Remote ischaemic conditioning-a new paradigm of self-protection in the brain

Nature Reviews Neurology

Volumn 11, Issue 12, 2015, Pages 698-710

  Hess, David C ^a   Blauenfeldt, Rolf A ^c   Andersen, Grethe ^c   Hougaard, Kristina D ^c   Hoda, Md Nasrul ^b   Ding, Yuchuan ^d   Ji, Xunming ^e  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

^b AUGUSTA UNIVERSITY   (United States)

^c AARHUS UNIVERSITY HOSPITAL   (Denmark)

^d WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e CAPITAL MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

HUMORAL ANTIBODY; LIPOPOLYSACCHARIDE;

BLOOD PRESSURE; BRAIN BLOOD FLOW; BRAIN ISCHEMIA; CARDIOVASCULAR SURGERY; COGNITIVE DEFECT; COMORBIDITY; HEART INFARCTION; HEART PROTECTION; HUMAN; ISCHEMIC PRECONDITIONING; MIDDLE CEREBRAL ARTERY OCCLUSION; NERVOUS SYSTEM; NEUROLOGIC DISEASE; NEUROPROTECTION; PERCUTANEOUS CORONARY INTERVENTION; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; PRIORITY JOURNAL; REMOTE ISCHEMIC CONDITIONING; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION; SUBARACHNOID HEMORRHAGE; TRAUMATIC BRAIN INJURY; BRAIN; NERVOUS SYSTEM DISEASES; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; VASCULARIZATION;

BRAIN; BRAIN ISCHEMIA; HUMANS; NERVOUS SYSTEM DISEASES; NEUROPROTECTION; SIGNAL TRANSDUCTION;

EID: 84949313895     PISSN: 17594758     EISSN: 17594766     Source Type: Journal    
DOI: 10.1038/nrneurol.2015.223     Document Type: Review

References (168)

1. Iadecola, C., Anrather, J. Stroke research at a crossroad: asking the brain for directions. Nat. Neurosci. 14, 1363-1368 (2011).
2. Albers, G. W. et al. Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies. Stroke 42, 2645-2650 (2011).
3. Murry, C. E., Jennings, R. B., Reimer, K. A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124-1136 (1986).
4. Kharbanda, R. K. et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106, 2881-2883 (2002).
5. Bøtker, H. E. et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375, 727-734 (2010).
6. Vander Heide, R. Clinically useful cardioprotection: ischemic preconditioning then and now. J. Cardiovasc. Pharmacol. Ther. 16, 251-254 (2011).
7. Sloth, A. D. et al. Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. Eur. Heart J. 35, 168-175 (2014).
8. Pei, H. et al. Remote ischemic preconditioning reduces perioperative cardiac and renal events in patients undergoing elective coronary intervention: a meta-analysis of 11 randomized trials. PLoS ONE 9, e115500 (2014).
9. Brevoord, D. et al. Remote ischemic conditioning to protect against ischemia-reperfusion injury: a systematic review and meta-analysis. PLoS ONE 7, e42179 (2012).
10. Davies, W. R. et al. Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention: the CRISP stent trial long-term follow-up. Circ. Cardiovasc. Interv. 6, 246-251 (2013).
11. Hoole, S. P. et al. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation 119, 820-827 (2009).
12. Er, F. et al. Ischemic preconditioning for prevention of contrast medium-induced nephropathy: randomized pilot RenPro Trial (Renal Protection Trial). Circulation 126, 296-303 (2012).
13. Zarbock, A. et al. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA 313, 2133-2141 (2015).
14. Arumugam, T. V., Gleichmann, M., Tang, S. C., Mattson, M. P. Hormesis/preconditioning mechanisms, the nervous system and aging. Ageing Res. Rev. 5, 165-178 (2006).
15. Calabrese, E. J. Converging concepts: adaptive response, preconditioning, and the Yerkes-Dodson Law are manifestations of hormesis. Ageing Res. Rev. 7, 8-20 (2008).
