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Hypothermia to Identify Therapeutic Targets for Stroke Treatment

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Translational Stroke Research

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

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Abstract

Hypothermia has emerged as a viable neuroprotectant at the clinical level. The reasons for its protective effect are likely due to its ability to affect multiple facets of ischemic brain injury. While at times difficult to implement in humans due to various comorbidities, hypothermia can also be viewed as a tool by which neuroprotective targets may be identified. In this review, we discuss optimal conditions for therapeutic hypothermia, as evidenced by laboratory studies, as well as many of the effects of cooling on several cell death and cell survival pathways. The collective scientific literature indicates that temperature need only be decreased by a few degrees in order to confer protection, but early cooling and cooling of somewhat long duration (12–24 h) seem to be the more critical factors that determine success. Hypothermia seems to halt many damaging processes that lead to brain tissue injury, while upregulating factors that aid in its recovery. However, it should be noted that not all forms of brain injury benefit from therapeutic cooling. While global and focal cerebral ischemia appears to benefit from hypothermia, it is less clear whether brain hemorrhage responds in the same way. Thus, the laboratory literature also emphasizes the importance of careful preclinical studies prior to applying such concepts to humans.

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References

  1. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557–63.

    Article  PubMed  Google Scholar 

  2. HACA. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56.

    Article  Google Scholar 

  3. Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365:663–70.

    PubMed  Google Scholar 

  4. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–84.

    Article  PubMed  CAS  Google Scholar 

  5. Azzopardi D, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349–58.

    Article  PubMed  CAS  Google Scholar 

  6. Simbruner G, Mittal RA, Rohlmann F, Muche R. Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics. 2010;126:e771–8.

    Article  PubMed  Google Scholar 

  7. Schwab S, Schwarz S, Spranger M, et al. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke. 1998;29:2461–6.

    Article  PubMed  CAS  Google Scholar 

  8. De Georgia MA, Krieger DW, Abou-Chebl A, et al. Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology. 2004;63:312–7.

    Article  PubMed  Google Scholar 

  9. Lyden PD, Allgren RL, Ng K, et al. Intravascular cooling in the treatment of stroke (ICTuS): early clinical experience. J Stroke Cerebrovasc Dis. 2005;14:107–14.

    Article  PubMed  Google Scholar 

  10. Hemmen TM, Raman R, Guluma KZ, et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010;41:2265–70.

    Article  PubMed  Google Scholar 

  11. Schwab S, Georgiadis D, Berrouschot J, et al. Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke. 2001;32:2033–5.

    Article  PubMed  CAS  Google Scholar 

  12. Lyden PD, Krieger D, Yenari M, Dietrich WD. Therapeutic hypothermia for acute stroke. Int J Stroke. 2006;1:9–19.

    Article  PubMed  Google Scholar 

  13. Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med. 2009;37:1101–20.

    Article  PubMed  Google Scholar 

  14. Busto R, Dietrich WD, Globus MY, Ginsberg MD. The importance of brain temperature in cerebral ischemic injury. Stroke. 1989;20:1113–4.

    Article  PubMed  CAS  Google Scholar 

  15. Busto R, Dietrich WD, Globus MY, et al. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab. 1987;7:729–38.

    Article  PubMed  CAS  Google Scholar 

  16. van der Worp HB, Macleod MR, Kollmar R. Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials? J Cereb Blood Flow Metab. 2010;30:1079–93.

    Article  PubMed  Google Scholar 

  17. Maier CM, Ahern K, Cheng ML, et al. Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and inflammation. Stroke. 1998;29:2171–80.

    Article  PubMed  CAS  Google Scholar 

  18. Huh PW, Belayev L, Zhao W, et al. Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia. J Neurosurg. 2000;92:91–9.

    Article  PubMed  CAS  Google Scholar 

  19. Kollmar R, Blank T, Han JL, et al. Different degrees of hypothermia after experimental stroke: short- and long-term outcome. Stroke. 2007;38:1585–9.

