The role of therapeutic hypothermia in acute spinal cord injury
Keywords:
therapeutic hypothermia, spinal cord injury
Abstract
Ancient Egyptians were the first to use therapeutic hypothermia; thus, it is not a new concept. The term “hypothermia” is defined as a core temperature < 35° C (95° F). A spinal cord injury (SCI) is considered as one of the most significant injuries someone can endure since damage to just a small area of the body could implicate multiple body systems. A wide range of different mechanisms leading to tissue damage in the cord could cause injury.
Various early clinical SCI studies have investigated therapeutic hypothermia as a treatment strategy and have shown that if applied according to certain optimized parameters, the clinical use of hypothermia is most successful. Such parameters are temperature, time from injury to initiation of cooling, and rewarming time. Both local hypothermia and systemic hypothermia could be beneficial for acute SCI according to experimental evidence and some clinical evidence. The underlying mechanisms by which small reductions in central nervous system temperature can improve outcomes in brain and spinal cord injury models are still under investigation.
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References
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2. Yamashita C, Nakagiri K, Yamashita T et al. Mild hypothermia for temporary brain ischemia during cardiopulmonary support systems: report of three cases. Surg. Today. 1999;29(2):182-5.
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7. Bricolo A, Ore GD, Pian R et al. Local cooling in spinal cord injury. Surg Neurol. 1976; 6:101–106.
8. Demian YK, White RJ, Yashon D, et al. Anaesthesia for laminectory and localized cord cooling in acute cervical spine injury. Report of three cases. Br J Anaesth. 1971; 43:973–979.
9. Casas CE, Herrera LP, Prusmack C et al. Effects of epidural hypothermic saline infusion on locomotor outcome and tissue prevention after moderate thoracic spinal cord contusion in rats. Spine. 2005; 2:308–318.
10. Wells JD, Hansebout RR. Local hypothermia in experimental spinal cord trauma. Surg Neurol. 1978; 10:200–204
11. Ha KY, Kim YH. Neuroprotective effect of moderate epidural hypothermia after spinal cord injury in rats. Spine. 2008; 33:2059–65.
12. Hansebout RR, Kuchner EF. Effects of local hypothermia and of steroids upon recovery from experimental spinal cord compression injury. Surg Neurol. 1975; 4:531–536.
13. Kuchner EF, Hansebout RR. Combined steroid and hypothermia treatment of experimental spinal cord injury. Surg Neurol. 1976; 6:371–376.
14. Downey JA, Miller JM, Darling RC. Thermoregulatory responses to deep and superficial cooling in spinal man. J. Appl Physiol. 1969; 27:209–212.
15. Kranke P, Eberhart LH, Roewer N et al. Pharmacological treatment of postoperative shivering: a quantitative systemic review of randomized controlled trials. AnesthAnalg. 2002;94:453–460.
16. Berguer R, Porto J, Fedoronko B et al. Selective deep hypothermia of the spinal cord prevents paraplegia after aortic cross-clamping in the dog model. J Vasc Surg. 1992;15:6271.
17. Black JH, Davison JK, Cambria RP. Regional hypothermia with epidural cooling for prevention of spinal cord ischemic complications after thoracoabdominal aortic surgery. Semin Thorac Cardiovasc Surg. 2003;15:345–352.
18. Cambria RP, Davison JK. Regional hypothermia with epidural cooling for prevention of spinal cord ischemic complications after thoracoabdominal aortic surgery. Semin Thorac Cardiovasc Surg. 2000;13:315–324
19. Westergren H, Farooque M, Olsson Y et al. Spinal cord blood flow charges following systemic hypothermia and spinal cord compression injury: An experimental study in the rat using laser-Doppler flowmetry. Spinal Cord. 2001;39:74–84.
20. Marsala M, Vanicky I, Galik J et al. Panmyelic epidural cooling protects against ischemic spinal cord damage. J Surg Res. 1993;55:21–31.