16. Mattson, M. P. Hormesis defined. Ageing Res. Rev. 7, 1-7 (2008).
17. Dawson, D. A., Furuya, K., Gotoh, J., Nakao, Y., Hallenbeck, J. M. Cerebrovascular hemodynamics and ischemic tolerance: lipopolysaccharide-induced resistance to focal cerebral ischemia is not due to changes in severity of the initial ischemic insult, but is associated with preservation of microvascular perfusion. J. Cereb. Blood Flow Metab. 19, 616-623 (1999).
18. Bolli, R. The late phase of preconditioning. Circ. Res. 87, 972-983 (2000).
19. Guo, Y. et al. Demonstration of an early and a late phase of ischemic preconditioning in mice. Am. J. Physiol. 275, H1375-H1387 (1998).
20. Hausenloy, D. J., Yellon, D. M. The second window of preconditioning (SWOP) where are we now Cardiovasc. Drugs Ther. 24, 235-254 (2010).
21. Loukogeorgakis, S. P. et al. Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans: role of the autonomic nervous system. J. Am. Coll. Cardiol. 46, 450-456 (2005).
22. Wei, M. et al. Repeated remote ischemic postconditioning protects against adverse left ventricular remodeling and improves survival in a rat model of myocardial infarction. Circ. Res. 108, 1220-1225 (2011).
23. Rohailla, S. et al. Acute, delayed and chronic remote ischemic conditioning is associated with downregulation of mTOR and enhanced autophagy signaling. PLoS ONE 9, e111291 (2014).
24. Whittaker, P., Przyklenk, K. Reduction of infarct size in vivo with ischemic preconditioning: mathematical evidence for protection via non-ischemic tissue. Basic Res. Cardiol. 89, 6-15 (1994).
25. Przyklenk, K., Bauer, B., Ovize, M., Kloner, R. A., Whittaker, P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87, 893-899 (1993).
26. Gho, B. C., Schoemaker, R. G., van den Doel, M. A., Duncker, D. J., Verdouw, P. D. Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94, 2193-2200 (1996).
27. Birnbaum, Y., Hale, S. L., Kloner, R. A. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation 96, 1641-1646 (1997).
28. Schmidt, M. R. et al. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am. J. Physiol. Heart Circ. Physiol. 292, H1883-H1890 (2007).
29. Gross, G. J., Baker, J. E., Moore, J., Falck, J. R., Nithipatikom, K. Abdominal surgical incision induces remote preconditioning of trauma (RPCT) via activation of bradykinin receptors (BK2R) and the cytochrome P450 epoxygenase pathway in canine hearts. Cardiovasc. Drugs Ther. 25, 517-522 (2011).
30. Gross, G. J., Hsu, A., Gross, E. R., Falck, J. R., Nithipatikom, K. Factors mediating remote preconditioning of trauma in the rat heart: central role of the cytochrome p450 epoxygenase pathway in mediating infarct size reduction. J. Cardiovasc. Pharmacol. Ther. 18, 38-45 (2013).
31. Jones, W. K. et al. Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling. Circulation 120 (11 Suppl.), S1-S9 (2009).
32. Ren, X., Wang, Y., Jones, W. K. TNF-is required for late ischemic preconditioning but not for remote preconditioning of trauma. J. Surg. Res. 121, 120-129 (2004).
33. Redington, K. L. et al. Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors. Basic Res. Cardiol. 107, 241 (2012).
34. Dahl, N. A., Balfour, W. M. Prolonged anoxic survival due to anoxia pre-exposure: brain ATP, lactate, and pyruvate. Am. J. Physiol. 207, 452-456 (1964).
35. Lu, G. W., Yu, S., Li, R. H., Cui, X. Y., Gao, C. Y. Hypoxic preconditioning: a novel intrinsic cytoprotective strategy. Mol. Neurobiol. 31, 255-271 (2005).