    Article  PubMed  Google Scholar 

  20. Georgiadis D, Schwarz S, Kollmar R, Schwab S. Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke. 2001;32:2550–3.

    Article  PubMed  CAS  Google Scholar 

  21. Krieger DW, De Georgia MA, Abou-Chebl A, et al. Cooling for acute ischemic brain damage (cool aid): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke. 2001;32:1847–54.

    Article  PubMed  CAS  Google Scholar 

  22. Jacobs S, Hunt R, Tarnow-Mordi W, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2007:CD003311.

    Google Scholar 

  23. Hutchison JS, Ward RE, Lacroix J, et al. Hypothermia therapy after traumatic brain injury in children. N Engl J Med. 2008;358:2447–56.

    Article  PubMed  CAS  Google Scholar 

  24. Peterson K, Carson S, Carney N. Hypothermia treatment for traumatic brain injury: a systematic review and meta-analysis. J Neurotrauma. 2008;25:62–71.

    Article  PubMed  Google Scholar 

  25. Tokutomi T, Miyagi T, Takeuchi Y, et al. Effect of 35 degrees C hypothermia on intracranial pressure and clinical outcome in patients with severe traumatic brain injury. J Trauma. 2009;66:166–73.

    Article  PubMed  Google Scholar 

  26. Kammersgaard LP, Rasmussen BH, Jorgensen HS, et al. Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: a case-control study: the Copenhagen Stroke Study. Stroke. 2000;31:2251–6.

    Article  PubMed  CAS  Google Scholar 

  27. Krieger DW, Yenari MA. Therapeutic hypothermia for acute ischemic stroke: what do laboratory studies teach us? Stroke. 2004;35:1482–9.

    Article  PubMed  Google Scholar 

  28. Clark DL, Penner M, Orellana-Jordan IM, Colbourne F. Comparison of 12, 24 and 48 h of systemic hypothermia on outcome after permanent focal ischemia in rat. Exp Neurol. 2008;212:386–92.

    Article  PubMed  Google Scholar 

  29. Colbourne F, Corbett D. Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. Brain Res. 1994;654:265–72.

    Article  PubMed  CAS  Google Scholar 

  30. Colbourne F, Corbett D, Zhao Z, et al. Prolonged but delayed postischemic hypothermia: a long-term outcome study in the rat middle cerebral artery occlusion model. J Cereb Blood Flow Metab. 2000;20:1702–8.

    Article  PubMed  CAS  Google Scholar 

  31. van der Worp HB, Sena ES, Donnan GA, et al. Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis. Brain. 2007;130:3063–74.

    Article  PubMed  Google Scholar 

  32. Zhang ZG, Chopp M, Chen H. Duration dependent post-ischemic hypothermia alleviates cortical damage after transient middle cerebral artery occlusion in the rat. J Neurol Sci. 1993;117:240–4.

    Article  PubMed  CAS  Google Scholar 

  33. Carroll M, Beek O. Protection against hippocampal CA1 cell loss by post-ischemic hypothermia is dependent on delay of initiation and duration. Metab Brain Dis. 1992;7:45–50.

    Article  PubMed  CAS  Google Scholar 

  34. 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;13:541–9.

    Article  PubMed  CAS  Google Scholar 

  35. Shuaib A, Waqar T, Wishart T, Kanthan R. Post-ischemic therapy with CGS-19755 (alone or in combination with hypothermia) in gerbils. Neurosci Lett. 1995;191:87–90.

    Article  PubMed  CAS  Google Scholar 

  36. Colbourne F, Corbett D. Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection. J Neurosci. 1995;15:7250–60.

    PubMed  CAS  Google Scholar 

  37. Colbourne F, Li H, Buchan AM. Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats. J Cereb Blood Flow Metab. 1999;19:742–9.

