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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Therapeutic Hypothermia and Neuroprotection in Acute Neurological Disease

Author(s): Kota Kurisu, Jong Youl Kim, Jesung You and Midori A. Yenari*

Volume 26, Issue 29, 2019

Page: [5430 - 5455] Pages: 26

DOI: 10.2174/0929867326666190506124836

Price: $65


Therapeutic hypothermia has consistently been shown to be a robust neuroprotectant in many labs studying different models of neurological disease. Although this therapy has shown great promise, there are still challenges at the clinical level that limit the ability to apply this routinely to each pathological condition. In order to overcome issues involved in hypothermia therapy, understanding of this attractive therapy is needed. We review methodological concerns surrounding therapeutic hypothermia, introduce the current status of therapeutic cooling in various acute brain insults, and review the literature surrounding the many underlying molecular mechanisms of hypothermic neuroprotection. Because recent work has shown that body temperature can be safely lowered using pharmacological approaches, this method may be an especially attractive option for many clinical applications. Since hypothermia can affect multiple aspects of brain pathophysiology, therapeutic hypothermia could also be considered a neuroprotection model in basic research, which would be used to identify potential therapeutic targets. We discuss how research in this area carries the potential to improve outcome from various acute neurological disorders.

Keywords: Hypothermia, pharmacology induced hypothermia, stroke, traumatic brain injury, cardiac arrest, hypoxic- ischemic encephalopathy.

Kurisu, K.; Yenari, M.A. Therapeutic hypothermia for ischemic stroke; Pathophysiology and future promise. Neuropharmacology, 2018. 134(pt. B), 302-309.
[PMID: 28830757]
Yenari, M.A.; Han, H.S. Neuroprotective mechanisms of hypothermia in brain ischaemia. Nat. Rev. Neurosci., 2012, 13(4), 267-278.
[] [PMID: 22353781]
Bernard, S.A.; Gray, T.W.; Buist, M.D.; Jones, B.M.; Silvester, W.; Gutteridge, G.; Smith, K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N. Engl. J. Med., 2002, 346(8), 557-563.
[] [PMID: 11856794]
Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N. Engl. J. Med., 2002, 346(8), 549-556.
[] [PMID: 11856793]
Azzopardi, D.V.; Strohm, B.; Edwards, A.D.; Dyet, L.; Halliday, H.L.; Juszczak, E.; Kapellou, O.; Levene, M.; Marlow, N.; Porter, E.; Thoresen, M.; Whitelaw, A.; Brocklehurst, P.; Group, T.S. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N. Engl. J. Med., 2009, 361(14), 1349-1358.
[] [PMID: 19797281]
Gluckman, P.D.; Wyatt, J.S.; Azzopardi, D.; Ballard, R.; Edwards, A.D.; Ferriero, D.M.; Polin, R.A.; Robertson, C.M.; Thoresen, M.; Whitelaw, A.; Gunn, A.J. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: Multicentre randomised trial. Lancet, 2005, 365(9460), 663-670.
[] [PMID: 15721471]
Shankaran, S.; Laptook, A.R.; Ehrenkranz, R.A.; Tyson, J.E.; McDonald, S.A.; Donovan, E.F.; Fanaroff, A.A.; Poole, W.K.; Wright, L.L.; Higgins, R.D.; Finer, N.N.; Carlo, W.A.; Duara, S.; Oh, W.; Cotten, C.M.; Stevenson, D.K.; Stoll, B.J.; Lemons, J.A.; Guillet, R.; Jobe, A.H. National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N. Engl. J. Med., 2005, 353(15), 1574-1584.
[] [PMID: 16221780]
van der Worp, H.B.; Macleod, M.R.; Bath, P.M.; Demotes, J.; Durand-Zaleski, I.; Gebhardt, B.; Gluud, C.; Kollmar, R.; Krieger, D.W.; Lees, K.R.; Molina, C.; Montaner, J.; Roine, R.O.; Petersson, J.; Staykov, D.; Szabo, I.; Wardlaw, J.M.; Schwab, S. EuroHYP-1 investigators. 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(5), 642-645.
[] [PMID: 24828363]
Lyden, P.; Hemmen, T.; Grotta, J.; Rapp, K.; Ernstrom, K.; Rzesiewicz, T.; Parker, S.; Concha, M.; Hussain, S.; Agarwal, S.; Meyer, B.; Jurf, J.; Altafullah, I.; Raman, R. Collaborators. Results of the ICTUS 2 trial (intravascular cooling in the treatment of stroke 2). Stroke, 2016, 47(12), 2888-2895.
[] [PMID: 27834742]
Chiu, A.W.; Hinson, H.E. Future directions for hypothermia following severe traumatic brian injury. Semin. Respir. Crit. Care Med., 2017, 38(6), 768-774.
[] [PMID: 29262434]
Watson, H.I.; Shepherd, A.A.; Rhodes, J.K.J.; Andrews, P.J.D. Revisited: A systematic review of therapeutic hypothermia for adult patients following traumatic brain injury. Crit. Care Med., 2018, 46(6), 972-979.
[] [PMID: 29601315]
Meinert, E.; Bell, M.J.; Buttram, S.; Kochanek, P.M.; Balasubramani, G.K.; Wisniewski, S.R.; Adelson, P.D. Pediatric Traumatic Brain Injury Consortium. Hypothermia Investigators. Hypothermia I: Initiating nutritional support before 72 hours is associated with favorable outcome after severe traumatic brain injury in children: A secondary analysis of a randomized, controlled trial of therapeutic hypothermia. Pediatr. Crit. Care Med., 2018, 19(4), 345-352.
[] [PMID: 29370008]
Davies, A.R. Hypothermia improves outcome from traumatic brain injury. Crit. Care Resusc., 2005, 7(3), 238-243.
[PMID: 16545052]
Hong, J.M.; Lee, J.S.; Song, H.J.; Jeong, H.S.; Choi, H.A.; Lee, K. Therapeutic hypothermia after recanalization in patients with acute ischemic stroke. Stroke, 2014, 45(1), 134-140.
[] [PMID: 24203846]
Hwang, Y.H.; Jeon, J.S.; Kim, Y.W.; Kang, D.H.; Kim, Y.S.; Liebeskind, D.S. Impact of immediate post-reperfusion cooling on outcome in patients with acute stroke and substantial ischemic changes. J. Neurointerv. Surg., 2017, 9(1), 21-25.
[] [PMID: 26940314]
van der Worp, H.B.; Macleod, M.R.; Kollmar, R. European Stroke Research Network for Hypothermia (EuroHYP). Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials? J. Cereb. Blood Flow Metab., 2010, 30(6), 1079-1093.
[] [PMID: 20354545]
Krieger, D.W.; Yenari, M.A. Therapeutic hypothermia for acute ischemic stroke: what do laboratory studies teach us? Stroke, 2004, 35(6), 1482-1489.
[] [PMID: 15073396]
Wu, T.C.; Grotta, J.C. Hypothermia for acute ischaemic stroke. Lancet Neurol., 2013, 12(3), 275-284.
[] [PMID: 23415567]
Lyden, P.D.; Krieger, D.; Yenari, M.; Dietrich, W.D. Therapeutic hypothermia for acute stroke. Int. J. Stroke, 2006, 1(1), 9-19.
[] [PMID: 18706063]
Huh, P.W.; Belayev, L.; Zhao, W.; Koch, S.; Busto, R.; Ginsberg, M.D. Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia. J. Neurosurg., 2000, 92(1), 91-99.
[] [PMID: 10616087]
Maier, C.M.; Ahern, Kv.; Cheng, M.L.; Lee, J.E.; Yenari, M.A.; Steinberg, G.K. 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(10), 2171-2180.
[] [PMID: 9756600]
Clark, D.L.; Penner, M.; Orellana-Jordan, I.M.; Colbourne, F. Comparison of 12, 24 and 48 h of systemic hypothermia on outcome after permanent focal ischemia in rat. Exp. Neurol., 2008, 212(2), 386-392.
[] [PMID: 18538766]
Lawrence, E.J.; Dentcheva, E.; Curtis, K.M.; Roberts, V.L.; Siman, R.; Neumar, R.W. Neuroprotection with delayed initiation of prolonged hypothermia after in vitro transient global brain ischemia. Resuscitation, 2005, 64(3), 383-388.
[] [PMID: 15733770]
Colbourne, F.; Corbett, D. Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. Brain Res., 1994, 654(2), 265-272.