36. Kitagawa, K. et al. 'Ischemic tolerance' phenomenon found in the brain. Brain Res. 528, 21-24 (1990).
37. Chen, J., Graham, S. H., Zhu, R. L., Simon, R. P. Stress proteins and tolerance to focal cerebral ischemia. J. Cereb. Blood Flow Metab. 16, 566-577 (1996).
38. Ottani, F. et al. Prodromal angina limits infarct size. A role for ischemic preconditioning. Circulation 91, 291-297 (1995).
39. Kloner, R. A. et al. Prospective temporal analysis of the onset of preinfarction angina versus outcome: an ancillary study in TIMI-9B. Circulation 97, 1042-1045 (1998).
40. Herrett, E. et al. Association between clinical presentations before myocardial infarction and coronary mortality: a prospective population-based study using linked electronic records. Eur. Heart J. 35, 2363-2371 (2014).
41. Moncayo, J., de Freitas, G. R., Bogousslavsky, J., Altieri, M., van Melle, G. Do transient ischemic attacks have a neuroprotective effect Neurology 54, 2089-2094 (2000).
42. Weih, M. et al. Attenuated stroke severity after prodromal TIA: a role for ischemic tolerance in the brain Stroke 30, 1851-1854 (1999).
43. Sitzer, M. et al. Transient ischaemic attack preceding anterior circulation infarction is independently associated with favourable outcome. J. Neurol. Neurosurg. Psychiatry 75, 659-660 (2004).
44. Wegener, S. et al. Transient ischemic attacks before ischemic stroke: preconditioning the human brain A multicenter magnetic resonance imaging study. Stroke 35, 616-621 (2004).
45. Weber, R., Diener, H. C., Weimar, C., German Stroke Study Collaboration. Why do acute ischemic stroke patients with a preceding transient ischemic attack present with less severe strokes Insights from the German Stroke Study. Eur. Neurol. 66, 265-270 (2011).
46. Johnston, S. C. Ischemic preconditioning from transient ischemic attacks Data from the Northern California TIA Study. Stroke 35 (11 Suppl. 1), 2680-2682 (2004).
47. Connolly, M. et al. Peripheral vascular disease as remote ischemic preconditioning, for acute stroke. Clin. Neurol. Neurosurg. 115, 2124-2129 (2013).
48. Malhotra, S., Naggar, I., Stewart, M., Rosenbaum, D. M. Neurogenic pathway mediated remote preconditioning protects the brain from transient focal ischemic injury. Brain Res. 1386, 184-190 (2011).
49. Wei, D., Ren, C., Chen, X., Zhao, H. The chronic protective effects of limb remote preconditioning and the underlying mechanisms involved in inflammatory factors in rat stroke. PLoS ONE 7, e30892 (2012).
50. Donato, M. et al. Role of the parasympathetic nervous system in cardioprotection by remote hindlimb ischaemic preconditioning. Exp. Physiol. 98, 425-434 (2013).
51. Steensrud, T. et al. Pretreatment with the nitric oxide donor SNAP or nerve transection blocks humoral preconditioning by remote limb ischemia or intra-arterial adenosine. Am. J. Physiol. Heart Circ. Physiol. 299, H1598-H1603 (2010).
52. Mastitskaya, S. et al. Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones. Cardiovasc. Res. 95, 487-494 (2012).
53. Shimizu, M. et al. Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence suggesting cross-species protection. Clin. Sci. (Lond.) 117, 191-200 (2009).
54. Konstantinov, I. E. et al. Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism. Transplantation 79, 1691-1695 (2005).
55. Jensen, R. V., Støttrup, N. B., Kristiansen, S. B., Bøtker, H. E. Release of a humoral circulating cardioprotective factor by remote ischemic preconditioning is dependent on preserved neural pathways in diabetic patients. Basic Res. Cardiol. 107, 285 (2012).
56. Hausenloy, D. J. et al. Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations. Basic Res. Cardiol. 105, 677-686 (2010).