    Article  PubMed  CAS  Google Scholar 

  38. Olsen TS, Weber UJ, Kammersgaard LP. Therapeutic hypothermia for acute stroke. Lancet Neurol. 2003;2:410–6.

    Article  PubMed  Google Scholar 

  39. Shackelford RT, Hegedus SA. Factors affecting cerebral blood flow—experimental review: sympathectomy, hypothermia, CO2 inhalation and pavarine. Ann Surg. 1966;163:771–7.

    Article  PubMed  CAS  Google Scholar 

  40. Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in mammalian central nervous system. J Cereb Blood Flow Metab. 2003;23:513–30.

    Article  PubMed  CAS  Google Scholar 

  41. Hagerdal M, Harp J, Nilsson L, Siesjo BK. The effect of induced hypothermia upon oxygen consumption in the rat brain. J Neurochem. 1975;24:311–6.

    Article  PubMed  CAS  Google Scholar 

  42. Hagerdal M, Harp J, Siesjo BK. Effect of hypothermia upon organic phosphates, glycolytic metabolites, citric acid cycle intermediates and associated amino acids in rat cerebral cortex. J Neurochem. 1975;24:743–8.

    PubMed  CAS  Google Scholar 

  43. Ehrlich MP, McCullough JN, Zhang N, et al. Effect of hypothermia on cerebral blood flow and metabolism in the pig. Ann Thorac Surg. 2002;73:191–7.

    Article  PubMed  Google Scholar 

  44. Yenari M, Wijman C, Steinberg G. Effects of hypothermia on cerebral metabolism, blood flow, and autoregulation. New York: Marcel Dekker; 2004. p. 141–78.

    Google Scholar 

  45. Busto R, Globus MY, Dietrich WD, et al. Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke. 1989;20:904–10.

    Article  PubMed  CAS  Google Scholar 

  46. Matsumoto M, Scheller MS, Zornow MH, Strnat MA. Effect of S-emopamil, nimodipine, and mild hypothermia on hippocampal glutamate concentrations after repeated cerebral ischemia in rabbits. Stroke. 1993;24:1228–34.

    Article  PubMed  CAS  Google Scholar 

  47. Mitani A, Kataoka K. Critical levels of extracellular glutamate mediating gerbil hippocampal delayed neuronal death during hypothermia: brain microdialysis study. Neuroscience. 1991;42:661–70.

    Article  PubMed  CAS  Google Scholar 

  48. Young RS, Zalneraitis EL, Dooling EC. Neurological outcome in cold water drowning. JAMA. 1980;244:1233–5.

    Article  PubMed  CAS  Google Scholar 

  49. Colbourne F, Grooms SY, Zukin RS, et al. Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia. Proc Natl Acad Sci U S A. 2003;100:2906–10.

    Article  PubMed  CAS  Google Scholar 

  50. Hu BR, Kamme F, Wieloch T. Alterations of Ca2+/calmodulin-dependent protein kinase II and its messenger RNA in the rat hippocampus following normo- and hypothermic ischemia. Neuroscience. 1995;68:1003–16.

    Article  PubMed  CAS  Google Scholar 

  51. Takata T, Nabetani M, Okada Y. Effects of hypothermia on the neuronal activity, [Ca2+]i accumulation and ATP levels during oxygen and/or glucose deprivation in hippocampal slices of guinea pigs. Neurosci Lett. 1997;227:41–4.

    Article  PubMed  CAS  Google Scholar 

  52. Taylor CP, Burke SP, Weber ML. Hippocampal slices: glutamate overflow and cellular damage from ischemia are reduced by sodium-channel blockade. J Neurosci Methods. 1995;59:121–8.

    Article  PubMed  CAS  Google Scholar 

  53. Kim JY, Kim N, Chang W, Yenari MA. Mild hypothermia suppresses calcium sensing receptor (CaSR) induction following forebrain ischemia while increasing GABA-B receptor1 (GABA-B-R1) expression. Transl Stroke Res. 2011;2(2):195–201.

