Revisiting cerebral postischemic reperfusion injury: New insights in understanding reperfusion failure, hemorrhage, and edema

International Journal of Stroke

Volumn 10, Issue 2, 2015, Pages 143-152

  Bai, Jilin ^a   Lyden, Patrick D ^a  

^a CEDARS SINAI MEDICAL CENTER   (United States)

Author keywords

Acute; BBB; Hypothermia; Ischemic stroke; Recanalization; Reperfusion

Indexed keywords

ANTIOXIDANT; FINGOLIMOD; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE;

APOPTOSIS; ASTROCYTE; BLOOD BRAIN BARRIER; BLOOD CLOT LYSIS; BRAIN BLOOD FLOW; BRAIN CIRCULATION; BRAIN EDEMA; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; BRAIN NERVE CELL; BRAIN TISSUE; CELL INFILTRATION; CEREBRAL POSTISCHEMIC REPERFUSION INJURY; CONTRAST ENHANCEMENT; CORONARY ARTERY RECANALIZATION; DIFFUSION WEIGHTED IMAGING; DISEASE EXACERBATION; ENDOTHELIUM CELL; HUMAN; HYPOTHERMIA; ISCHEMIC POSTCONDITIONING; ISCHEMIC PRECONDITIONING; LEUKOCYTE; MICROGLIA; MICROTHROMBUS; NONHUMAN; OXIDATIVE STRESS; PERFUSION WEIGHTED IMAGING; PERICYTE; PRIORITY JOURNAL; PROTEIN SYNTHESIS; RECANALIZATION; REPERFUSION INJURY; REVIEW; THROMBOCYTE ACTIVATION; ANIMAL; PATHOLOGY; PATHOPHYSIOLOGY;

ANIMALS; BRAIN EDEMA; BRAIN ISCHEMIA; HUMANS; INTRACRANIAL HEMORRHAGES; REPERFUSION INJURY;

EID: 84921501321     PISSN: 17474930     EISSN: 17474949     Source Type: Journal    
DOI: 10.1111/ijs.12434     Document Type: Review

References (164)