[] [PMID: 7987676]
Shackelford, R.T.; Hegedus, S.A. Factors affecting cerebral blood flow--experimental review: sympathectomy, hypothermia, CO2 inhalation and pavarine. Ann. Surg., 1966, 163(5), 771-777.
[] [PMID: 5930460]
Hägerdal, M.; Harp, J.; Nilsson, L.; Siesjö, B.K. The effect of induced hypothermia upon oxygen consumption in the rat brain. J. Neurochem., 1975, 24(2), 311-316.
[] [PMID: 1113108]
Lee, J.M.; Zipfel, G.J.; Choi, D.W. The changing landscape of ischaemic brain injury mechanisms. Nature, 1999, 399(6738)(Suppl.), A7-A14.
[] [PMID: 10392575]
Colbourne, F.; Li, H.; Buchan, A.M. Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats. J. Cereb. Blood Flow Metab., 1999, 19(7), 742-749.
[] [PMID: 10413028]
Liu, K.; Khan, H.; Geng, X.; Zhang, J.; Ding, Y. Pharmacological hypothermia: a potential for future stroke therapy? Neurol. Res., 2016, 38(6), 478-490.
[] [PMID: 27320243]
Rawls, S.M.; Cabassa, J.; Geller, E.B.; Adler, M.W. CB1 receptors in the preoptic anterior hypothalamus regulate WIN 55212-2 [(4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one]-induced hypothermia. J. Pharmacol. Exp. Ther., 2002, 301(3), 963-968.
[] [PMID: 12023525]
Gerdeman, G.; Lovinger, D.M. CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. J. Neurophysiol., 2001, 85(1), 468-471.
[] [PMID: 11152748]
Fernández-López, D.; Faustino, J.; Derugin, N.; Wendland, M.; Lizasoain, I.; Moro, M.A.; Vexler, Z.S. Reduced infarct size and accumulation of microglia in rats treated with WIN 55,212-2 after neonatal stroke. Neuroscience, 2012, 207, 307-315.
[] [PMID: 22285309]
Chi, O.Z.; Barsoum, S.; Grayson, J.; Hunter, C.; Liu, X.; Weiss, H.R. Effects of cannabinoid receptor agonist WIN 55,212-2 on blood-brain barrier disruption in focal cerebral ischemia in rats. Pharmacology, 2012, 89(5-6), 333-338.
[] [PMID: 22678129]
Bonfils, P.K.; Reith, J.; Hasseldam, H.; Johansen, F.F. Estimation of the hypothermic component in neuroprotection provided by cannabinoids following cerebral ischemia. Neurochem. Int., 2006, 49(5), 508-518.
[] [PMID: 16730099]
Leker, R.R.; Gai, N.; Mechoulam, R.; Ovadia, H. Drug-induced hypothermia reduces ischemic damage: effects of the cannabinoid HU-210. Stroke, 2003, 34(8), 2000-2006.
[] [PMID: 12829867]
Murakami, K.; Suzuki, M.; Suzuki, N.; Hamajo, K.; Tsukamoto, T.; Shimojo, M. Cerebroprotective effects of TAK-937, a novel cannabinoid receptor agonist, in permanent and thrombotic focal cerebral ischemia in rats: therapeutic time window, combination with t-PA and efficacy in aged rats. Brain Res., 2013, 1526, 84-93.
[] [PMID: 23791950]
Caterina, M.J.; Schumacher, M.A.; Tominaga, M.; Rosen, T.A.; Levine, J.D.; Julius, D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 1997, 389(6653), 816-824.
[] [PMID: 9349813]
Fosgerau, K.; Weber, U.J.; Gotfredsen, J.W.; Jayatissa, M.; Buus, C.; Kristensen, N.B.; Vestergaard, M.; Teschendorf, P.; Schneider, A.; Hansen, P.; Raunsø, J.; Køber, L.; Torp-Pedersen, C.; Videbaek, C. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. BMC Cardiovasc. Disord., 2010, 10, 51.
[] [PMID: 20932337]
Baker, A.K.; Meert, T.F. Functional effects of systemically administered agonists and antagonists of mu, delta, and kappa opioid receptor subtypes on body temperature in mice. J. Pharmacol. Exp. Ther., 2002, 302(3), 1253-1264.
[] [PMID: 12183687]
Torup, L.; Borsdal, J.; Sager, T. Neuroprotective effect of the neurotensin analogue JMV-449 in a mouse model of permanent middle cerebral ischaemia. Neurosci. Lett., 2003, 351(3), 173-176.
[] [PMID: 14623134]
Katz, L.M.; Wang, Y.; McMahon, B. Richelson, E Neurotensin analog nt69l induces rapid and prolonged hypothermia after hypoxic ischemia. Acad. Emerg. Med., 2001, 8, 1115-1121.
Doyle, K.P.; Suchland, K.L.; Ciesielski, T.M.; Lessov, N.S.; Grandy, D.K.; Scanlan, T.S.; Stenzel-Poore, M.P. Novel thyroxine derivatives, thyronamine and 3-iodothyronamine, induce transient hypothermia and marked neuroprotection against stroke injury. Stroke, 2007, 38(9), 2569-2576.
[] [PMID: 17690312]
Johansen, F.F.; Hasseldam, H.; Rasmussen, R.S.; Bisgaard, A.S.; Bonfils, P.K.; Poulsen, S.S.; Hansen-Schwartz, J. Drug-induced hypothermia as beneficial treatment before and after cerebral ischemia. Pathobiology, 2014, 81, 42-52.
O’Neill, M.J.; Hicks, C.A.; Ward, M.A.; Cardwell, G.P.; Reymann, J.M.; Allain, H.; Bentué-Ferrer, D. Dopamine D2 receptor agonists protect against ischaemia-induced hippocampal neurodegeneration in global cerebral ischaemia. Eur. J. Pharmacol., 1998, 352(1), 37-46.
[] [PMID: 9718265]
David, H.N.; Haelewyn, B.; Chazalviel, L.; Lecocq, M.; Degoulet, M.; Risso, J.J.; Abraini, J.H. Post-ischemic helium provides neuroprotection in rats subjected to middle cerebral artery occlusion-induced ischemia by producing hypothermia. J. Cereb. Blood Flow Metab., 2009, 29(6), 1159-1165.
[] [PMID: 19384333]
Sheng, S.P.; Lei, B.; James, M.L.; Lascola, C.D.; Venkatraman, T.N.; Jung, J.Y.; Maze, M.; Franks, N.P.; Pearlstein, R.D.; Sheng, H.; Warner, D.S. Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage. Anesthesiology, 2012, 117(6), 1262-1275.
[] [PMID: 23143806]
Zhang, F.; Wang, S.; Luo, Y.; Ji, X.; Nemoto, E.M.; Chen, J. When hypothermia meets hypotension and hyperglycemia: the diverse effects of adenosine 5′-monophosphate on cerebral ischemia in rats. J. Cereb. Blood Flow Metab., 2009, 29(5), 1022-1034.
[] [PMID: 19319149]
Zhang, M.; Li, W.; Niu, G.; Leak, R.K.; Chen, J.; Zhang, F. ATP induces mild hypothermia in rats but has a strikingly detrimental impact on focal cerebral ischemia. J. Cereb. Blood Flow Metab., 2013, 33(1), 33.
[] [PMID: 23072747]
Zhang, Z.; Zhang, L.; Ding, Y.; Han, Z.; Ji, X. Effects of therapeutic hypothermia combined with other neuroprotective strategies on ischemic stroke: Review of evidence. Aging Dis., 2018, 9(3), 507-522.
[] [PMID: 29896438]
Zhu, S.; Gao, X.; Huang, K.; Gu, Y.; Hu, Y.; Wu, Y.; Ji, Z.; Wang, Q.; Pan, S. Glibenclamide enhances the therapeutic benefits of early hypothermia after severe stroke in rats. Aging Dis., 2018, 9(4), 685-695.
[] [PMID: 30090656]
Nakayama, S.; Taguchi, N.; Isaka, Y.; Nakamura, T.; Tanaka, M. Glibenclamide and therapeutic hypothermia have comparable effect on attenuating global cerebral edema following experimental cardiac arrest. Neurocrit. Care, 2018, 29(1), 119-127.
[] [PMID: 29150777]
Huang, K.; Wang, Z.; Gu, Y.; Hu, Y.; Ji, Z.; Wang, S.; Lin, Z.; Li, X.; Xie, Z.; Pan, S. Glibenclamide is comparable to target temperature management in improving survival and neurological outcome after asphyxial cardiac arrest in rats. J. Am. Heart Assoc., 2016, 5(7), 5.