    Article  PubMed  CAS  Google Scholar 

  54. Liu L, Yenari MA. Therapeutic hypothermia: neuroprotective mechanisms. Front Biosci. 2007;12:816–25.

    Article  PubMed  CAS  Google Scholar 

  55. Inamasu J, Suga S, Sato S, et al. Intra-ischemic hypothermia attenuates intercellular adhesion molecule-1 (ICAM-1) and migration of neutrophil. Neurol Res. 2001;23:105–11.

    Article  PubMed  CAS  Google Scholar 

  56. Kawai N, Okauchi M, Morisaki K, Nagao S. Effects of delayed intraischemic and postischemic hypothermia on a focal model of transient cerebral ischemia in rats. Stroke. 2000;31:1982–9. discussion 1989.

    Article  PubMed  CAS  Google Scholar 

  57. Wang GJ, Deng HY, Maier CM, et al. Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke. Neuroscience. 2002;114:1081–90.

    Article  PubMed  CAS  Google Scholar 

  58. Han HS, Qiao Y, Karabiyikoglu M, et al. Influence of mild hypothermia on inducible nitric oxide synthase expression and reactive nitrogen production in experimental stroke and inflammation. J Neurosci. 2002;22:3921–8.

    PubMed  CAS  Google Scholar 

  59. Yenari MA, Han HS. Influence of hypothermia on post-ischemic inflammation: role of nuclear factor kappa B (NFkappaB). Neurochem Int. 2006;49:164–9.

    Article  PubMed  CAS  Google Scholar 

  60. Webster CM, Kelly S, Koike MA, et al. Inflammation and NFkappaB activation is decreased by hypothermia following global cerebral ischemia. Neurobiol Dis. 2009;33:301–12.

    Article  PubMed  CAS  Google Scholar 

  61. Dietrich WD, Busto R, Halley M, Valdes I. The importance of brain temperature in alterations of the blood–brain barrier following cerebral ischemia. J Neuropathol Exp Neurol. 1990;49:486–97.

    Article  PubMed  CAS  Google Scholar 

  62. Burk J, Burggraf D, Vosko M, et al. Protection of cerebral microvasculature after moderate hypothermia following experimental focal cerebral ischemia in mice. Brain Res. 2008;1226:248–55.

    Article  PubMed  CAS  Google Scholar 

  63. Hamann GF, Burggraf D, Martens HK, et al. Mild to moderate hypothermia prevents microvascular basal lamina antigen loss in experimental focal cerebral ischemia. Stroke. 2004;35:764–9.

    Article  PubMed  Google Scholar 

  64. Lee JE, Yoon YJ, Moseley ME, Yenari MA. Reduction in levels of matrix metalloproteinases and increased expression of tissue inhibitor of metalloproteinase-2 in response to mild hypothermia therapy in experimental stroke. J Neurosurg. 2005;103:289–97.

    Article  PubMed  CAS  Google Scholar 

  65. Truettner JS, Alonso OF, Dalton Dietrich W. Influence of therapeutic hypothermia on matrix metalloproteinase activity after traumatic brain injury in rats. J Cereb Blood Flow Metab. 2005;25:1505–16.

    Article  PubMed  CAS  Google Scholar 

  66. Wagner S, Nagel S, Kluge B, et al. Topographically graded postischemic presence of metalloproteinases is inhibited by hypothermia. Brain Res. 2003;984:63–75.

    Article  PubMed  CAS  Google Scholar 

  67. Globus MY, Busto R, Lin B, et al. Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. J Neurochem. 1995;65:1250–6.

    Article  PubMed  CAS  Google Scholar 

  68. Maier CM, Sun GH, Cheng D, et al. Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia. Neurobiol Dis. 2002;11:28–42.