1. Jauch EC, Saver JL, Adams HP etal. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44:870-947.
2. Towfighi A, Saver JL. Stroke declines from third to fourth leading cause of death in the United States: historical perspective and challenges ahead. Stroke 2011; 42:2351-2355.
3. Feigin VL, Forouzanfar MH, Krishnamurthi R etal. Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet 2014; 383:245-254.
4. Ovbiagele B, Goldstein LB, Higashida RT etal. Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke 2013; 44:2361-2375.
5. Hacke W, Kaste M, Bluhmki E etal. Thrombolysis with alteplase 3 to 4·5h after acute ischemic stroke. N Engl J Med 2008; 359:1317-1329.
6. Broderick JP, Palesch YY, Demchuk AM etal. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013; 368:893-903.
7. Ciccone A, Valvassori L, Nichelatti M etal. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013; 368:904-913.
8. Dalkara T, Arsava EM. Can restoring incomplete microcirculatory reperfusion improve stroke outcome after thrombolysis? J Cereb Blood Flow Metab 2012; 32:2091-2099.
9. Molina CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies. Stroke 2005; 36:2311-2320.
10. Yang GY, Betz AL. Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats. Stroke 1994; 25:1658-1664, discussion 1664-5.
11. Aronowski J, Strong R, Grotta JC. Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab 1997; 17:1048-1056.
12. Pan J, Konstas AA, Bateman B etal. Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology 2007; 49:93-102.
13. De Silva DA, Fink JN, Christensen S etal. Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET). Stroke 2009; 40:2872-2874.
14. Soares BP, Tong E, Hom J etal. Reperfusion is a more accurate predictor of follow-up infarct volume than recanalization: a proof of concept using CT in acute ischemic stroke patients. Stroke 2010; 41:e34-40.
15. Kloner RA. No-reflow phenomenon: maintaining vascular integrity. J Cardiovasc Pharmacol Ther 2011; 16:244-250.
16. Haley EC Jr, Lewandowski C, Tilley BC. Myths regarding the NINDS rt-PA Stroke Trial: setting the record straight. Ann Emerg Med 1997; 30:676-682.
17. Marler JR, Tilley BC, Lu M etal. Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology 2000; 55:1649-1655.
18. Christou I, Alexandrov AV, Burgin WS etal. Timing of recanalization after tissue plasminogen activator therapy determined by transcranial doppler correlates with clinical recovery from ischemic stroke. Stroke 2000; 31:1812-1816.
19. Anwar M, Buchweitz-Milton E, Weiss HR. Effect of prazosin on microvascular perfusion during middle cerebral artery ligation in the rat. Circ Res 1988; 63:27-34.
20. del Zoppo GJ, Schmid-Schonbein GW, Mori E etal. Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 1991; 22:1276-1283.
21. Belayev L, Pinard E, Nallet H etal. Albumin therapy of transient focal cerebral ischemia: in vivo analysis of dynamic microvascular responses. Stroke 2002; 33:1077-1084.
22. Garcia JH, Liu KF, Yoshida Y etal. Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat). Am J Pathol 1994; 145:728-740.
23. Garcia JH, Liu KF, Yoshida Y etal. Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am J Pathol 1994; 144:188-199.
24. Choudhri TF, Hoh BL, Zerwes HG etal. Reduced microvascular thrombosis and improved outcome in acute murine stroke by inhibiting GP IIb/IIIa receptor-mediated platelet aggregation. J Clin Invest 1998; 102:1301-1310.
25. Liu S, Connor J, Peterson S etal. Direct visualization of trapped erythrocytes in rat brain after focal ischemia and reperfusion. J Cereb Blood Flow Metab 2002; 22:1222-1230.
26. Okada Y, Copeland BR, Fitridge R etal. Fibrin contributes to microvascular obstructions and parenchymal changes during early focal cerebral ischemia and reperfusion. Stroke 1994; 25:1847-1853, discussion 1853-4.
27. Yemisci M, Gursoy-Ozdemir Y, Vural A etal. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med 2009; 15:1031-1037.
28. Krause GS, White BC, Aust SD etal. Brain cell death following ischemia and reperfusion: a proposed biochemical sequence. Crit Care Med 1988; 16:714-726.