21. Dimar JR, Shields CB, Zhang YP et al. The role of directly applied hypothermia in spinal cord injury. Spine. 2000;25:2294–2302.
22. Downey JA, Miller JM, Darling RC. Thermoregulatory responses to deep and superficial cooling in spinal man. J. Appl Physiol. 1969;27:209–212.
23. Botel U, Glaser E, Niedeggen A. The surgical treatment of acute spinal paralysed patients. Spinal Cord. 1997;35:420–428.
24. Dietrich WD, Atkins CM, Bramlett HM. Protection in animal models of brain and spinal cord injury with mild to moderate hypothermia. J Neurotrauma. 2009;26:301–312.
25. Marion D, Bullock MR. Current and future role of therapeutic hypothermia. J. Neurotrauma. 2009;26:455–467.
26. Martirosyan NL, Patel AA, Carotenuto A, et al. The role of therapeutic hypothermia in the management of acute spinal cord injury. Clin Neurol Neurosurg. 2017;154:79-88.
27. Ahmad FU, Wang MY, Levi AD. Hypothermia for acute spinal cord injury—areview. World Neurosurg. 2014;82(1-2):207-14.
28. Calver P, Braungardt T, Kupchik N, Jensen A, Cutler C. The big chill: improving the odds after cardiac arrest. RN. 2005 May;68(5):58-62; quiz 63.Review. PubMed PMID: 15931934.
29. Schwab S, Georgiadis D, Berrouschot J, et al. Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke. 2001;32(9):2033–2035.
30. Schubert A. Side effects of mild hypothermia. J Neurosurg Anesthesiol. 1995;7(2):139–147.
31. Dietrich WD, Busto R, Alonso O et al. Intraischemic but not postischemic brain hypothermia protects chronically following global forebrain ischemia in rats. J Cereb Blood Flow Metab. 1993;13(4):541–549
32. Colbourne F, Corbett D. Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection. J Neurosci. 1995;15(11):7250–7260.
33. Lo TP, Jr, Cho KS, Garg MS, et al. Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol. 2009;514(5):433–448.
34. Hansebout RR, Kuchner EF, Romero-Sierra C. Effects of local hypothermia and of steroids upon recovery from experimental spinal cord compression injury. Surg Neurol. 1975;4(6):531–536.
35. Casas CE, Herrera LP, Prusmack C et al. Effects of epidural hypothermic saline infusion on locomotor outcome and tissue preservation after moderate thoracic spinal cord contusion in rats. J Neurosurg Spine. 2005;2(3):308–318
36. Lyeth BG, Jiang JY, Liu S. Behavioral protection by moderate hypothermia initiated after experimental traumatic brain injury. J Neurotrauma. 1993;10(1):57–64
37. Koizumi H, Povlishock JT. Posttraumatic hypothermia in the treatment of axonal damage in an animal model of traumatic axonal injury. J Neurosurg. 1998;89(2):303–309.
38. Marion DW, White MJ. Treatment of experimental brain injury with moderate hypothermia and 21-aminosteroids. J Neurotrauma. 1996;13(3):139–147.
39. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. III. Prophylactic hypothermia. J Neurotrauma. 2007;24(Suppl 1):S21–25
40. Aibiki M, Maekawa S, Yokono S. Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans. Crit Care Med. 2000;28(12):3902–3906.
41. Qiu W, Zhang Y, Sheng H, et al. Effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy. J Crit Care. 2007;22(3):229–235
42. Dong H, Moody-Corbett F, Colbourne F, etal. Electrophysiological properties of CA1 neurons protected by postischemic hypothermia in gerbils. Stroke. 2001;32(3):788–795.
43. Zhao H, Wang JQ, Shimohata T, et al. Conditions of protection by hypothermia and effects on apoptotic pathways in a rat model of permanent middle cerebral artery occlusion. J Neurosurg. 2007;107(3):636–641.