57. Nakamura, M., Nakakimura, K., Matsumoto, M., Sakabe, T. Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A1 receptor antagonist. J. Cereb. Blood Flow Metab. 22, 161-170 (2002).
58. Xiao, L., Lu, R., Hu, C. P., Deng, H. W., Li, Y. J. Delayed cardioprotection by intestinal preconditioning is mediated by calcitonin gene-related peptide. Eur. J. Pharmacol. 427, 131-135 (2001).
59. Rassaf, T. et al. Circulating nitrite contributes to cardioprotection by remote ischemic preconditioning. Circ. Res. 114, 1601-1610 (2014).
60. Brzozowski, T. et al. Ischemic preconditioning of remote organs attenuates gastric ischemia-reperfusion injury through involvement of prostaglandins and sensory nerves. Eur. J. Pharmacol. 499, 201-213 (2004).
61. Hess, D. C., Hoda, M. N., Khan, M. B. Humoral mediators of remote ischemic conditioning: important role of eNOS/NO/nitrite. Acta Neurochir. Suppl. 121, 45-48 (2015).
62. Davidson, S. M. et al. Remote ischaemic preconditioning involves signalling through the SDF-1/CXCR4 signalling axis. Basic Res. Cardiol. 108, 377 (2013).
63. Cai, Z. P., Parajuli, N., Zheng, X., Becker, L. Remote ischemic preconditioning confers late protection against myocardial ischemia-reperfusion injury in mice by upregulating interleukin-10. Basic Res. Cardiol. 107, 277 (2012).
64. Li, J. et al. MicroRNA-144 is a circulating effector of remote ischemic preconditioning. Basic Res. Cardiol. 109, 423 (2014).
65. Kim-Shapiro, D. B., Gladwin, M. T. Mechanisms of nitrite bioactivation. Nitric Oxide 38, 58-68 (2014).
66. Liu, C. et al. Mechanisms of human erythrocytic bioactivation of nitrite. J. Biol. Chem. 290, 1281-1294 (2015).
67. Konstantinov, I. E. et al. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol. Genomics 19, 143-150 (2004).
68. Ong, S. B., Dongworth, R. K., Cabrera-Fuentes, H. A., Hausenloy, D. J. Role of the MPTP in conditioning the heart-translatability and mechanism. Br. J. Pharmacol. 172, 2074-2084 (2015).
69. Sun, J. et al. Protective effect of delayed remote limb ischemic postconditioning: role of mitochondrial KATP channels in a rat model of focal cerebral ischemic reperfusion injury. J. Cereb. Blood Flow Metab. 32, 851-859 (2012).
70. Shiva, S. Nitrite: a physiological store of nitric oxide and modulator of mitochondrial function. Redox Biol. 1, 40-44 (2013).
71. Shiva, S. et al. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J. Exp. Med. 204, 2089-2102 (2007).
72. Soriano, F. X. et al. Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability. J. Neurosci. 26, 4509-4518 (2006).
73. Celso Constantino, L., Tasca, C. I., Boeck, C. R. The role of NMDA receptors in the development of brain resistance through pre-and postconditioning. Aging Dis. 5, 430-441 (2014).
74. Shimizu, M., Konstantinov, I. E., Kharbanda, R. K., Cheung, M. H., Redington, A. N. Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs. Acta Physiol. (Oxf.) 190, 103-109 (2007).
75. Kono, Y. et al. Remote ischemic conditioning improves coronary microcirculation in healthy subjects and patients with heart failure. Drug Des. Devel. Ther. 8, 1175-1181 (2014).
76. Zhao, L., Nowak, T. S. Jr, CBF changes associated with focal ischemic preconditioning in the spontaneously hypertensive rat. J. Cereb. Blood Flow Metab. 26, 1128-1140 (2006).
77. Hoyte, L. C., Papadakis, M., Barber, P. A., Buchan, A. M. Improved regional cerebral blood flow is important for the protection seen in a mouse model of late phase ischemic preconditioning. Brain Res. 1121, 231-237 (2006).