    Article  PubMed  CAS  Google Scholar 

  69. Yenari MA. Heat shock proteins and neuroprotection. Adv Exp Med Biol. 2002;513:281–99.

    Article  PubMed  CAS  Google Scholar 

  70. Yenari M, Kitagawa K, Lyden P, Perez-Pinzon M. Metabolic downregulation: a key to successful neuroprotection? Stroke. 2008;39:2910–7.

    Article  PubMed  CAS  Google Scholar 

  71. Han HS, Yenari MA. Effect of gene expression by therapeutic hypothermia in cerebral ischemia. Future Neurol. 2007;2:435–40.

    Article  CAS  Google Scholar 

  72. Hemmen TM, Lyden PD. Induced hypothermia for acute stroke. Stroke. 2007;38:794–9.

    Article  PubMed  Google Scholar 

  73. Behringer W. Global brain ischemia: animal studies. In: Tisherman SA, Sterz F, editors. Therapeutic hypothermia. New York: Springer; 2005. p. 1–10.

    Chapter  Google Scholar 

  74. Laptook AR. Use of therapeutic hypothermia for term infants with hypoxic-ischemic encephalopathy. Pediatr Clin North Am. 2009;56:601–16.

    Article  PubMed  Google Scholar 

  75. Tang XN, Yenari MA. Hypothermia as a cytoprotective strategy in ischemic tissue injury. Ageing Res Rev. 2010;9:61–8.

    Article  PubMed  Google Scholar 

  76. Fingas M, Clark DL, Colbourne F. The effects of selective brain hypothermia on intracerebral hemorrhage in rats. Exp Neurol. 2007;208:277–84.

    Article  PubMed  Google Scholar 

  77. MacLellan CL, Davies LM, Fingas MS, Colbourne F. The influence of hypothermia on outcome after intracerebral hemorrhage in rats. Stroke. 2006;37:1266–70.

    Article  PubMed  Google Scholar 

  78. Kawanishi M, Kawai N, Nakamura T, et al. Effect of delayed mild brain hypothermia on edema formation after intracerebral hemorrhage in rats. J Stroke Cerebrovasc Dis. 2008;17:187–95.

    Article  PubMed  Google Scholar 

  79. MacLellan CL, Girgis J, Colbourne F. Delayed onset of prolonged hypothermia improves outcome after intracerebral hemorrhage in rats. J Cereb Blood Flow Metab. 2004;24:432–40.

    Article  PubMed  Google Scholar 

  80. Kollmar R, Staykov D, Dorfler A, et al. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2010;41:1684–9.

    Article  PubMed  Google Scholar 

  81. Torok E, Klopotowski M, Trabold R, et al. Mild hypothermia (33 degrees C) reduces intracranial hypertension and improves functional outcome after subarachnoid hemorrhage in rats. Neurosurgery. 2009;65:352–9.

    Article  PubMed  Google Scholar 

  82. Schubert GA, Poli S, Schilling L, et al. Hypothermia reduces cytotoxic edema and metabolic alterations during the acute phase of massive SAH: a diffusion-weighted imaging and spectroscopy study in rats. J Neurotrauma. 2008;25:841–52.

    Article  PubMed  Google Scholar 

  83. Kawamura Y, Yamada K, Masago A, et al. Hypothermia modulates induction of hsp70 and c-jun mRNA in the rat brain after subarachnoid hemorrhage. J Neurotrauma. 2000;17:243–50.

    Article  PubMed  CAS  Google Scholar 

  84. Muroi C, Frei K, El Beltagy M, et al. Combined therapeutic hypothermia and barbiturate coma reduces interleukin-6 in the cerebrospinal fluid after aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol. 2008;20:193–8.

    Article  PubMed  Google Scholar 

  85. Todd MM, Hindman BJ, Clarke WR, Torner JC. Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med. 2005;352:135–45.

    Article  PubMed  CAS  Google Scholar 

  86. Seule MA, Muroi C, Mink S, et al. Therapeutic hypothermia in patients with aneurysmal subarachnoid hemorrhage, refractory intracranial hypertension, or cerebral vasospasm. Neurosurgery. 2009;64:86–92. discussion 83–92.