[] [PMID: 27413041]
Green, E.J.; Pazos, A.J.; Dietrich, W.D.; McCabe, P.M.; Schneiderman, N.; Lin, B.; Busto, R.; Globus, M.Y.; Ginsberg, M.D. Combined postischemic hypothermia and delayed MK-801 treatment attenuates neurobehavioral deficits associated with transient global ischemia in rats. Brain Res., 1995, 702(1-2), 145-152.
[] [PMID: 8846069]
Dietrich, W.D.; Lin, B.; Globus, M.Y.; Green, E.J.; Ginsberg, M.D.; Busto, R. Effect of delayed MK-801 (dizocilpine) treatment with or without immediate postischemic hypothermia on chronic neuronal survival after global forebrain ischemia in rats. J. Cereb. Blood Flow Metab., 1995, 15(6), 960-968.
[] [PMID: 7593357]
Alkan, T.; Kahveci, N.; Buyukuysal, L.; Korfali, E.; Ozluk, K. Neuroprotective effects of MK 801 and hypothermia used alone and in combination in hypoxic-ischemic brain injury in neonatal rats. Arch. Physiol. Biochem., 2001, 109(2), 135-144.
[] [PMID: 11780774]
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(1-2), 87-90.
[] [PMID: 7659298]
Shuaib, A.; Ijaz, S.; Mazagri, R.; Senthilsevlvan, A. CGS-19755 is neuroprotective during repetitive ischemia: This effect is significantly enhanced when combined with hypothermia. Neuroscience, 1993, 56(4), 915-920.
[] [PMID: 8284043]
Campbell, K.; Meloni, B.P.; Knuckey, N.W. Combined magnesium and mild hypothermia (35 degrees C) treatment reduces infarct volumes after permanent middle cerebral artery occlusion in the rat at 2 and 4, but not 6 h. Brain Res., 2008, 1230, 258-264.
[] [PMID: 18644354]
Song, W.; Wu, Y.M.; Ji, Z.; Ji, Y.B.; Wang, S.N.; Pan, S.Y. Intra-carotid cold magnesium sulfate infusion induces selective cerebral hypothermia and neuroprotection in rats with transient middle cerebral artery occlusion. Neurol. Sci., 2013, 34, 479-486.
Meloni, B.P.; Cross, J.L.; Brookes, L.M.; Clark, V.W.; Campbell, K.; Knuckey, N.W. FAST-Mag protocol with or without mild hypothermia (35°C) does not improve outcome after permanent MCAO in rats. Magnes. Res., 2013, 26(2), 67-73.
[PMID: 23816810]
Nito, C.; Kamiya, T.; Ueda, M.; Arii, T.; Katayama, Y. Mild hypothermia enhances the neuroprotective effects of FK506 and expands its therapeutic window following transient focal ischemia in rats. Brain Res., 2004, 1008(2), 179-185.
[] [PMID: 15145754]
Zhou, H.; Huang, S.; Sunnassee, G.; Guo, W.; Chen, J.; Guo, Y.; Tan, S. Neuroprotective effects of adjunctive treatments for acute stroke thrombolysis: a review of clinical evidence. Int. J. Neurosci., 2017, 127(11), 1036-1046.
[] [PMID: 28110588]
Nagel, S.; Su, Y.; Horstmann, S.; Heiland, S.; Gardner, H.; Koziol, J.; Martinez-Torres, F.J.; Wagner, S. Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat: effects on BBB breakdown and MMP expression in the acute and subacute phase. Brain Res., 2008, 1188, 198-206.
[] [PMID: 18031717]
Nito, C; Kamiya, T; Amemiya, S; Katoh, K; Katayama, Y Y The neuroprotective effect of a free radical scavenger and mild hypothermia following transient focal ischemia in rats. Acta neurochirurgica Supplement, 2003, 86, 199-203.
Amiri-Nikpour, M.R.; Nazarbaghi, S.; Hamdi-Holasou, M.; Rezaei, Y. An open-label evaluator-blinded clinical study of minocycline neuroprotection in ischemic stroke: gender-dependent effect. Acta Neurol. Scand., 2015, 131(1), 45-50.
[] [PMID: 25155474]
Zhu, C.; Wang, X.; Xu, F.; Qiu, L.; Cheng, X.; Simbruner, G.; Blomgren, K. Intraischemic mild hypothermia prevents neuronal cell death and tissue loss after neonatal cerebral hypoxia-ischemia. Eur. J. Neurosci., 2006, 23(2), 387-393.
[] [PMID: 16420446]
van der Worp, H.B.; Sena, E.S.; Donnan, G.A.; Howells, D.W.; Macleod, M.R. Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis. Brain, 2007, 130(Pt 12), 3063-3074.
[] [PMID: 17478443]
De Georgia, M.A.; Krieger, D.W.; Abou-Chebl, A.; Devlin, T.G.; Jauss, M.; Davis, S.M.; Koroshetz, W.J.; Rordorf, G.; Warach, S. Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology, 2004, 63(2), 312-317.
[] [PMID: 15277626]
Hemmen, T.M.; Raman, R.; Guluma, K.Z.; Meyer, B.C.; Gomes, J.A.; Cruz-Flores, S.; Wijman, C.A.; Rapp, K.S.; Grotta, J.C.; Lyden, P.D. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke, 2010, 41(10), 2265-2270.
[] [PMID: 20724711]
Kawai, N.; Kawanishi, M.; Okauchi, M.; Nagao, S. Effects of hypothermia on thrombin-induced brain edema formation. Brain Res., 2001, 895(1-2), 50-58.
[] [PMID: 11259759]
Dai, D.W.; Wang, D.S.; Li, K.S.; Mao, Y.; Zhang, L.M.; Duan, S.R.; Sheng, L. Effect of local mild hypothermia on expression of aquaporin-4 following intracerebral hemorrhage in rats. Zhonghua Yi Xue Za Zhi, 2006, 86(13), 906-910.
[PMID: 16759517]
Fingas, M.; Clark, D.L.; Colbourne, F. The effects of selective brain hypothermia on intracerebral hemorrhage in rats. Exp. Neurol., 2007, 208(2), 277-284.
[] [PMID: 17927984]
MacLellan, C.L.; Davies, L.M.; Fingas, M.S.; Colbourne, F. The influence of hypothermia on outcome after intracerebral hemorrhage in rats. Stroke, 2006, 37(5), 1266-1270.
[] [PMID: 16574928]
Melmed, K.R.; Lyden, P.D. Meta-analysis of pre-clinical trials of therapeutic hypothermia for intracerebral hemorrhage. Ther. Hypothermia Temp. Manag., 2017, 7(3), 141-146.
[] [PMID: 27906602]
Preston, E.; Webster, J. A two-hour window for hypothermic modulation of early events that impact delayed opening of the rat blood-brain barrier after ischemia. Acta Neuropathol., 2004, 108(5), 406-412.
[] [PMID: 15351891]
Yao, Z.; You, C.; He, M. Effect and feasibility of therapeutic hypothermia in patients with hemorrhagic stroke: A systematic review and meta-analysis., 2018.
Kollmar, R.; Staykov, D.; Dörfler, A.; Schellinger, P.D.; Schwab, S.; Bardutzky, J. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke, 2010, 41(8), 1684-1689.
[] [PMID: 20616317]
Rincon, F.; Friedman, D.P.; Bell, R.; Mayer, S.A.; Bray, P.F. Targeted temperature management after intracerebral hemorrhage (TTM-ICH): methodology of a prospective randomized clinical trial. Int. J. Stroke, 2014, 9(5), 646-651.
[] [PMID: 24450819]
Kollmar, R.; Juettler, E.; Huttner, H.B.; Dörfler, A.; Staykov, D.; Kallmuenzer, B.; Schmutzhard, E.; Schwab, S.; Broessner, G. Cooling in intracerebral hemorrhage (CINCH) trial: protocol of a randomized German-Austrian clinical trial. Int. J. Stroke, 2012, 7(2), 168-172.
[] [PMID: 22264371]
Török, E.; Klopotowski, M.; Trabold, R.; Thal, S.C.; Plesnila, N.; Schöller, K. Mild hypothermia (33 degrees C) reduces intracranial hypertension and improves functional outcome after subarachnoid hemorrhage in rats. Neurosurgery, 2009, 65(2), 352-359.
[] [PMID: 19625915]
Schubert, G.A.; Poli, S.; Mendelowitsch, A.; Schilling, L.; Thomé, C. Hypothermia reduces early hypoperfusion and metabolic alterations during the acute phase of massive subarachnoid hemorrhage: A laser-Doppler-flowmetry and microdialysis study in rats. J. Neurotrauma, 2008, 25(5), 539-548.