78. Hoda, M. N. et al. Remote ischemic perconditioning is effective after embolic stroke in ovariectomized female mice. Transl. Stroke Res. 5, 484-490 (2014).
79. Hoda, M. N. et al. A 2 × 2 factorial design for the combination therapy of minocycline and remote ischemic perconditioning: efficacy in a preclinical trial in murine thromboembolic stroke model. Exp. Transl. Stroke Med. 6, 10 (2014).
80. Hoda, M. N. et al. Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. Stroke 43, 2794-2799 (2012).
81. Khan, M. B. et al. Remote ischemic postconditioning: harnessing endogenous protection in a murine model of vascular cognitive impairment. Transl. Stroke Res. 6, 69-77 (2015).
82. Meng, R. et al. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology 79, 1853-1861 (2012).
83. Curry, A. et al. Exercise pre-conditioning reduces brain inflammation in stroke via tumor necrosis factor-, extracellular signal-regulated kinase 1/2 and matrix metalloproteinase-9 activity. Neurol. Res. 32, 756-762 (2010).
84. Kloner, R. A., Speakman, M. T., Przyklenk, K. Ischemic preconditioning: a plea for rationally targeted clinical trials. Cardiovasc. Res. 55, 526-533 (2002).
85. Shinton, R., Sagar, G. Lifelong exercise and stroke. BMJ 307, 231-234 (1993).
86. Wannamethee, G., Shaper, A. G. Physical activity and stroke in British middle aged men. BMJ 304, 597-601 (1992).
87. Zhang, F., Wu, Y., Jia, J. Exercise preconditioning and brain ischemic tolerance. Neuroscience 177, 170-176 (2011).
88. Zhang, Q., Zhang, L., Yang, X., Wan, Y., Jia, J. The effects of exercise preconditioning on cerebral blood flow change and endothelin-1 expression after cerebral ischemia in rats. J. Stroke Cerebrovasc Dis. 23, 1696-1702 (2014).
89. Tomai, F. Warm up phenomenon and preconditioning in clinical practice. Heart 87, 99-100 (2002).
90. Kloner, R. A., Jennings, R. B. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1. Circulation 104, 2981-2989 (2001).
91. Kloner, R. A., Jennings, R. B. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation 104, 3158-3167 (2001).
92. Marber, M. S., Joy, M. D., Yellon, D. M. Is warm-up in angina ischaemic preconditioning Br. Heart J. 72, 213-215 (1994).
93. Tomai, F. et al. Mechanisms of the warm-up phenomenon. Eur. Heart J. 17, 1022-1027 (1996).
94. Williams, R. P., Manou-Stathopoulou, V., Redwood, S. R., Marber, M. S. 'Warm-up Angina': harnessing the benefits of exercise and myocardial ischaemia. Heart 100, 106-114 (2014).
95. Domenech, R., Macho, P., Schwarze, H., Sánchez, G. Exercise induces early and late myocardial preconditioning in dogs. Cardiovasc. Res. 55, 561-566 (2002).
96. Michelsen, M. M. et al. Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor. Basic Res. Cardiol. 107, 260 (2012).
97. Ren, C. et al. Remote ischemic post-conditioning reduced brain damage in experimental ischemia/reperfusion injury. Neurol. Res. 33, 514-519 (2011).
98. Ren, C., Gao, X., Steinberg, G. K., Zhao, H. Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning. Neuroscience 151, 1099-1103 (2008).
99. Ren, C. et al. Limb remote ischemic postconditioning protects against focal ischemia in rats. Brain Res. 1288, 88-94 (2009).
100. Hahn, C. D., Manlhiot, C., Schmidt, M. R., Nielsen, T. T., Redington, A. N. Remote ischemic per-conditioning: a novel therapy for acute stroke Stroke 42, 2960-2962 (2011).
101. Ren, C. et al. Limb remote ischemic per-conditioning in combination with post-conditioning reduces brain damage and promotes neuroglobin expression in the rat brain after ischemic stroke. Restor. Neurol. Neurosci. 33, 369-379 (2015).