29. Sato M, Hashimoto H, Kosaka F. Histological changes of neuronal damage in vegetative dogs induced by 18min of complete global brain ischemia: two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells. Acta Neuropathol 1990; 80:527-534.
30. Cooper HK, Zalewska T, Kawakami S etal. The effect of ischaemia and recirculation on protein synthesis in the rat brain. J Neurochem 1977; 28:929-934.
31. Wang X, Lo EH. Triggers and mediators of hemorrhagic transformation in cerebral ischemia. Mol Neurobiol 2003; 28:229-244.
32. Siesjo BK. Pathophysiology and treatment of focal cerebral ischemia. Part I: pathophysiology. J Neurosurg 1992; 77:169-184.
33. Chan PH, Kerlan R, Fishman RA. Reductions of gamma-aminobutyric acid and glutamate uptake and (Na++K+)-ATPase activity in brain slices and synaptosomes by arachidonic acid. J Neurochem 1983; 40:309-316.
34. Braughler JM. Lipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomes: protection by glucocorticoids. J Neurochem 1985; 44:1282-1288.
35. Nellgard B, Wieloch T. Postischemic blockade of AMPA but not NMDA receptors mitigates neuronal damage in the rat brain following transient severe cerebral ischemia. J Cereb Blood Flow Metab 1992; 12:2-11.
36. White BC, Sullivan JM, DeGracia DJ etal. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci 2000; 179(S1-2):1-33.
37. Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 1973; 134:707-716.
38. Saito A, Maier CM, Narasimhan P etal. Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Mol Neurobiol 2005; 31:105-116.
39. Li J, Ma X, Yu W etal. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats. PLoS ONE 2012; 7:e46498.
40. Chan PH. Oxygen radicals in focal cerebral ischemia. Brain Pathol 1994; 4:59-65.
41. Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 2001; 21:2-14.
42. Schild L, Reiser G. Oxidative stress is involved in the permeabilization of the inner membrane of brain mitochondria exposed to hypoxia/reoxygenation and low micromolar Ca2+. FEBS J 2005; 272:3593-3601.
43. Yang G, Chan PH, Chen J etal. Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. Stroke 1994; 25:165-170.
44. Fujimura M, Morita-Fujimura Y, Noshita N etal. The cytosolic antioxidant copper/zinc-superoxide dismutase prevents the early release of mitochondrial cytochrome c in ischemic brain after transient focal cerebral ischemia in mice. J Neurosci 2000; 20:2817-2824.
45. Noshita N, Sugawara T, Fujimura M etal. Manganese superoxide dismutase affects cytochrome c release and Caspase-9 activation after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 2001; 21:557-567.
46. Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996; 271(5 Pt 1):C1424-1437.
47. Didion SP, Ryan MJ, Baumbach GL etal. Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen. Am J Physiol Heart Circ Physiol 2002; 283:H1569-1576.
48. Iadecola C, Zhang F, Niwa K etal. SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat Neurosci 1999; 2:157-161.
49. Baumbach GL, Didion SP, Faraci FM. Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase. Stroke 2006; 37:1850-1855.
50. Tsujimoto Y, Nakagawa T, Shimizu S. Mitochondrial membrane permeability transition and cell death. Biochim Biophys Acta 2006; 1757:1297-1300.
51. Kristal BS, Dubinsky JM. Mitochondrial permeability transition in the central nervous system: induction by calcium cycling-dependent and -independent pathways. J Neurochem 1997; 69:524-538.
52. Kobayashi T, Kuroda S, Tada M etal. Calcium-induced mitochondrial swelling and cytochrome c release in the brain: its biochemical characteristics and implication in ischemic neuronal injury. Brain Res 2003; 960:62-70.
53. Solenski NJ, diPierro CG, Trimmer PA etal. Ultrastructural changes of neuronal mitochondria after transient and permanent cerebral ischemia. Stroke 2002; 33:816-824.
54. Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem 2010; 47:69-84.
55. Yin W, Signore AP, Iwai M etal. Rapidly increased neuronal mitochondrial biogenesis after hypoxic-ischemic brain injury. Stroke 2008; 39:3057-3063.
56. Zhang Q, Wu Y, Zhang P etal. Exercise induces mitochondrial biogenesis after brain ischemia in rats. Neuroscience 2012; 205:10-17.