    Article  PubMed  Google Scholar 

  87. Fernandez A, Schmidt JM, Claassen J, et al. Fever after subarachnoid hemorrhage: risk factors and impact on outcome. Neurology. 2007;68:1013–9.

    Article  PubMed  CAS  Google Scholar 

  88. Proust F, Hannequin D, Langlois O, et al. Causes of morbidity and mortality after ruptured aneurysm surgery in a series of 230 patients. The importance of control angiography. Stroke. 1995;26:1553–7.

    Article  PubMed  CAS  Google Scholar 

  89. Elewa HF, Hilali H, Hess DC, et al. Minocycline for short-term neuroprotection. Pharmacotherapy. 2006;26:515–21.

    Article  PubMed  CAS  Google Scholar 

  90. Lampl Y, Boaz M, Gilad R, et al. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007;69:1404–10.

    Article  PubMed  CAS  Google Scholar 

  91. Fagan SC, Waller JL, Nichols FT, et al. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010;41:2283–7.

    Article  PubMed  CAS  Google Scholar 

  92. Kobayashi MS, Asai S, Ishikawa K, et al. Global profiling of influence of intra-ischemic brain temperature on gene expression in rat brain. Brain Res Rev. 2008;58:171–91.

    Article  PubMed  CAS  Google Scholar 

  93. Kelly S, Yenari MA. Neuroprotection: heat shock proteins. Curr Med Res Opin. 2002;18 Suppl 2:s55–60.

    Article  PubMed  Google Scholar 

  94. Kumar K, Wu X, Evans AT, Marcoux F. The effect of hypothermia on induction of heat shock protein (HSP)-72 in ischemic brain. Metab Brain Dis. 1995;10:283–91.

    Article  PubMed  CAS  Google Scholar 

  95. Gordon CJ, McMahon B, Richelson E, et al. Neurotensin analog NT77 induces regulated hypothermia in the rat. Life Sci. 2003;73:2611–23.

    Article  PubMed  CAS  Google Scholar 

  96. Katz LM, Young A, Frank JE, et al. Neurotensin-induced hypothermia improves neurologic outcome after hypoxic-ischemia. Crit Care Med. 2004;32:806–10.

    Article  PubMed  Google Scholar 

  97. Tyler-McMahon BM, Stewart JA, Farinas F, et al. Highly potent neurotensin analog that causes hypothermia and antinociception. Eur J Pharmacol. 2000;390:107–11.

    Article  PubMed  CAS  Google Scholar 

  98. Scanlan TS, Suchland KL, Hart ME, et al. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med. 2004;10:638–42.

    Article  PubMed  CAS  Google Scholar 

  99. Blackstone E, Roth MB. Suspended animation-like state protects mice from lethal hypoxia. Shock. 2007;27:370–2.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Department of Veterans Affairs, grants to MAY from the NIH R01 NS 40156, P50 NS014543, Department of Veterans Affairs Merit Review Award I01BX007080, and the Department of Defense DAMD17-03-1-0532. Grants were administered by the Northern California Institute for Research and Education, and supported by resources of the San Francisco Veterans Affairs Medical Center.

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  1. Department of Neurology, University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA, 94121, USA

    Masaaki Hokari MD, PhD & Midori A. Yenari MD

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  1. Masaaki Hokari MD, PhD
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  2. Midori A. Yenari MD
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Correspondence to Midori A. Yenari MD .

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  1. , Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, 90048, California, USA

    Paul A. Lapchak

  2. Loma Linda University, 11234 Anderson Street, Room 2562B, Loma Linda, 92354, California, USA

    John H. Zhang

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Hokari, M., Yenari, M.A. (2012). Hypothermia to Identify Therapeutic Targets for Stroke Treatment. In: Lapchak, P., Zhang, J. (eds) Translational Stroke Research. Springer Series in Translational Stroke Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9530-8_15

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