[] [PMID: 18352824]
Kawamura, Y.; Yamada, K.; Masago, A.; Katano, H.; Matsumoto, T.; Mase, M. Hypothermia modulates induction of hsp70 and c-jun mRNA in the rat brain after subarachnoid hemorrhage. J. Neurotrauma, 2000, 17(3), 243-250.
[] [PMID: 10757329]
Muroi, C.; Frei, K.; El Beltagy, M.; Cesnulis, E.; Yonekawa, Y.; Keller, E. Combined therapeutic hypothermia and barbiturate coma reduces interleukin-6 in the cerebrospinal fluid after aneurysmal subarachnoid hemorrhage. J. Neurosurg. Anesthesiol., 2008, 20(3), 193-198.
[] [PMID: 18580350]
Todd, M.M.; Hindman, B.J.; Clarke, W.R.; Torner, J.C. Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) Investigators. Mild intraoperative hypothermia during surgery for intracranial aneurysm. N. Engl. J. Med., 2005, 352(2), 135-145.
[] [PMID: 15647576]
Seule, M.A.; Muroi, C.; Mink, S.; Yonekawa, Y.; Keller, E. Therapeutic hypothermia in patients with aneurysmal subarachnoid hemorrhage, refractory intracranial hypertension, or cerebral vasospasm. Neurosurgery, 2009, 64(1), 86-92.
[] [PMID: 19050656]
Dietrich, W.D.; Bramlett, H.M. Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation. Brain Res, 2016. 1640(Pt A), 94-103.
[] [PMID: 26746342]
Andresen, M.; Gazmuri, J.T.; Marín, A.; Regueira, T.; Rovegno, M. Therapeutic hypothermia for acute brain injuries. Scand. J. Trauma Resusc. Emerg. Med., 2015, 23, 42.
[] [PMID: 26043908]
Clifton, G.L.; Jiang, J.Y.; Lyeth, B.G.; Jenkins, L.W.; Hamm, R.J.; Hayes, R.L. Marked protection by moderate hypothermia after experimental traumatic brain injury. J. Cereb. Blood Flow Metab., 1991, 11(1), 114-121.
[] [PMID: 1983995]
Bramlett, H.M.; Dietrich, W.D.; Green, E.J.; Busto, R. Chronic histopathological consequences of fluid-percussion brain injury in rats: effects of post-traumatic hypothermia. Acta Neuropathol., 1997, 93(2), 190-199.
[] [PMID: 9039468]
Dietrich, W.D.; Alonso, O.; Busto, R.; Globus, M.Y.; Ginsberg, M.D. Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat. Acta Neuropathol., 1994, 87(3), 250-258.
[] [PMID: 8009957]
Bramlett, H.M.; Dietrich, W.D. The effects of posttraumatic hypothermia on diffuse axonal injury following parasaggital fluid percussion brain injury in rats. Ther. Hypothermia Temp. Manag., 2012, 2(1), 14-23.
[] [PMID: 23420536]
Ma, M.; Matthews, B.T.; Lampe, J.W.; Meaney, D.F.; Shofer, F.S.; Neumar, R.W. Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury. Exp. Neurol., 2009, 215(1), 119-127.
[] [PMID: 18977220]
Dietrich, W.D.; Bramlett, H.M. The evidence for hypothermia as a neuroprotectant in traumatic brain injury. Neurotherapeutics, 2010, 7(1), 43-50.
[] [PMID: 20129496]
Marion, D.W.; Penrod, L.E.; Kelsey, S.F.; Obrist, W.D.; Kochanek, P.M.; Palmer, A.M.; Wisniewski, S.R.; DeKosky, S.T. Treatment of traumatic brain injury with moderate hypothermia. N. Engl. J. Med., 1997, 336(8), 540-546.
[] [PMID: 9023090]
Jiang, J.Y.; Xu, W.; Li, W.P.; Gao, G.Y.; Bao, Y.H.; Liang, Y.M.; Luo, Q.Z. Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury. J. Cereb. Blood Flow Metab., 2006, 26(6), 771-776.
[] [PMID: 16306933]
Adelson, P.D.; Wisniewski, S.R.; Beca, J.; Brown, S.D.; Bell, M.; Muizelaar, J.P.; Okada, P.; Beers, S.R.; Balasubramani, G.K.; Hirtz, D. Paediatric Traumatic Brain Injury, C. Paediatric Traumatic Brain Injury Consortium. Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): a phase 3, randomised controlled trial. Lancet Neurol., 2013, 12(6), 546-553.
[] [PMID: 23664370]
Beca, J.; McSharry, B.; Erickson, S.; Yung, M.; Schibler, A.; Slater, A.; Wilkins, B.; Singhal, A.; Williams, G.; Sherring, C.; Butt, W. Pediatric Study Group of the Australia and New Zealand Intensive Care Society Clinical Trials Group. Pediatric Study Group of the A, New Zealand Intensive Care Society Clinical Trials G: Hypothermia for traumatic brain injury in children-a phase ii randomized controlled trial. Crit. Care Med., 2015, 43(7), 1458-1466.
[] [PMID: 25803648]
Lei, J.; Gao, G.; Mao, Q.; Feng, J.; Wang, L.; You, W.; Jiang, J. LTH-1 trial collaborators. Rationale, methodology, and implementation of a nationwide multicenter randomized controlled trial of long-term mild hypothermia for severe traumatic brain injury (the LTH-1 trial). Contemp. Clin. Trials, 2015, 40, 9-14.
[] [PMID: 25460339]
Nichol, A.; Gantner, D.; Presneill, J.; Murray, L.; Trapani, T.; Bernard, S.; Cameron, P.; Capellier, G.; Forbes, A.; McArthur, C.; Newby, L.; Rashford, S.; Rosenfeld, J.V.; Smith, T.; Stephenson, M.; Varma, D.; Walker, T.; Webb, S.; Cooper, D.J. Protocol for a multicentre randomised controlled trial of early and sustained prophylactic hypothermia in the management of traumatic brain injury. Crit. Care Resusc., 2015, 17(2), 92-100.
[PMID: 26017126]
Andrews, P.J.; Harris, B.A.; Murray, G.D. Hypothermia for intracranial hypertension after traumatic brain injury. N. Engl. J. Med., 2016, 374(14), 1385.
[PMID: 27050212]
Flynn, L.M.; Rhodes, J.; Andrews, P.J. Therapeutic hypothermia reduces intracranial pressure and partial brain oxygen tension in patients with severe traumatic brain injury: Preliminary data from the eurotherm3235 trial. Ther. Hypothermia Temp. Manag., 2015, 5(3), 143-151.
[] [PMID: 26060880]
Martirosyan, N.L.; Patel, A.A.; Carotenuto, A.; Kalani, M.Y.; Bohl, M.A.; Preul, M.C.; Theodore, N. The role of therapeutic hypothermia in the management of acute spinal cord injury. Clin. Neurol. Neurosurg., 2017, 154, 79-88.
[] [PMID: 28131967]
Ahmad, F.U.; Wang, M.Y.; Levi, A.D. Hypothermia for acute spinal cord injury--a review. World Neurosurg., 2014, 82(1-2), 207-214.
[] [PMID: 23298671]
Yamamoto, K.; Ishikawa, T.; Sakabe, T.; Taguchi, T.; Kawai, S.; Marsala, M. The hydroxyl radical scavenger Nicaraven inhibits glutamate release after spinal injury in rats. Neuroreport, 1998, 9(7), 1655-1659.
[] [PMID: 9631482]
Yu, W.R.; Westergren, H.; Farooque, M.; Holtz, A.; Olsson, Y. Systemic hypothermia following spinal cord compression injury in the rat: an immunohistochemical study on MAP 2 with special reference to dendrite changes. Acta Neuropathol., 2000, 100(5), 546-552.
[] [PMID: 11045677]
Yu, W.R.; Westergren, H.; Farooque, M.; Holtz, A.; Olsson, Y. Systemic hypothermia following compression injury of rat spinal cord: reduction of plasma protein extravasation demonstrated by immunohistochemistry. Acta Neuropathol., 1999, 98(1), 15-21.
[] [PMID: 10412796]
Chatzipanteli, K.; Yanagawa, Y.; Marcillo, A.E.; Kraydieh, S.; Yezierski, R.P.; Dietrich, W.D. Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. J. Neurotrauma, 2000, 17(4), 321-332.