57. Stetler RA, Leak RK, Yin W etal. Mitochondrial biogenesis contributes to ischemic neuroprotection afforded by LPS pre-conditioning. J Neurochem 2012; 123(Suppl. 2):125-137.
58. Kleihues P, Hossmann KA. Protein synthesis in the cat brain after prolonged cerebral ischemia. Brain Res 1971; 35:409-418.
59. DeGracia DJ, Neumar RW, White BC, Krause GS. Global brain ischemia and reperfusion: modifications in eukaryotic initiation factors associated with inhibition of translation initiation. J Neurochem 1996; 67:2005-2012.
60. Hu BR, Janelidze S, Ginsberg MD etal. Protein aggregation after focal brain ischemia and reperfusion. J Cereb Blood Flow Metab 2001; 21:865-875.
61. Kumar R, Azam S, Sullivan JM etal. Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK. J Neurochem 2001; 77:1418-1421.
62. Herdegen T, Claret FX, Kallunki T etal. Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N-terminal kinases after neuronal injury. J Neurosci 1998; 18:5124-5135.
63. DeGracia DJ, Kumar R, Owen CR etal. Molecular pathways of protein synthesis inhibition during brain reperfusion: implications for neuronal survival or death. J Cereb Blood Flow Metab 2002; 22:127-141.
64. Pain VM. Initiation of protein synthesis in eukaryotic cells. Eur J Biochem 1996; 236:747-771.
65. Roy B, Lee AS. The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex. Nucleic Acids Res 1999; 27:1437-1443.
66. MacManus JP, Buchan AM. Apoptosis after experimental stroke: fact or fashion? J Neurotrauma 2000; 17:899-914.
67. Zhang F, Yin W, Chen J. Apoptosis in cerebral ischemia: executional and regulatory signaling mechanisms. Neurol Res 2004; 26:835-845.
68. Chelluboina B, Klopfenstein JD, Gujrati M etal. Temporal regulation of apoptotic and anti-apoptotic molecules after middle cerebral artery occlusion followed by reperfusion. Mol Neurobiol 2014; 49:50-65.
69. Nakka VP, Gusain A, Mehta SL, Raghubir R. Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities. Mol Neurobiol 2008; 37:7-38.
70. Slevin M, Krupinski J, Kumar P etal. Gene activation and protein expression following ischaemic stroke: strategies towards neuroprotection. J Cell Mol Med 2005; 9:85-102.
71. del Zoppo GJ. The role of platelets in ischemic stroke. Neurology 1998; 51(3 Suppl. 3):S9-14.
72. Kleinschnitz C, Pozgajova M, Pham M etal. Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation 2007; 115:2323-2330.
73. Adams HP Jr, Effron MB, Torner J etal. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II). Stroke 2008; 39:87-99.
74. Elvers M, Stegner D, Hagedorn I etal. Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1. Sci Signal 2010; 3:ra1.
75. Kleinschnitz C, De Meyer SF, Schwarz T etal. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood 2009; 113:3600-3603.
76. Thomas A, Gasque P, Vaudry D etal. Expression of a complete and functional complement system by human neuronal cells in vitro. Int Immunol 2000; 12:1015-1023.
77. Nishino H, Czurko A, Fukuda A etal. Pathophysiological process after transient ischemia of the middle cerebral artery in the rat. Brain Res Bull 1994; 35:51-56.
78. Kato H, Kogure K, Liu XH etal. Progressive expression of immunomolecules on activated microglia and invading leukocytes following focal cerebral ischemia in the rat. Brain Res 1996; 734:203-212.
79. Huang J, Kim LJ, Mealey R etal. Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein. Science 1999; 285:595-599.
80. Arumugam TV, Woodruff TM, Lathia JD etal. Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience 2009; 158:1074-1089.
81. Hallenbeck JM, Dutka AJ, Tanishima T etal. Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. Stroke 1986; 17:246-253.
82. Bednar MM, Raymond S, McAuliffe T etal. The role of neutrophils and platelets in a rabbit model of thromboembolic stroke. Stroke 1991; 22:44-50.
83. Matsuo Y, Onodera H, Shiga Y etal. Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 1994; 25:1469-1475.
84. Hurn PD, Subramanian S, Parker SM etal. T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab 2007; 27:1798-1805.
85. Kleinschnitz C, Schwab N, Kraft P etal. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood 2010; 115:3835-3842.