102. Liu, X. et al. Remote ischemic postconditioning alleviates cerebral ischemic injury by attenuating endoplasmic reticulum stress-mediated apoptosis. Transl. Stroke Res. 5, 692-700 (2014).
103. Zhou, Y. et al. Remote limb ischemic postconditioning protects against neonatal hypoxic-ischemic brain injury in rat pups by the opioid receptor/Akt pathway. Stroke 42, 439-444 (2011).
104. Drunalini Perera, P. N. et al. Delayed remote ischemic postconditioning improves long term sensory motor deficits in a neonatal hypoxic ischemic rat model. PLoS ONE 9, e90258 (2014).
105. Xu, J. et al. Remote ischemic pre-and postconditioning improve postresuscitation myocardial and cerebral function in a rat model of cardiac arrest and resuscitation. Crit. Care Med. 43, e12-e18 (2015).
106. Dave, K. R., Saul, I., Prado, R., Busto, R., Perez-Pinzon, M. A. Remote organ ischemic preconditioning protect brain from ischemic damage following asphyxial cardiac arrest. Neurosci. Lett. 404, 170-175 (2006).
107. Jensen, H. A. et al. Remote ischemic preconditioning protects the brain against injury after hypothermic circulatory arrest. Circulation 123, 714-721 (2011).
108. Hougaard, K. D. et al. Remote ischemic perconditioning in thrombolysed stroke patients: randomized study of activating endogenous neuroprotection-design and MRI measurements. Int. J. Stroke 8, 141-146 (2013).
109. Hougaard, K. D. et al. Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial. Stroke 45, 159-167 (2014).
110. Geng, X. et al. Effect of remote ischemic postconditioning on an intracerebral hemorrhage stroke model in rats. Neurol. Res. 34, 143-148 (2012).
111. Fang, H. et al. CD36-mediated hematoma absorption following intracerebral hemorrhage: negative regulation by TLR4 signaling. J. Immunol. 192, 5984-5992 (2014).
112. Vaibhav, K. et al. Repeated remote ischemic conditioning (RIC) after intracerebral hemorrhage regulates macrophage polarization and CD36 expression to promote hematoma resolution [abstract]. Stroke 46, AWP253 (2015).
113. Nor, A. M. et al. Agreement between ambulance paramedic-and physician-recorded neurological signs with Face Arm Speech Test (FAST) in acute stroke patients. Stroke 35, 1355-1359 (2004).
114. Brandler, E. S., Sharma, M., Sinert, R. H., Levine, S. R. Prehospital stroke scales in urban environments: a systematic review. Neurology 82, 2241-2249 (2014).
115. You, J. S. et al. Predictive value of the Cincinnati Prehospital Stroke Scale for identifying thrombolytic candidates in acute ischemic stroke. Am. J. Emerg. Med. 31, 1699-1702 (2013).
116. Pérez de la Ossa, N. et al. Design and validation of a prehospital stroke scale to predict large arterial occlusion: the rapid arterial occlusion evaluation scale. Stroke 45, 87-91 (2014).
117. Qureshi, A. I. Acute hypertensive response in patients with stroke: pathophysiology and management. Circulation 118, 176-187 (2008).
118. Hess, D. C., Hoda, M. N., Bhatia, K. Remote limb perconditioning [corrected] and postconditioning: will it translate into a promising treatment for acute stroke Stroke 44, 1191-1197 (2013).
119. Saver, J. L., Gornbein, J. Treatment effects for which shift or binary analyses are advantageous in acute stroke trials. Neurology 72, 1310-1315 (2009).
120. Saver, J. L. et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N. Engl. J. Med. 372, 2285-2295 (2015).
121. Berkhemer, O. A., Majoie, C. B., Dippel, D. W., MR CLEAN Investigators. Endovascular therapy for ischemic stroke. N. Engl. J. Med. 372, 2363 (2015).
