: 10.1016/j.nbd.2009.11.002. https://pubmed.ncbi.nlm.nih.gov/19909815/
68. Xiong M, Cheng GQ, Ma SM, Yang Y, Shao XM, Zhou WH. Post-ischemic hypothermia promotes generation of neural cells and reduces apoptosis by Bcl-2 in the striatum of neonatal rat brain. Neurochem Int. 2011 May;58(6):625-33.
Doi: 10.1016/j.neuint.2011.01.026. https://pubmed.ncbi.nlm.nih.gov/21300124/
69. Wang B, Wu D, Dornbos Iii D, Shi J, Ma Y, Zhang M, Liu Y, Chen J, Ding Y, Luo Y, Ji X. Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys. Neurol Res. 2016 Jun;38(6):545-52. Doi: 10.1080/01616412.2016.1187827. https://pubmed.ncbi.nlm.nih.gov/27320250/
70. Mattingly TK, Denning LM, Siroen KL, et al. Catheter based selective hypothermia reduces stroke volume during focal cerebral ischemia in swine. J Neurointerv Surg 2016; 8: 418–422.
71. Caroff J, King RM, Mitchell JE, et al. Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept. J Neurointerv Surg. Epub ahead of print 30 July 2019. Doi: 10.1136/neurintsurg-2019-015179.
72. Choi JH, Marshall RS, Neimark MA, et al. Selective brain cooling with endovascular intracarotid infusion of cold saline: a pilot feasibility study. AJNR Am J Neuroradiol 2010; 31: 928–934.
73. Chen J, Liu L, Zhang H, et al. Endovascular hypothermia in acute ischemic stroke: pilot study of selective intra-arterial cold saline infusion. Stroke 2016; 47:1933– 1935.
74. Myburgh JA, Cooper DJ, Finfer SR, Venkatesh B, Jones D, Higgins A, et al.Epidemiology and 12-month outcomes from traumatic brain injury in australia and new zealand. J Trauma. 2008;64:854–862. Doi: 10.1097/TA.0b013e3180340e77. https://pubmed.ncbi.nlm.nih.gov/18404048/
75. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21:375–378. Doi: 10.1097/00001199-200609000-00001. https://pubmed.ncbi.nlm.nih.gov/16983222/
76. Vik A, Nag T, Fredriksli OA, Skandsen T, Moen KG, Schirmer-Mikalsen K, et al. Relationship of “dose” of intracranial hypertension to outcome in severe traumatic brain injury. J Neurosurg. 2008;109:678–684.
Doi: 10.3171/JNS/2008/109/10/0678. https://pubmed.ncbi.nlm.nih.gov/18826355/
77. Miller JD, Butterworth JF, Gudeman SK, Faulkner JE, Choi SC, Selhorst JB, et al. Further experience in the management of severe head injury. J Neurosurg. 1981;54:289–299.
Doi: 10.3171/jns.1981.54.3.0289. https://pubmed.ncbi.nlm.nih.gov/7463128/
78. Andresen M, Gazmuri JT, Marín A, Regueira T, Rovegno M. Therapeutic hypothermia for acute brain injuries. Scand J Trauma Resusc Emerg Med. 2015 Jun 5;23:42. Doi: 10.1186/s13049-015-0121-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456795/
79. Henderson WR, Dhingra VK, Chittock DR, Fenwick JC, Ronco JJ. Hypothermia in the management of traumatic brain injury: A systematic review and meta-analysis. Intensive care medicine. 2003 Oct;29:1637-44.
80. Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM. Guidelines for the management of severe traumatic brain injury. Neurosurgery. 2017 Jan 1;80(1):6-15.
81. Cooper DJ, Nichol AD, Bailey M, Bernard S, Cameron PA, Pili-Floury S, Forbes A, Gantner D, Higgins AM, Huet O, Kasza J. Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR randomized clinical trial. Jama. 2018 Dec 4;320(21):2211-20. https://pubmed.ncbi.nlm.nih.gov/30357266/
82. Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, Wisniewski SR, DeKosky ST. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med. 1997 Feb 20;336(8):540-6. Doi: 10.1056/NEJM199702203360803. https://pubmed.ncbi.nlm.nih.gov/9023090/
83. Clifton, G.L., Valadka, A., Zygun, D., Coffey, C.S., Drever, P., Fourwinds, S., Janis, L.S., Wilde, E., Taylor, P., Harshman, K. and Conley, A., Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. The Lancet Neurology, 201110(2), pp.131-139.
84. Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst Rev. 2009;2:CD001048 https://pubmed.ncbi.nlm.nih.gov/19160187/