86. Yilmaz G, Arumugam TV, Stokes KY, Granger DN. Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 2006; 113:2105-2112.
87. Becker K, Kindrick D, Relton J etal. Antibody to the alpha4 integrin decreases infarct size in transient focal cerebral ischemia in rats. Stroke 2001; 32:206-211.
88. Relton JK, Sloan KE, Frew EM etal. Inhibition of alpha4 integrin protects against transient focal cerebral ischemia in normotensive and hypertensive rats. Stroke 2001; 32:199-205.
89. Liesz A, Zhou W, Mracsko E etal. Inhibition of lymphocyte trafficking shields the brain against deleterious neuroinflammation after stroke. Brain 2011; 134(Pt 3):704-720.
90. Kleinschnitz C, Kraft P, Dreykluft A etal. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood 2013; 121:679-691.
91. Belayev L, Busto R, Zhao W, Ginsberg MD. Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 1996; 739:88-96.
92. Rosenberg GA, Estrada EY, Dencoff JE. Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke 1998; 29:2189-2195.
93. del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia. J Cereb Blood Flow Metab 2003; 23:879-894.
94. Kahles T, Luedike P, Endres M etal. NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke 2007; 38:3000-3006.
95. Gu Y, Dee CM, Shen J. Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood-brain barrier permeability. Front Biosci (Schol Ed) 2011; 3:1216-1231.
96. Betz AL, Coester HC. Effect of steroids on edema and sodium uptake of the brain during focal ischemia in rats. Stroke 1990; 21:1199-1204.
97. Kuroiwa T, Ting P, Martinez H, Klatzo I. The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion. Acta Neuropathol 1985; 68:122-129.
98. Abo-Ramadan U, Durukan A, Pitkonen M etal. Post-ischemic leakiness of the blood-brain barrier: a quantitative and systematic assessment by Patlak plots. Exp Neurol 2009; 219:328-333.
99. Strbian D, Durukan A, Pitkonen M etal. The blood-brain barrier is continuously open for several weeks following transient focal cerebral ischemia. Neuroscience 2008; 153:175-181.
100. Rosenberg GA, Kornfeld M, Estrada E etal. TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase. Brain Res 1992; 576:203-207.
101. Hamann GF, Liebetrau M, Martens H etal. Microvascular basal lamina injury after experimental focal cerebral ischemia and reperfusion in the rat. J Cereb Blood Flow Metab 2002; 22:526-533.
102. Yang Y, Estrada EY, Thompson JF etal. Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab 2007; 27:697-709.
103. Gidday JM, Gasche YG, Copin JC etal. 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:H558-568.
104. Garbuzova-Davis S, Rodrigues MC, Hernandez-Ontiveros DG etal. Blood-brain barrier alterations provide evidence of subacute diaschisis in an ischemic stroke rat model. PLoS ONE 2013; 8:e63553.
105. Chen B, Friedman B, Cheng Q etal. Severe blood-brain barrier disruption and surrounding tissue injury. Stroke 2009; 40:e666-674.
106. Winkler EA, Bell RD, Zlokovic BV. Central nervous system pericytes in health and disease. Nat Neurosci 2011; 14:1398-1405.
107. Reggiori F, Klionsky DJ. Autophagy in the eukaryotic cell. Eukaryot Cell 2002; 1:11-21.
108. Liu J, Wang Y, Akamatsu Y etal. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials. Prog Neurobiol 2014; 115:138-156.
109. Swanson RA, Ying W, Kauppinen TM. Astrocyte influences on ischemic neuronal death. Curr Mol Med 2004; 4:193-205.
110. Hayakawa K, Pham LD, Katusic ZS etal. Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery. Proc Natl Acad Sci U S A 2012; 109:7505-7510.
111. Li M, Sun L, Li Y etal. Oxygen glucose deprivation/reperfusion astrocytes promotes primary neural stem/progenitor cell proliferation by releasing high-mobility group box 1. Neurochem Res 2014; 39:1440-1450.
112. Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 2009; 158:1021-1029.
113. Pal G, Lovas G, Dobolyi A. Induction of transforming growth factor beta receptors following focal ischemia in the rat brain. PLoS ONE 2014; 9:e106544.
114. Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol 2006; 147(Suppl. 1):S232-240.
115. Rami A, Langhagen A, Steiger S. Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death. Neurobiol Dis 2008; 29:132-141.