44. Zhang Y, Lv Y, Ji W, et al. Therapeutic hypothermiaeffectively reduces elevated extracellular ascorbate concentrations caused byacute spinal cord injury. Artif Cells NanomedBiotechnol. 2019 Dec;47(1):22-29.doi: 10.1080/21691401.2018.1541136. Epub 2018 Dec 11. PubMed PMID: 30526134
45. Seupaul RA, Wilbur LG. Evidence-based emergency medicine. Does therapeutic hypothermia benefit survivors of cardiac arrest? Ann Emerg Med. 2011;58(3):282–283
46. Lotocki G, de Rivero Vaccari JP, Perez ER, et al. Alterations in blood-brain barrier permeability to large and small molecules and leukocyte accumulation after traumatic brain injury: effects of post-traumatic hypothermia. J Neurotrauma. 2009;26(7):1123–1134.
47. Morino T, Ogata T, Takeba J, et al. Microglia inhibition is a target of mild hypothermic treatment after the spinal cord injury. Spinal Cord. 2008;46(6):425–431
48. Small DL, Morley P, Buchan AM. Biology of ischemic cerebral cell death. Prog Cardiovasc Dis. 1999;42(3):185–207
49. Milde LN. Clinical use of mild hypothermia for brain protection: a dream revisited. J NeurosurgAnesthesiol. 1992;4(3):211–215.
50. Xu L, Yenari MA, Steinberg GK, et al. Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab. 2002;22(1):21–28
51. Wang J, Pearse DD. Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions. Int J Mol Sci. 2015;16(8):16848–16879
52. Sun YJ, Zhang ZY, Fan B, Li GY. Neuroprotection by Therapeutic Hypothermia. Front Neurosci. 2019 Jun 11;13:586. doi: 10.3389/fnins.2019.00586. eCollection2019. Review. PubMed PMID: 31244597; PubMed Central PMCID: PMC6579927.
53. Wang L, Jiang F, Li Q, He X, Ma J. Mild hypothermia combined with neural stem cell transplantation for hypoxic-ischemic encephalopathy: neuroprotective effects of combined therapy. Neural Regen Res. 2014 Oct 1;9(19):1745-52. doi:10.4103/1673-5374.143417.
54. Vishwakarma SK, Bardia A, Chandrakala L, et al. Enhanced neuroprotective effect of mild-hypothermia with VPA against ethanol-mediated neuronal injury. Tissue Cell. 2017 Dec;49(6):638-647. doi: 10.1016/j.tice.2017.09.004. Epub 2017 Sep 14. PubMed PMID: 28947065.
55. Barks JD, Liu YQ, Shangguan Y, Silverstein FS. Phenobarbital augments hypothermic neuroprotection. Pediatr Res. 2010 May;67(5):532-7. doi: 10.1203/PDR.0b013e3181d4ff4d. PubMed PMID: 20098339; PubMed Central PMCID: PMC2906127.
56. Gao XY, Huang JO, Hu YF, et al. Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury. Sci Rep. 2014 Nov 18;4:7091. doi: 10.1038/srep07091. Erratum in: Sci Rep.2015;5:12195. PubMed PMID: 25404538; PubMed Central PMCID: PMC4665348.
57. Tu Y, Miao XM, Yi TL, et al. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury. Neural Regen Res. 2016 Jun;11(6):931-6. doi:10.4103/1673-5374.184491. PubMed PMID: 27482221; PubMed Central PMCID: PMC4962590.
58. Zhu H, Meloni BP, Bojarski C, et al. Post-ischemic modest hypothermia (35 degrees C) combined with intravenous magnesium is more effective at reducing CA1 neuronal death than either treatment used alone following global cerebral ischemia in rats. Exp Neurol. 2005 Jun;193(2):361-8. PubMed PMID:15869938.
59. Ma D, Hossain M, Chow A, Arshad M, et al. Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia. Ann Neurol. 2005 Aug;58(2):182-93. PubMed PMID: 16049939.