[] [PMID: 10776915]
Westergren, H.; Farooque, M.; Olsson, Y.; Holtz, A. Spinal cord blood flow changes following systemic hypothermia and spinal cord compression injury: an experimental study in the rat using Laser-Doppler flowmetry. Spinal Cord, 2001, 39(2), 74-84.
[] [PMID: 11402362]
Zager, E.L.; Ames, A., III Reduction of cellular energy requirements. Screening for agents that may protect against CNS ischemia. J. Neurosurg., 1988, 69(4), 568-579.
[] [PMID: 3418390]
Ji, X.; Luo, Y.; Ling, F.; Stetler, R.A.; Lan, J.; Cao, G.; Chen, J. Mild hypothermia diminishes oxidative DNA damage and pro-death signaling events after cerebral ischemia: A mechanism for neuroprotection. Front. Biosci., 2007, 12, 1737-1747.
Ohmura, A.; Nakajima, W.; Ishida, A.; Yasuoka, N.; Kawamura, M.; Miura, S.; Takada, G. Prolonged hypothermia protects neonatal rat brain against hypoxic-ischemia by reducing both apoptosis and necrosis. Brain Dev., 2005, 27(7), 517-526.
[] [PMID: 15899566]
Hägerdal, M.; Harp, J.; Siesjö, B.K. Effect of hypothermia upon organic phosphates, glycolytic metabolites, citric acid cycle intermediates and associated amino acids in rat cerebral cortex. J. Neurochem., 1975, 24(4), 743-748.
[] [PMID: 1123628]
Ehrlich, M.P.; McCullough, J.N.; Zhang, N.; Weisz, D.J.; Juvonen, T.; Bodian, C.A.; Griepp, R.B. Effect of hypothermia on cerebral blood flow and metabolism in the pig. Ann. Thorac. Surg., 2002, 73(1), 191-197.
[] [PMID: 11834009]
Matsumoto, M.; Scheller, M.S.; Zornow, M.H.; Strnat, M.A. Effect of S-emopamil, nimodipine, and mild hypothermia on hippocampal glutamate concentrations after repeated cerebral ischemia in rabbits. Stroke, 1993, 24(8), 1228-1234.
[] [PMID: 8102022]
Busto, R.; Dietrich, W.D.; Globus, M.Y.; Valdés, I.; Scheinberg, P.; Ginsberg, M.D. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J. Cereb. Blood Flow Metab., 1987, 7(6), 729-738.
[] [PMID: 3693428]
Colbourne, F.; Grooms, S.Y.; Zukin, R.S.; Buchan, A.M.; Bennett, M.V. Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia. Proc. Natl. Acad. Sci. USA, 2003, 100(5), 2906-2910.
[] [PMID: 12606709]
Kim, J.Y.; Kim, N.; Yenari, M.A.; Chang, W. Mild hypothermia suppresses calcium-sensing receptor (casr) induction following forebrain ischemia while increasing gaba-b receptor 1 (gaba-b-r1) expression. Transl. Stroke Res., 2011, 2(2), 195-201.
[] [PMID: 21731589]
Ginsberg, M.D.; Sternau, L.L.; Globus, M.Y.; Dietrich, W.D.; Busto, R. Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc. Brain Metab. Rev., 1992, 4(3), 189-225.
[PMID: 1389956]
Kamme, F.; Campbell, K.; Wieloch, T. Biphasic expression of the fos and jun families of transcription factors following transient forebrain ischaemia in the rat. Effect of hypothermia. Eur. J. Neurosci., 1995, 7(10), 2007-2016.
[] [PMID: 8542058]
Yenari, M.A.; Liu, J.; Zheng, Z.; Vexler, Z.S.; Lee, J.E.; Giffard, R.G. Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection. Ann. N. Y. Acad. Sci., 2005, 1053, 74-83.
[] [PMID: 16179510]
Terao, Y.; Miyamoto, S.; Hirai, K.; Kamiguchi, H.; Ohta, H.; Shimojo, M.; Kiyota, Y.; Asahi, S.; Sakura, Y.; Shintani, Y. Hypothermia enhances heat-shock protein 70 production in ischemic brains. Neuroreport, 2009, 20(8), 745-749.
[] [PMID: 19352207]
Truettner, J.S.; Alonso, O.F.; Bramlett, H.M.; Dietrich, W.D. Therapeutic hypothermia alters microRNA responses to traumatic brain injury in rats. J. Cereb. Blood Flow Metab., 2011, 31(9), 1897-1907.
[] [PMID: 21505482]
Tang, X.N.; Yenari, M.A. Hypothermia as a cytoprotective strategy in ischemic tissue injury. Ageing Res. Rev., 2010, 9(1), 61-68.
[] [PMID: 19833233]
Holcik, M.; Lefebvre, C.; Yeh, C.; Chow, T.; Korneluk, R.G. A new internal-ribosome-entry-site motif potentiates XIAP-mediated cytoprotection. Nat. Cell Biol., 1999, 1(3), 190-192.
[] [PMID: 10559907]
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.
[] [PMID: 20546708]
Chip, S.; Zelmer, A.; Ogunshola, O.O.; Felderhoff-Mueser, U.; Nitsch, C.; Bührer, C.; Wellmann, S. The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection. Neurobiol. Dis., 2011, 43(2), 388-396.
[] [PMID: 21527344]
Green, D.R.; Reed, J.C. Mitochondria and apoptosis. Science, 1998, 281(5381), 1309-1312.
[] [PMID: 9721092]
Ashkenazi, A.; Dixit, V.M. Death receptors: signaling and modulation. Science, 1998, 281(5381), 1305-1308.
[] [PMID: 9721089]
Prakasa Babu, P.; Yoshida, Y.; Su, M.; Segura, M.; Kawamura, S.; Yasui, N. Immunohistochemical expression of Bcl-2, Bax and cytochrome c following focal cerebral ischemia and effect of hypothermia in rat. Neurosci. Lett., 2000, 291(3), 196-200.
[] [PMID: 10984640]
Slikker, W., III; Desai, V.G.; Duhart, H.; Feuers, R.; Imam, S.Z. Hypothermia enhances bcl-2 expression and protects against oxidative stress-induced cell death in Chinese hamster ovary cells. Free Radic. Biol. Med., 2001, 31(3), 405-411.
[] [PMID: 11461779]
Zhang, Z.; Sobel, R.A.; Cheng, D.; Steinberg, G.K.; Yenari, M.A. Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia. Brain Res. Mol. Brain Res., 2001, 95(1-2), 75-85.
[] [PMID: 11687278]
Inamasu, J.; Suga, S.; Sato, S.; Horiguchi, T.; Akaji, K.; Mayanagi, K.; Kawase, T. Postischemic hypothermia attenuates apoptotic cell death in transient focal ischemia in rats. Acta Neurochir. Suppl., 2000, 76, 525-527.
[] [PMID: 11450083]
Yenari, M.A.; Iwayama, S.; Cheng, D.; Sun, G.H.; Fujimura, M.; Morita-Fujimura, Y.; Chan, P.H.; Steinberg, G.K. Mild hypothermia attenuates cytochrome c release but does not alter Bcl-2 expression or caspase activation after experimental stroke. J. Cereb. Blood Flow Metab., 2002, 22(1), 29-38.
[] [PMID: 11807391]
Phanithi, P.B.; Yoshida, Y.; Santana, A.; Su, M.; Kawamura, S.; Yasui, N. Mild hypothermia mitigates post-ischemic neuronal death following focal cerebral ischemia in rat brain: immunohistochemical study of Fas, caspase-3 and TUNEL. Neuropathology, 2000, 20(4), 273-282.
[PMID: 11211051]
Xu, L.; Yenari, M.A.; Steinberg, G.K.; Giffard, R.G. Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J. Cereb. Blood Flow Metab., 2002, 22(1), 21-28.
[] [PMID: 11807390]
Bright, R.; Raval, A.P.; Dembner, J.M.; Pérez-Pinzón, M.A.; Steinberg, G.K.; Yenari, M.A.; Mochly-Rosen, D. Protein kinase C delta mediates cerebral reperfusion injury in vivo. J. Neurosci., 2004, 24(31), 6880-6888.
[] [PMID: 15295022]
Raval, A.P.; Dave, K.R.; Prado, R.; Katz, L.M.; Busto, R.; Sick, T.J.; Ginsberg, M.D.; Mochly-Rosen, D.; Pérez-Pinzón, M.A. Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation. J. Cereb. Blood Flow Metab., 2005, 25(6), 730-741.
[] [PMID: 15716854]
Lee, S.M.; Zhao, H.; Maier, C.M.; Steinberg, G.K. The protective effect of early hypothermia on PTEN phosphorylation correlates with free radical inhibition in rat stroke. J. Cereb. Blood Flow Metab., 2009, 29(9), 1589-1600.