116. Chen B, Friedman B, Whitney MA etal. Thrombin activity associated with neuronal damage during acute focal ischemia. J Neurosci 2012; 32:7622-7631.
117. Rajput PS, Lyden PD, Chen B etal. Protease activated receptor-1 mediates cytotoxicity during ischemia using in vivo and in vitro models. Neuroscience 2014; 281c:229-240.
118. Tisserand M, Naggara O, Legrand L etal. Patient 'candidate' for thrombolysis: MRI is essential. Diagn Interv Imaging 2014; 95:1135-1144.
119. Nour M, Scalzo F, Liebeskind DS. Ischemia-reperfusion injury in stroke. Interv Neurol 2013; 1:185-199.
120. Neumann-Haefelin T, Kastrup A, de Crespigny A etal. Serial MRI after transient focal cerebral ischemia in rats: dynamics of tissue injury, blood-brain barrier damage, and edema formation. Stroke 2000; 31:1965-1972, discussion 1972-3.
121. Olah L, Wecker S, Hoehn M. Secondary deterioration of apparent diffusion coefficient after 1-hour transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab 2000; 20:1474-1482.
122. Sundt TM Jr, Waltz AG. Cerebral ischemia and reactive hyperemia. Studies of cortical blood flow and microcirculation before, during, and after temporary occlusion of middle cerebral artery of squirrel monkeys. Circ Res 1971; 28:426-433.
123. Heiss WD, Graf R, Lottgen J etal. Repeat positron emission tomographic studies in transient middle cerebral artery occlusion in cats: residual perfusion and efficacy of postischemic reperfusion. J Cereb Blood Flow Metab 1997; 17:388-400.
124. Tamura A, Asano T, Sano K. Correlation between rCBF and histological changes following temporary middle cerebral artery occlusion. Stroke 1980; 11:487-493.
125. Schaller B, Graf R. Cerebral ischemia and reperfusion: the pathophysiologic concept as a basis for clinical therapy. J Cereb Blood Flow Metab 2004; 24:351-371.
126. Kidwell CS, Saver JL, Mattiello J etal. Diffusion-perfusion MRI characterization of post-recanalization hyperperfusion in humans. Neurology 2001; 57:2015-2021.
127. Warach S, Latour LL. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption. Stroke 2004; 35(11 Suppl. 1):2659-2661.
128. Schaller B, Graf R. Cerebral ischemic preconditioning. An experimental phenomenon or a clinical important entity of stroke prevention? J Neurol 2002; 249:1503-1511.
129. Dirnagl U, Simon RP, Hallenbeck JM. Ischemic tolerance and endogenous neuroprotection. Trends Neurosci 2003; 26:248-254.
130. Weih M, Kallenberg K, Bergk A etal. Attenuated stroke severity after prodromal TIA: a role for ischemic tolerance in the brain? Stroke 1999; 30:1851-1854.
131. Wegener S, Gottschalk B, Jovanovic V etal. Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study. Stroke 2004; 35:616-621.
132. Sitzer M, Foerch C, Neumann-Haefelin T etal. Transient ischaemic attack preceding anterior circulation infarction is independently associated with favourable outcome. J Neurol Neurosurg Psychiatry 2004; 75:659-660.
133. Glantz L, Avramovich A, Trembovler V etal. Ischemic preconditioning increases antioxidants in the brain and peripheral organs after cerebral ischemia. Exp Neurol 2005; 192:117-124.
134. Perez-Pinzon MA, Dave KR, Raval AP. Role of reactive oxygen species and protein kinase C in ischemic tolerance in the brain. Antioxid Redox Signal 2005; 7:1150-1157.
135. Chen J, Graham SH, Zhu RL, Simon RP. Stress proteins and tolerance to focal cerebral ischemia. J Cereb Blood Flow Metab 1996; 16:566-577.
136. Belayev L, Ginsberg MD, Alonso OF etal. Bilateral ischemic tolerance of rat hippocampus induced by prior unilateral transient focal ischemia: relationship to c-fos mRNA expression. Neuroreport 1996; 8:55-59.
137. Puisieux F, Deplanque D, Bulckaen H etal. Brain ischemic preconditioning is abolished by antioxidant drugs but does not up-regulate superoxide dismutase and glutathion peroxidase. Brain Res 2004; 1027:30-37.
138. Rosenzweig HL, Lessov NS, Henshall DC etal. Endotoxin preconditioning prevents cellular inflammatory response during ischemic neuroprotection in mice. Stroke 2004; 35:2576-2581.