2. Yamashita C, Nakagiri K, Yamashita T et al. Mild hypothermia for temporary brain ischemia during cardiopulmonary support systems: report of three cases. Surg. Today. 1999;29(2):182-5.
3. Peter J. Fagenholz, Edward A. Bittner, Chapter 76 - Hypothermia, Editor(s): Polly E. Parsons, Jeanine P. Wiener-Kronish, Critical Care Secrets (Fifth Edition), Mosby,2013, Pages 534-540, ISBN 9780323085007
4. Nick Webborn, Victoria Goosey-Tolfrey, Chapter 10 - Spinal cord injury, Editor(s): John P Buckley, In Advances in Sport and Exercise Science Series, Exercise Physiology in Special Populations, Churchill Livingstone,2008, Pages 309-334, ISBN 9780443103438
5. Maynard FM Jr, Bracken MB, Creasey G, et al. International Standards for Neurological and Functional Classification of Spinal Cord Injury. American Spinal Injury Association. Spinal Cord. 1997 May;35(5):266-74. PubMed PMID: 9160449.
6. Guest JD, Dietrich WD. Spinal cord ischemia and trauma. In: Tisherman SA, Sterz F, editors. Therapeutic hypothermia. New York: Springer; 2005. pp. 101–118
7. Bricolo A, Ore GD, Pian R et al. Local cooling in spinal cord injury. Surg Neurol. 1976; 6:101–106.
8. Demian YK, White RJ, Yashon D, et al. Anaesthesia for laminectory and localized cord cooling in acute cervical spine injury. Report of three cases. Br J Anaesth. 1971; 43:973–979.
9. Casas CE, Herrera LP, Prusmack C et al. Effects of epidural hypothermic saline infusion on locomotor outcome and tissue prevention after moderate thoracic spinal cord contusion in rats. Spine. 2005; 2:308–318.
10. Wells JD, Hansebout RR. Local hypothermia in experimental spinal cord trauma. Surg Neurol. 1978; 10:200–204
11. Ha KY, Kim YH. Neuroprotective effect of moderate epidural hypothermia after spinal cord injury in rats. Spine. 2008; 33:2059–65.
12. Hansebout RR, Kuchner EF. Effects of local hypothermia and of steroids upon recovery from experimental spinal cord compression injury. Surg Neurol. 1975; 4:531–536.
13. Kuchner EF, Hansebout RR. Combined steroid and hypothermia treatment of experimental spinal cord injury. Surg Neurol. 1976; 6:371–376.
14. Downey JA, Miller JM, Darling RC. Thermoregulatory responses to deep and superficial cooling in spinal man. J. Appl Physiol. 1969; 27:209–212.
15. Kranke P, Eberhart LH, Roewer N et al. Pharmacological treatment of postoperative shivering: a quantitative systemic review of randomized controlled trials. AnesthAnalg. 2002;94:453–460.
16. Berguer R, Porto J, Fedoronko B et al. Selective deep hypothermia of the spinal cord prevents paraplegia after aortic cross-clamping in the dog model. J Vasc Surg. 1992;15:6271.
17. Black JH, Davison JK, Cambria RP. Regional hypothermia with epidural cooling for prevention of spinal cord ischemic complications after thoracoabdominal aortic surgery. Semin Thorac Cardiovasc Surg. 2003;15:345–352.
18. Cambria RP, Davison JK. Regional hypothermia with epidural cooling for prevention of spinal cord ischemic complications after thoracoabdominal aortic surgery. Semin Thorac Cardiovasc Surg. 2000;13:315–324
19. Westergren H, Farooque M, Olsson Y et al. Spinal cord blood flow charges following systemic hypothermia and spinal cord compression injury: An experimental study in the rat using laser-Doppler flowmetry. Spinal Cord. 2001;39:74–84.
20. Marsala M, Vanicky I, Galik J et al. Panmyelic epidural cooling protects against ischemic spinal cord damage. J Surg Res. 1993;55:21–31.