122. Gonzalez, N. R., Connolly, M., Dusick, J. R., Bhakta, H., Vespa, P. Phase I clinical trial for the feasibility and safety of remote ischemic conditioning for aneurysmal subarachnoid hemorrhage. Neurosurgery 75, 590-598 (2014).
123. Koch, S., Katsnelson, M., Dong, C., Perez-Pinzon, M. Remote ischemic limb preconditioning after subarachnoid hemorrhage: a phase Ib study of safety and feasibility. Stroke 42, 1387-1391 (2011).
124. Gonzalez, N. R. et al. Cerebral hemodynamic and metabolic effects of remote ischemic preconditioning in patients with subarachnoid hemorrhage. Acta Neurochir. Suppl. 115, 193-198 (2013).
125. Wang, Y. et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke 45, 663-669 (2014).
126. Chimowitz, M. I. et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N. Engl. J. Med. 365, 993-1003 (2011).
127. Holmstedt, C. A., Turan, T. N., Chimowitz, M. I. Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 12, 1106-1114 (2013).
128. Li, S. et al. Safety and feasibility of remote limb ischemic preconditioning in patients with unilateral middle cerebral artery stenosis and healthy volunteers. Cell Transplant. 24, 1901-1911 (2015).
129. Meng, R. et al. Ischemic conditioning is safe and effective for octo-and nonagenarians in stroke prevention and treatment. Neurotherapeutics 12, 667-677 (2015).
130. US National Library of Medicine. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT02534545 (2015).
131. Pérez-Pinzón, M. A., Alonso, O., Kraydieh, S., Dietrich, W. D. Induction of tolerance against traumatic brain injury by ischemic preconditioning. Neuroreport 10, 2951-2954 (1999).
132. Vaibhav, K., Baban, B., Khan, M. B., Liu, J. Y. Huo, Y., Hess, D. C., Dhandapani, K. M., Hoda, M. N. Remote ischemic preconditioning protects from traumatic brain injury (TBI) [abstract]. J. Neurotrauma 31, A87 (2014).
133. Vaibhav, K. et al. Remote ischemic conditioning (RIC) attenuates post-TBI ischemic injury and improves behavioral outcomes [abstract]. Stroke 46, ATP92 (2015).
134. Joseph, B. et al. Secondary brain injury in trauma patients: the effects of remote ischemic conditioning. J. Trauma Acute Care Surg. 78, 698-703 (2015).
135. Walsh, S. R. et al. Remote ischemic preconditioning for cerebral and cardiac protection during carotid endarterectomy: results from a pilot randomized clinical trial. Vasc. Endovascular Surg. 44, 434-439 (2010).
136. Iadecola, C. The pathobiology of vascular dementia. Neuron 80, 844-866 (2013).
137. Jellinger, K. A. Pathology and pathogenesis of vascular cognitive impairment-a critical update. Front. Aging Neurosci. 5, 17 (2013).
138. Gorelick, P. B. et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42, 2672-2713 (2011).
139. Iadecola, C. The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol. 120, 287-296 (2010).
140. Snyder, H. M. et al. Vascular contributions to cognitive impairment and dementia including Alzheimer's disease. Alzheimers Dement. 11, 710-717 (2015).
141. Poggesi, A. et al. 2001-2011: A decade of the LADIS (Leukoaraiosis And DISability) Study: what have we learned about white matter changes and small-vessel disease Cerebrovasc. Dis. 32, 577-588 (2011).
142. Bernbaum, M. et al. Reduced blood flow in normal white matter predicts development of leukoaraiosis. J. Cereb. Blood Flow Metab. 35, 1610-1615 (2015).
143. O'Sullivan, M. et al. Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis. Neurology 59, 321-326 (2002).
144. Verdelho, A. et al. Physical activity prevents progression for cognitive impairment and vascular dementia: results from the LADIS (Leukoaraiosis and Disability) study. Stroke 43, 3331-3335 (2012).