139. Nakatsuka H, Ohta S, Tanaka J etal. Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils. Neurosci Lett 2000; 278:53-56.
140. Yano S, Morioka M, Fukunaga K etal. Activation of Akt/protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus. J Cereb Blood Flow Metab 2001; 21:351-360.
141. Yin XH, Zhang QG, Miao B, Zhang G. Neuroprotective effects of preconditioning ischaemia on ischaemic brain injury through inhibition of mixed-lineage kinase 3 via NMDA receptor-mediated Akt1 activation. J Neurochem 2005; 93:1021-1029.
142. Dirnagl U, Becker K, Meisel A. Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol 2009; 8:398-412.
143. Kapinya KJ, Prass K, Dirnagl U. Isoflurane induced prolonged protection against cerebral ischemia in mice: a redox sensitive mechanism? Neuroreport 2002; 13:1431-1435.
144. Lucchinetti E, Ambrosio S, Aguirre J etal. Sevoflurane inhalation at sedative concentrations provides endothelial protection against ischemia-reperfusion injury in humans. Anesthesiology 2007; 106:262-268.
145. Zhao H, Sapolsky RM, Steinberg GK. Interrupting reperfusion as a stroke therapy: ischemic postconditioning reduces infarct size after focal ischemia in rats. J Cereb Blood Flow Metab 2006; 26:1114-1121.
146. Liang J, Luan Y, Lu B etal. Protection of ischemic postconditioning against neuronal apoptosis induced by transient focal ischemia is associated with attenuation of NF-kappaB/p65 activation. PLoS ONE 2014; 9:e96734.
147. Zhang RL, Chopp M, Jiang N etal. Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke 1995; 26:1438-1442, discussion 1443.
148. Reddy MK, Labhasetwar V. Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury. FASEB J 2009; 23:1384-1395.
149. Kahles T, Brandes RP. Which NADPH oxidase isoform is relevant for ischemic stroke? The case for nox 2. Antioxid Redox Signal 2013; 18:1400-1417.
150. Diener HC, Lees KR, Lyden P etal. NXY-059 for the treatment of acute stroke: pooled analysis of the SAINT I and II Trials. Stroke 2008; 39:1751-1758.
151. Kahles T, Brandes RP. NADPH oxidases as therapeutic targets in ischemic stroke. Cell Mol Life Sci 2012; 69:2345-2363.
152. Wei Y, Yemisci M, Kim HH etal. Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol 2011; 69:119-129.
153. Man K, Ng KT, Lee TK etal. FTY720 attenuates hepatic ischemia-reperfusion injury in normal and cirrhotic livers. Am J Transplant 2005; 5:40-49.
154. Delbridge MS, Shrestha BM, Raftery A etal. Reduction of ischemia-reperfusion injury in the rat kidney by FTY720, a synthetic derivative of sphingosine. Transplantation 2007; 84:187-195.
155. Kaudel CP, Frink M, Schmiddem U etal. FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia; impact on long-term survival and T-lymphocyte tissue infiltration. Transplant Proc 2007; 39:499-502.
156. Awad AS, Ye H, Huang L etal. Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney. Am J Physiol Renal Physiol 2006; 290:F1516-1524.
157. Ishikawa M, Sekizuka E, Sato S etal. Effects of moderate hypothermia on leukocyte- endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion. Stroke 1999; 30:1679-1686.
158. 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; 31:1982-1989, discussion 1989.
159. Krieger DW, De Georgia MA, Abou-Chebl A etal. Cooling for acute ischemic brain damage (cool aid): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke 2001; 32:1847-1854.
160. Lyden PD, Allgren RL, Ng K etal. Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience. J Stroke Cerebrovasc Dis 2005; 14:107-114.
161. Song SS, Lyden PD. Overview of therapeutic hypothermia. Curr Treat Options Neurol 2012; 14:541-548.
162. Guluma KZ, Oh H, Yu SW etal. Effect of endovascular hypothermia on acute ischemic edema: morphometric analysis of the ICTuS trial. Neurocrit Care 2008; 8:42-47.
163. Zgavc T, Ceulemans AG, Sarre S etal. Experimental and clinical use of therapeutic hypothermia for ischemic stroke: opportunities and limitations. Stroke Res Treat 2011; 2011:689290.
164. Huang F, Zhou L. Effect of mild hypothermia on the changes of cerebral blood flow, brain blood barrier and neuronal injuries following reperfusion of focal cerebral ischemia in rats. Chin Med J (Engl) 1998; 111:368-372.