21. Dimar JR, Shields CB, Zhang YP et al. The role of directly applied hypothermia in spinal cord injury. Spine. 2000;25:2294–2302.
22. Downey JA, Miller JM, Darling RC. Thermoregulatory responses to deep and superficial cooling in spinal man. J. Appl Physiol. 1969;27:209–212.
23. Botel U, Glaser E, Niedeggen A. The surgical treatment of acute spinal paralysed patients. Spinal Cord. 1997;35:420–428.
24. Dietrich WD, Atkins CM, Bramlett HM. Protection in animal models of brain and spinal cord injury with mild to moderate hypothermia. J Neurotrauma. 2009;26:301–312.
25. Marion D, Bullock MR. Current and future role of therapeutic hypothermia. J. Neurotrauma. 2009;26:455–467.
26. Martirosyan NL, Patel AA, Carotenuto A, et al. The role of therapeutic hypothermia in the management of acute spinal cord injury. Clin Neurol Neurosurg. 2017;154:79-88.
27. Ahmad FU, Wang MY, Levi AD. Hypothermia for acute spinal cord injury—areview. World Neurosurg. 2014;82(1-2):207-14.
28. Calver P, Braungardt T, Kupchik N, Jensen A, Cutler C. The big chill: improving the odds after cardiac arrest. RN. 2005 May;68(5):58-62; quiz 63.Review. PubMed PMID: 15931934.
29. Schwab S, Georgiadis D, Berrouschot J, et al. Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke. 2001;32(9):2033–2035.
30. Schubert A. Side effects of mild hypothermia. J Neurosurg Anesthesiol. 1995;7(2):139–147.
31. Dietrich WD, Busto R, Alonso O et al. Intraischemic but not postischemic brain hypothermia protects chronically following global forebrain ischemia in rats. J Cereb Blood Flow Metab. 1993;13(4):541–549
32. Colbourne F, Corbett D. Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection. J Neurosci. 1995;15(11):7250–7260.
33. Lo TP, Jr, Cho KS, Garg MS, et al. Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol. 2009;514(5):433–448.
34. Hansebout RR, Kuchner EF, Romero-Sierra C. Effects of local hypothermia and of steroids upon recovery from experimental spinal cord compression injury. Surg Neurol. 1975;4(6):531–536.
35. Casas CE, Herrera LP, Prusmack C et al. Effects of epidural hypothermic saline infusion on locomotor outcome and tissue preservation after moderate thoracic spinal cord contusion in rats. J Neurosurg Spine. 2005;2(3):308–318
36. Lyeth BG, Jiang JY, Liu S. Behavioral protection by moderate hypothermia initiated after experimental traumatic brain injury. J Neurotrauma. 1993;10(1):57–64
37. Koizumi H, Povlishock JT. Posttraumatic hypothermia in the treatment of axonal damage in an animal model of traumatic axonal injury. J Neurosurg. 1998;89(2):303–309.
38. Marion DW, White MJ. Treatment of experimental brain injury with moderate hypothermia and 21-aminosteroids. J Neurotrauma. 1996;13(3):139–147.
39. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. III. Prophylactic hypothermia. J Neurotrauma. 2007;24(Suppl 1):S21–25
40. Aibiki M, Maekawa S, Yokono S. Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans. Crit Care Med. 2000;28(12):3902–3906.
41. Qiu W, Zhang Y, Sheng H, et al. Effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy. J Crit Care. 2007;22(3):229–235
42. Dong H, Moody-Corbett F, Colbourne F, etal. Electrophysiological properties of CA1 neurons protected by postischemic hypothermia in gerbils. Stroke. 2001;32(3):788–795.
43. Zhao H, Wang JQ, Shimohata T, et al. Conditions of protection by hypothermia and effects on apoptotic pathways in a rat model of permanent middle cerebral artery occlusion. J Neurosurg. 2007;107(3):636–641.