145. Bink, D. I., Ritz, K., Aronica, E., van der Weerd, L., Daemen, M. J. Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition. J. Cereb. Blood Flow Metab. 33, 1666-1684 (2013).
146. Shibata, M., Ohtani, R., Ihara, M., Tomimoto, H. White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke 35, 2598-2603 (2004).
147. Shibata, M. et al. Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. Stroke 38, 2826-2832 (2007).
148. Schmidt, R. et al. White matter lesion progression in LADIS: frequency, clinical effects, and sample size calculations. Stroke 43, 2643-2647 (2012).
149. US National Library of Medicine. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT02169739 (2014).
150. Johnsen, J., Pryds, K., Salman, R., Kristiansen, S. B., Botker, H. E. Optimizing the cardioprotective effects of remote ischemic preconditioning [Poster P2500]. Eur. Heart J. 35 (Suppl. 1), 444 (2014).
151. Przyklenk, K. Efficacy of cardioprotective 'conditioning' strategies in aging and diabetic cohorts: the co-morbidity conundrum. Drugs Aging 28, 331-343 (2011).
152. Sivaraman, V., Hausenloy, D. J., Wynne, A. M., Yellon, D. M. Preconditioning the diabetic human myocardium. J. Cell. Mol. Med. 14, 1740-1746 (2010).
153. Loukogeorgakis, S. P. et al. Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a KATP-channel dependent mechanism. Circulation 116, 1386-1395 (2007).
154. Simard, J. M. et al. Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage. J. Cereb. Blood Flow Metab. 29, 317-330 (2009).
155. Kottenberg, E. et al. Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting. J. Thorac Cardiovasc. Surg. 147, 376-382 (2014).
156. Kottenberg, E. et al. Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol-a clinical trial. Acta Anaesthesiol. Scand. 56, 30-38 (2012).
157. Meybohm, P. et al. A multicenter trial of remote ischemic preconditioning for heart surgery. N. Engl. J. Med. 373, 1397-1407 (2015).
158. Hausenloy, D. J. et al. Remote ischemic preconditioning and outcomes of cardiac surgery. N. Engl. J. Med. 373, 1408-1417 (2015).
159. Gidday, J. M. et al. Nitric oxide mediates cerebral ischemic tolerance in a neonatal rat model of hypoxic preconditioning. J. Cereb. Blood Flow Metab. 19, 331-340 (1999).
160. Orio, M. et al. Lipopolysaccharide induces early tolerance to excitotoxicity via nitric oxide and cGMP. Stroke 38, 2812-2817 (2007).
161. Gesuete, R., Kohama, S. G., Stenzel-Poore, M. P. Toll-like receptors and ischemic brain injury. J. Neuropathol. Exp. Neurol. 73, 378-386 (2014).
162. Sakata, H. et al. Interleukin 6-preconditioned neural stem cells reduce ischaemic injury in stroke mice. Brain 135, 3298-3310 (2012).
163. Digicaylioglu, M., Lipton, S. A. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-B signalling cascades. Nature 412, 641-647 (2001).
164. Pasha, Z. et al. Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovasc. Res. 77, 134-142 (2008).
165. Kapinya, K. J. et al. Tolerance against ischemic neuronal injury can be induced by volatile anesthetics and is inducible NO synthase dependent. Stroke 33, 1889-1898 (2002).
166. Zhao, P., Zuo, Z. Isoflurane preconditioning induces neuroprotection that is inducible nitric oxide synthase-dependent in neonatal rats. Anesthesiology 101, 695-703 (2004).
167. Ye, R. et al. Sevoflurane preconditioning improves mitochondrial function and long-term neurologic sequelae after transient cerebral ischemia: role of mitochondrial permeability transition. Crit. Care Med. 40, 2685-2693 (2012).
168. Peart, J. N., Gross, E. R., Gross, G. J. Opioid-induced preconditioning: recent advances and future perspectives. Vascul. Pharmacol. 42, 211-218 (2005).