[] [PMID: 19553907]
Shimohata, T.; Zhao, H.; Steinberg, G.K. Epsilon PKC may contribute to the protective effect of hypothermia in a rat focal cerebral ischemia model. Stroke, 2007, 38(2), 375-380.
[] [PMID: 17204679]
Hamann, G.F.; Burggraf, D.; Martens, H.K.; Liebetrau, M.; Jäger, G.; Wunderlich, N.; DeGeorgia, M.; Krieger, D.W. Mild to moderate hypothermia prevents microvascular basal lamina antigen loss in experimental focal cerebral ischemia. Stroke, 2004, 35(3), 764-769.
[] [PMID: 14976330]
Lee, J.E.; Yoon, Y.J.; Moseley, M.E.; Yenari, M.A. 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(2), 289-297.
[] [PMID: 16175859]
Liu, L.; Kim, J.Y.; Koike, M.A.; Yoon, Y.J.; Tang, X.N.; Ma, H.; Lee, H.; Steinberg, G.K.; Lee, J.E.; Yenari, M.A. FasL shedding is reduced by hypothermia in experimental stroke. J. Neurochem., 2008, 106(2), 541-550.
[] [PMID: 18410517]
Kim, J.Y.; Kim, N.; Lee, J.E.; Yenari, M.A. Hypothermia identifies dynamin as a potential therapeutic target in experimental stroke. Ther. Hypothermia Temp. Manag., 2017, 7(3), 171-177.
[] [PMID: 28665255]
Susin, S.A.; Lorenzo, H.K.; Zamzami, N.; Marzo, I.; Snow, B.E.; Brothers, G.M.; Mangion, J.; Jacotot, E.; Costantini, P.; Loeffler, M.; Larochette, N.; Goodlett, D.R.; Aebersold, R.; Siderovski, D.P.; Penninger, J.M.; Kroemer, G. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature, 1999, 397(6718), 441-446.
[] [PMID: 9989411]
Zhao, H.; Wang, J.Q.; Shimohata, T.; Sun, G.; Yenari, M.A.; Sapolsky, R.M.; Steinberg, G.K. 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.
[] [PMID: 17886565]
Shi, G.D.; OuYang, Y.P.; Shi, J.G.; Liu, Y.; Yuan, W.; Jia, L.S. PTEN deletion prevents ischemic brain injury by activating the mTOR signaling pathway. Biochem. Biophys. Res. Commun., 2011, 404(4), 941-945.
[] [PMID: 21185267]
Zhao, H.; Steinberg, G.K.; Sapolsky, R.M. General versus specific actions of mild-moderate hypothermia in attenuating cerebral ischemic damage. J. Cereb. Blood Flow Metab., 2007, 27(12), 1879-1894.
[] [PMID: 17684517]
Vosler, P.S.; Logue, E.S.; Repine, M.J.; Callaway, C.W. Delayed hypothermia preferentially increases expression of brain-derived neurotrophic factor exon III in rat hippocampus after asphyxial cardiac arrest. Brain Res. Mol. Brain Res., 2005, 135(1-2), 21-29.
[] [PMID: 15857665]
D’Cruz, B.J.; Fertig, K.C.; Filiano, A.J.; Hicks, S.D.; DeFranco, D.B.; Callaway, C.W. Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. J. Cereb. Blood Flow Metab., 2002, 22(7), 843-851.
[] [PMID: 12142569]
Schmidt, K.M.; Repine, M.J.; Hicks, S.D.; DeFranco, D.B.; Callaway, C.W. Regional changes in glial cell line-derived neurotrophic factor after cardiac arrest and hypothermia in rats. Neurosci. Lett., 2004, 368(2), 135-139.
[] [PMID: 15351435]
Boris-Möller, F.; Kamme, F.; Wieloch, T. The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat. Brain Res. Mol. Brain Res., 1998, 63(1), 163-173.
[] [PMID: 9838092]
Schmitt, K.R.; Diestel, A.; Lehnardt, S.; Schwartlander, R.; Lange, P.E.; Berger, F.; Ullrich, O.; Abdul-Khaliq, H. Hypothermia suppresses inflammation via ERK signaling pathway in stimulated microglial cells. J. Neuroimmunol., 2007, 189(1-2), 7-16.
[] [PMID: 17651818]
Zhao, H.; Shimohata, T.; Wang, J.Q.; Sun, G.; Schaal, D.W.; Sapolsky, R.M.; Steinberg, G.K. Akt contributes to neuroprotection by hypothermia against cerebral ischemia in rats. J. Neurosci., 2005, 25(42), 9794-9806.
[] [PMID: 16237183]
Mehta, S.L.; Manhas, N.; Raghubir, R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res. Brain Res. Rev., 2007, 54(1), 34-66.
[] [PMID: 17222914]
Kim, J.Y.; Kawabori, M.; Yenari, M.A. Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets. Curr. Med. Chem., 2014, 21(18), 2076-2097.
[] [PMID: 24372209]
Wang, Q.; Tang, X.N.; Yenari, M.A. The inflammatory response in stroke. J. Neuroimmunol., 2007, 184(1-2), 53-68.
[] [PMID: 17188755]
Ceulemans, A.G.; Zgavc, T.; Kooijman, R.; Hachimi-Idrissi, S.; Sarre, S.; Michotte, Y. The dual role of the neuroinflammatory response after ischemic stroke: modulatory effects of hypothermia. J. Neuroinflammation, 2010, 7, 74.
[] [PMID: 21040547]
Rivest, S. Regulation of innate immune responses in the brain. Nat. Rev. Immunol., 2009, 9(6), 429-439.
[] [PMID: 19461673]
Zheng, Z.; Yenari, M.A. Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol. Res., 2004, 26(8), 884-892.
[] [PMID: 15727272]
Ransohoff, R.M. Immunology: Barrier to electrical storms. Nature, 2009, 457(7226), 155-156.
[] [PMID: 19129836]
Van Hemelrijck, A.; Vermijlen, D.; Hachimi-Idrissi, S.; Sarre, S.; Ebinger, G.; Michotte, Y. Effect of resuscitative mild hypothermia on glutamate and dopamine release, apoptosis and ischaemic brain damage in the endothelin-1 rat model for focal cerebral ischaemia. J. Neurochem., 2003, 87(1), 66-75.
[] [PMID: 12969253]
Patel, A.R.; Ritzel, R.; McCullough, L.D.; Liu, F. Microglia and ischemic stroke: a double-edged sword. Int. J. Physiol. Pathophysiol. Pharmacol., 2013, 5(2), 73-90.
[PMID: 23750306]
Ghosh, S.; May, M.J.; Kopp, E.B. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol., 1998, 16, 225-260.
[] [PMID: 9597130]
Yilmaz, G.; Granger, D.N. Cell adhesion molecules and ischemic stroke. Neurol. Res., 2008, 30(8), 783-793.
[] [PMID: 18826804]
Yenari, M.A.; Han, H.S. Influence of hypothermia on post-ischemic inflammation: role of nuclear factor kappa B (NFkappaB). Neurochem. Int., 2006, 49(2), 164-169.
[] [PMID: 16750872]
Choi, J.S.; Park, J.; Suk, K.; Moon, C.; Park, Y.K.; Han, H.S. Mild hypothermia attenuates intercellular adhesion molecule-1 induction via activation of extracellular signal-regulated kinase-1/2 in a focal cerebral ischemia model. Stroke Res. Treat., 2011, 2011846716
[] [PMID: 21716663]
Tong, G.; Krauss, A.; Mochner, J.; Wollersheim, S.; Soltani, P.; Berger, F.; Schmitt, K.R.L. Deep hypothermia therapy attenuates LPS-induced microglia neuroinflammation via the STAT3 pathway. Neuroscience, 2017, 358, 201-210.
[] [PMID: 28687308]
Trendelenburg, G. Acute neurodegeneration and the inflammasome: central processor for danger signals and the inflammatory response? J. Cereb. Blood Flow Metab., 2008, 28(5), 867-881.
[] [PMID: 18212795]
Matsui, T.; Kakeda, T. IL-10 production is reduced by hypothermia but augmented by hyperthermia in rat microglia. J. Neurotrauma, 2008, 25(6), 709-715.
[] [PMID: 18533891]
Sugawara, T.; Chan, P.H. Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid. Redox Signal., 2003, 5(5), 597-607.