44. Zhang Y, Lv Y, Ji W, et al. Therapeutic hypothermiaeffectively reduces elevated extracellular ascorbate concentrations caused byacute spinal cord injury. Artif Cells NanomedBiotechnol. 2019 Dec;47(1):22-29.doi: 10.1080/21691401.2018.1541136. Epub 2018 Dec 11. PubMed PMID: 30526134
45. Seupaul RA, Wilbur LG. Evidence-based emergency medicine. Does therapeutic hypothermia benefit survivors of cardiac arrest? Ann Emerg Med. 2011;58(3):282–283
46. Lotocki G, de Rivero Vaccari JP, Perez ER, et al. Alterations in blood-brain barrier permeability to large and small molecules and leukocyte accumulation after traumatic brain injury: effects of post-traumatic hypothermia. J Neurotrauma. 2009;26(7):1123–1134.
47. Morino T, Ogata T, Takeba J, et al. Microglia inhibition is a target of mild hypothermic treatment after the spinal cord injury. Spinal Cord. 2008;46(6):425–431
48. Small DL, Morley P, Buchan AM. Biology of ischemic cerebral cell death. Prog Cardiovasc Dis. 1999;42(3):185–207
49. Milde LN. Clinical use of mild hypothermia for brain protection: a dream revisited. J NeurosurgAnesthesiol. 1992;4(3):211–215.
50. Xu L, Yenari MA, Steinberg GK, et al. Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab. 2002;22(1):21–28
51. Wang J, Pearse DD. Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions. Int J Mol Sci. 2015;16(8):16848–16879
52. Sun YJ, Zhang ZY, Fan B, Li GY. Neuroprotection by Therapeutic Hypothermia. Front Neurosci. 2019 Jun 11;13:586. doi: 10.3389/fnins.2019.00586. eCollection2019. Review. PubMed PMID: 31244597; PubMed Central PMCID: PMC6579927.
53. Wang L, Jiang F, Li Q, He X, Ma J. Mild hypothermia combined with neural stem cell transplantation for hypoxic-ischemic encephalopathy: neuroprotective effects of combined therapy. Neural Regen Res. 2014 Oct 1;9(19):1745-52. doi:10.4103/1673-5374.143417.
54. Vishwakarma SK, Bardia A, Chandrakala L, et al. Enhanced neuroprotective effect of mild-hypothermia with VPA against ethanol-mediated neuronal injury. Tissue Cell. 2017 Dec;49(6):638-647. doi: 10.1016/j.tice.2017.09.004. Epub 2017 Sep 14. PubMed PMID: 28947065.
55. Barks JD, Liu YQ, Shangguan Y, Silverstein FS. Phenobarbital augments hypothermic neuroprotection. Pediatr Res. 2010 May;67(5):532-7. doi: 10.1203/PDR.0b013e3181d4ff4d. PubMed PMID: 20098339; PubMed Central PMCID: PMC2906127.
56. Gao XY, Huang JO, Hu YF, et al. Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury. Sci Rep. 2014 Nov 18;4:7091. doi: 10.1038/srep07091. Erratum in: Sci Rep.2015;5:12195. PubMed PMID: 25404538; PubMed Central PMCID: PMC4665348.
57. Tu Y, Miao XM, Yi TL, et al. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury. Neural Regen Res. 2016 Jun;11(6):931-6. doi:10.4103/1673-5374.184491. PubMed PMID: 27482221; PubMed Central PMCID: PMC4962590.
58. Zhu H, Meloni BP, Bojarski C, et al. Post-ischemic modest hypothermia (35 degrees C) combined with intravenous magnesium is more effective at reducing CA1 neuronal death than either treatment used alone following global cerebral ischemia in rats. Exp Neurol. 2005 Jun;193(2):361-8. PubMed PMID:15869938.
59. Ma D, Hossain M, Chow A, Arshad M, et al. Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia. Ann Neurol. 2005 Aug;58(2):182-93. PubMed PMID: 16049939.
Published
2021-08-20
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