[] [PMID: 14580316]
Wong, C.H.; Crack, P.J. Modulation of neuro-inflammation and vascular response by oxidative stress following cerebral ischemia-reperfusion injury. Curr. Med. Chem., 2008, 15(1), 1-14.
[] [PMID: 18220759]
Globus, M.Y.; Busto, R.; Lin, B.; Schnippering, H.; Ginsberg, M.D. Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. J. Neurochem., 1995, 65(3), 1250-1256.
[] [PMID: 7643104]
Maier, C.M.; Sun, G.H.; Cheng, D.; Yenari, M.A.; Chan, P.H.; Steinberg, G.K. Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia. Neurobiol. Dis., 2002, 11(1), 28-42.
[] [PMID: 12460544]
Liu, L.; Yenari, M.A. Therapeutic hypothermia: neuroprotective mechanisms. Front. Biosci., 2006, 12, 816-825.
[] [PMID: 17127332]
Moro, M.A.; Cárdenas, A.; Hurtado, O.; Leza, J.C.; Lizasoain, I. Role of nitric oxide after brain ischaemia. Cell Calcium, 2004, 36(3-4), 265-275.
[] [PMID: 15261482]
Deng, H.; Han, H.S.; Cheng, D.; Sun, G.H.; Yenari, M.A. Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation. Stroke, 2003, 34(10), 2495-2501.
[] [PMID: 12970518]
Dietrich, W.D.; 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(5), 486-497.
[] [PMID: 2273405]
Kawanishi, M.; Kawai, N.; Nakamura, T.; Luo, C.; Tamiya, T.; Nagao, S. Effect of delayed mild brain hypothermia on edema formation after intracerebral hemorrhage in rats. J. Stroke Cerebrovasc. Dis., 2008, 17(4), 187-195.
[] [PMID: 18589338]
Baumann, E.; Preston, E.; Slinn, J.; Stanimirovic, D. Post-ischemic hypothermia attenuates loss of the vascular basement membrane proteins, agrin and SPARC, and the blood-brain barrier disruption after global cerebral ischemia. Brain Res., 2009, 1269, 185-197.
[] [PMID: 19285050]
Montaner, J.; Alvarez-Sabín, J.; Molina, C.; Anglés, A.; Abilleira, S.; Arenillas, J.; González, M.A.; Monasterio, J. Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke, 2001, 32(8), 1759-1766.
[] [PMID: 11486102]
Gidday, J.M.; Gasche, Y.G.; Copin, J.C.; Shah, A.R.; Perez, R.S.; Shapiro, S.D.; Chan, P.H.; Park, T.S. Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am. J. Physiol. Heart Circ. Physiol., 2005, 289(2), H558-H568.
[] [PMID: 15764676]
Kurisu, K.; Abumiya, T.; Nakamura, H.; Shimbo, D.; Shichinohe, H.; Nakayama, N.; Kazumata, K.; Shimizu, H.; Houkin, K. Transarterial regional brain hypothermia inhibits acute aquaporin-4 surge and sequential microvascular events in ischemia/reperfusion injury. Neurosurgery, 2016, 79(1), 125-134.
[] [PMID: 26516820]
Manley, G.T.; Fujimura, M.; Ma, T.; Noshita, N.; Filiz, F.; Bollen, A.W.; Chan, P.; Verkman, A.S. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat. Med., 2000, 6(2), 159-163.
[] [PMID: 10655103]
Xiao, F.; Arnold, T.C.; Zhang, S.; Brown, C.; Alexander, J.S.; Carden, D.L.; Conrad, S.A. Cerebral cortical aquaporin-4 expression in brain edema following cardiac arrest in rats. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2004, 11, 1001-1007.
Kernie, S.G.; Parent, J.M. Forebrain neurogenesis after focal Ischemic and traumatic brain injury. Neurobiol. Dis., 2010, 37(2), 267-274.
[] [PMID: 19909815]
Font, M.A.; Arboix, A.; Krupinski, J. Angiogenesis, neurogenesis and neuroplasticity in ischemic stroke. Curr. Cardiol. Rev., 2010, 6(3), 238-244.
[] [PMID: 21804783]
Shruster, A.; Melamed, E.; Offen, D. Neurogenesis in the aged and neurodegenerative brain. Apoptosis, 2010, 15(11), 1415-1421.
[] [PMID: 20339917]
Saito, K.; Fukuda, N.; Matsumoto, T.; Iribe, Y.; Tsunemi, A.; Kazama, T.; Yoshida-Noro, C.; Hayashi, N. Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein. Brain Res., 2010, 1358, 20-29.
[] [PMID: 20735994]
Kanagawa, T.; Fukuda, H.; Tsubouchi, H.; Komoto, Y.; Hayashi, S.; Fukui, O.; Shimoya, K.; Murata, Y. A decrease of cell proliferation by hypothermia in the hippocampus of the neonatal rat. Brain Res., 2006, 1111(1), 36-40.
[] [PMID: 16904084]
Xiong, M.; Cheng, G.Q.; Ma, S.M.; Yang, Y.; Shao, X.M.; Zhou, W.H. Post-ischemic hypothermia promotes generation of neural cells and reduces apoptosis by Bcl-2 in the striatum of neonatal rat brain. Neurochem. Int., 2011, 58(6), 625-633.
[] [PMID: 21300124]
Silasi, G.; Colbourne, F. Therapeutic hypothermia influences cell genesis and survival in the rat hippocampus following global ischemia. J. Cereb. Blood Flow Metab., 2011, 31(8), 1725-1735.
[] [PMID: 21364603]
Lasarzik, I.; Winkelheide, U.; Thal, S.C.; Benz, N.; Lörscher, M.; Jahn-Eimermacher, A.; Werner, C.; Engelhard, K. Mild hypothermia has no long-term impact on postischemic neurogenesis in rats. Anesth. Analg., 2009, 109(5), 1632-1639.
[] [PMID: 19843801]
Bennet, L.; Roelfsema, V.; George, S.; Dean, J.M.; Emerald, B.S.; Gunn, A.J. The effect of cerebral hypothermia on white and grey matter injury induced by severe hypoxia in preterm fetal sheep. J. Physiol., 2007, 578(Pt 2), 491-506.
[] [PMID: 17095565]
Matijasevic, Z.; Snyder, J.E.; Ludlum, D.B. Hypothermia causes a reversible, p53-mediated cell cycle arrest in cultured fibroblasts. Oncol. Res., 1998, 10(11-12), 605-610.
[PMID: 10367942]
Gopurappilly, R.; Pal, R.; Mamidi, M.K.; Dey, S.; Bhonde, R.; Das, A.K. Stem cells in stroke repair: current success and future prospects. CNS Neurol. Disord. Drug Targets, 2011, 10(6), 741-756.
[] [PMID: 21838668]
Li, L.; Harms, K.M.; Ventura, P.B.; Lagace, D.C.; Eisch, A.J.; Cunningham, L.A. Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic. Glia, 2010, 58(13), 1610-1619.
[] [PMID: 20578055]
Hawthorne, A.L.; Hu, H.; Kundu, B.; Steinmetz, M.P.; Wylie, C.J.; Deneris, E.S.; Silver, J. The unusual response of serotonergic neurons after CNS Injury: lack of axonal dieback and enhanced sprouting within the inhibitory environment of the glial scar. J. Neurosci., 2011, 31(15), 5605-5616.
[] [PMID: 21490201]
Trendelenburg, G.; Dirnagl, U. Neuroprotective role of astrocytes in cerebral ischemia: focus on ischemic preconditioning. Glia, 2005, 50(4), 307-320.
[] [PMID: 15846804]
Xie, Y.C.; Li, C.Y.; Li, T.; Nie, D.Y.; Ye, F. Effect of mild hypothermia on angiogenesis in rats with focal cerebral ischemia. Neurosci. Lett., 2007, 422(2), 87-90.
[] [PMID: 17630209]
Kao, C.H.; Chio, C.C.; Lin, M.T.; Yeh, C.H. Body cooling ameliorating spinal cord injury may be neurogenesis-, anti-inflammation- and angiogenesis-associated in rats. J. Trauma, 2011, 70(4), 885-893.
[] [PMID: 20693909]
Kuo, J.R.; Lo, C.J.; Chang, C.P.; Lin, H.J.; Lin, M.T.; Chio, C.C. Brain cooling-stimulated angiogenesis and neurogenesis attenuated traumatic brain injury in rats. J. Trauma, 2010, 69(6), 1467-1472.
[] [PMID: 21150525]
Lotocki, G.; de Rivero Vaccari, J.; Alonso, O.; Molano, J.S.; Nixon, R.; Dietrich, W.D.; Bramlett, H.M. Oligodendrocyte vulnerability following traumatic brain injury in rats: Effect of moderate hypothermia. Ther. Hypothermia Temp. Manag., 2011, 1(1), 43-51.
[] [PMID: 23336085]
Imada, S.; Yamamoto, M.; Tanaka, K.; Seiwa, C.; Watanabe, K.; Kamei, Y.; Kozuma, S.; Taketani, Y.; Asou, H. Hypothermia-induced increase of oligodendrocyte precursor cells: Possible involvement of plasmalemmal voltage-dependent anion channel 1. J. Neurosci. Res., 2010, 88(16), 3457-3466.
[] [PMID: 20936704]
Schmitt, K.R.; Boato, F.; Diestel, A.; Hechler, D.; Kruglov, A.; Berger, F.; Hendrix, S. Hypothermia-induced neurite outgrowth is mediated by tumor necrosis factor-alpha. Brain Pathol., 2010, 20(4), 771-779.
[] [PMID: 20070303]
Wang, X.; Zhu, S.; Drozda, M.; Zhang, W.; Stavrovskaya, I.G.; Cattaneo, E.; Ferrante, R.J.; Kristal, B.S.; Friedlander, R.M. Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington’s disease. Proc. Natl. Acad. Sci. USA, 2003, 100(18), 10483-10487.
[] [PMID: 12930891]
Tikka, T.M.; Koistinaho, J.E. Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia. J. Immunol., 2001, 166(12), 7527-7533.
[] [PMID: 11390507]
Tikka, T.; Fiebich, B.L.; Goldsteins, G.; Keinanen, R.; Koistinaho, J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J. Neurosci., 2001, 21(8), 2580-2588.
[] [PMID: 11306611]
Yrjänheikki, J.; Tikka, T.; Keinänen, R.; Goldsteins, G.; Chan, P.H.; Koistinaho, J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc. Natl. Acad. Sci. USA, 1999, 96(23), 13496-13500.
[] [PMID: 10557349]
Murata, Y.; Rosell, A.; Scannevin, R.H.; Rhodes, K.J.; Wang, X.; Lo, E.H. Extension of the thrombolytic time window with minocycline in experimental stroke. Stroke, 2008, 39(12), 3372-3377.
[] [PMID: 18927459]
Lampl, Y.; Boaz, M.; Gilad, R.; Lorberboym, M.; Dabby, R.; Rapoport, A.; Anca-Hershkowitz, M.; Sadeh, M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology, 2007, 69(14), 1404-1410.
[] [PMID: 17909152]
Fagan, S.C.; Waller, J.L.; Nichols, F.T.; Edwards, D.J.; Pettigrew, L.C.; Clark, W.M.; Hall, C.E.; Switzer, J.A.; Ergul, A.; Hess, D.C. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke, 2010, 41(10), 2283-2287.
[] [PMID: 20705929]
Switzer, J.A.; Hess, D.C.; Ergul, A.; Waller, J.L.; Machado, L.S.; Portik-Dobos, V.; Pettigrew, L.C.; Clark, W.M.; Fagan, S.C. Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke. Stroke, 2011, 42(9), 2633-2635.
[] [PMID: 21737808]
Blacker, D.J.; Prentice, D.; Alvaro, A.; Bates, T.R.
Bynevelt, M.; Kelly, A.; Kho, L.K.; Kohler, E.; Hankey, G.J.; Thompson, A.; Major, T. Reducing haemorrhagic transformation after thrombolysis for stroke: a strategy utilising minocycline. Stroke Res. Treat., 2013, 2013362961
[] [PMID: 23691430]
Chang, J.J.; Kim-Tenser, M.; Emanuel, B.A.; Jones, G.M.; Chapple, K.; Alikhani, A.; Sanossian, N.; Mack, W.J.; Tsivgoulis, G.; Alexandrov, A.V.; Pourmotabbed, T. Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study. Eur. J. Neurol., 2017, 24(11), 1384-1391.
[] [PMID: 28929560]
Kappos, L.; Radue, E.W.; O’Connor, P.; Polman, C.; Hohlfeld, R.; Calabresi, P.; Selmaj, K.; Agoropoulou, C.; Leyk, M.; Zhang-Auberson, L.; Burtin, P.; Group, F.S. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med., 2010, 362(5), 387-401.
[] [PMID: 20089952]
Brait, V.H.; Tarrasón, G.; Gavaldà, A.; Godessart, N.; Planas, A.M. Selective sphingosine 1-phosphate receptor 1 agonist is protective against ischemia/reperfusion in mice. Stroke, 2016, 47(12), 3053-3056.
[] [PMID: 27827329]
Liu, J.; Zhang, C.; Tao, W.; Liu, M. Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke. Int. J. Neurosci., 2013, 123(3), 163-169.
[] [PMID: 23167788]
Gao, C.; Qian, Y.; Huang, J.; Wang, D.; Su, W.; Wang, P.; Guo, L.; Quan, W.; An, S.; Zhang, J.; Jiang, R. A three-day consecutive fingolimod administration improves neurological functions and modulates multiple immune responses of cci mice. Mol. Neurobiol., 2017, 54(10), 8348-8360.
[] [PMID: 27924525]
Zhang, L.; Ding, K.; Wang, H.; Wu, Y.; Xu, J. Traumatic brain injury-induced neuronal apoptosis is reduced through modulation of pi3k and autophagy pathways in mouse by fty720. Cell. Mol. Neurobiol., 2016, 36(1), 131-142.
[] [PMID: 26099903]
Campos, F.; Qin, T.; Castillo, J.; Seo, J.H.; Arai, K.; Lo, E.H.; Waeber, C. Fingolimod reduces hemorrhagic transformation associated with delayed tissue plasminogen activator treatment in a mouse thromboembolic model. Stroke, 2013, 44(2), 505-511.
[] [PMID: 23287783]
Massberg, S.; von Andrian, U.H. Fingolimod and sphingosine-1-phosphate--modifiers of lymphocyte migration. N. Engl. J. Med., 2006, 355(11), 1088-1091.
[] [PMID: 16971715]
Hasegawa, Y.; Suzuki, H.; Sozen, T.; Rolland, W.; Zhang, J.H. Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke, 2010, 41(2), 368-374.
[] [PMID: 19940275]
Fu, Y.; Zhang, N.; Ren, L.; Yan, Y.; Sun, N.; Li, Y.J.; Han, W.; Xue, R.; Liu, Q.; Hao, J.; Yu, C.; Shi, F.D. Impact of an immune modulator fingolimod on acute ischemic stroke. Proc. Natl. Acad. Sci. USA, 2014, 111(51), 18315-18320.
[] [PMID: 25489101]
Zhu, Z.; Fu, Y.; Tian, D.; Sun, N.; Han, W.; Chang, G.; Dong, Y.; Xu, X.; Liu, Q.; Huang, D.; Shi, F.D. Combination of the immune modulator fingolimod with alteplase in acute ischemic stroke: A pilot trial. Circulation, 2015, 132(12), 1104-1112.
[] [PMID: 26202811]
Kobayashi, M.S.; Asai, S.; Ishikawa, K.; Nishida, Y.; Nagata, T.; Takahashi, Y. Global profiling of influence of intra-ischemic brain temperature on gene expression in rat brain. Brain Res. Brain Res. Rev., 2008, 58(1), 171-191.
[] [PMID: 18440647]
Kelly, S.; Yenari, M.A. Neuroprotection: heat shock proteins. Curr. Med. Res. Opin., 2002, 18(Suppl. 2), s55-s60.
[] [PMID: 12365831]
Kim, J.Y.; Kim, N.; Zheng, Z.; Lee, J.E.; Yenari, M.A. 70-kda heat shock protein downregulates dynamin in experimental stroke: A new therapeutic target? Stroke, 2016, 47(8), 2103-2111.
[] [PMID: 27387989]
Kim, J.Y.; Kim, N.; Zheng, Z.; Lee, J.E.; Yenari, M.A. The 70 kDa heat shock protein protects against experimental traumatic brain injury. Neurobiol. Dis., 2013, 58, 289-295.
[] [PMID: 23816752]
Kumar, K.; Wu, X.; Evans, A.T.; Marcoux, F. The effect of hypothermia on induction of heat shock protein (HSP)-72 in ischemic brain. Metab. Brain Dis., 1995, 10(4), 283-291.
[] [PMID: 8847992]
Lee, B.S.; Jung, E.; Lee, Y.; Chung, S.H. Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy. Cell Stress Chaperones, 2017, 22(3), 409-415.
[] [PMID: 28285429]

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