Herbal medicines for ischemic stroke: Combating inflammation as therapeutic targets

Journal of Neuroimmune Pharmacology

Volumn 9, Issue 3, 2014, Pages 313-339

  Gu, Yong ^a,b   Chen, Jianping ^a   Shen, Jiangang ^a,b  

^a THE UNIVERSITY OF HONG KONG   (Hong Kong)

^b UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

Herbal medicine; Inflammation; Inflammatory factors; Ischemic stroke; Neuroprotection

Indexed keywords

ALKALOID DERIVATIVE; CHEMOKINE; CYTOKINE; FREE RADICAL; HERBACEOUS AGENT; NATURAL PRODUCT; PHENOL DERIVATIVE; SAPONIN DERIVATIVE; TERPENOID DERIVATIVE; AUTACOID; NEUROPROTECTIVE AGENT; PLANT MEDICINAL PRODUCT;

ANTIINFLAMMATORY ACTIVITY; ASTROCYTE; BRAIN DAMAGE; BRAIN EDEMA; BRAIN ISCHEMIA; BRAIN PERICYTE; CELL INFILTRATION; CHINESE MEDICINE; DRUG TARGETING; ENDOTHELIUM CELL; HERBAL MEDICINE; HUMAN; IMMUNOCOMPETENT CELL; INFLAMMATION; MICROGLIA; NERVE CELL NETWORK; NEUROPROTECTION; NONHUMAN; OCCLUSIVE CEREBROVASCULAR DISEASE; PRIORITY JOURNAL; REVIEW; TISSUE REPAIR; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG DELIVERY SYSTEM; IMMUNOLOGY; PROCEDURES; STROKE;

ANIMALS; BRAIN ISCHEMIA; DRUG DELIVERY SYSTEMS; HERBAL MEDICINE; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; NEUROPROTECTIVE AGENTS; PLANT PREPARATIONS; STROKE;

EID: 84901269295     PISSN: 15571890     EISSN: 15571904     Source Type: Journal    
DOI: 10.1007/s11481-014-9525-5     Document Type: Review

References (257)

1. Neuroprotection: the end of an era? Lancet 368:1548.
2. Abulafia DP, de Rivero Vaccari JP, Lozano JD, Lotocki G, Keane RW, Dietrich WD (2009) Inhibition of the inflammasome complex reduces the inflammatory response after thromboembolic stroke in mice. J Cereb Blood Flow Metab 29:534-544
3. Aguzzi A, Barres B, Bennett ML (2013) Microglia: scapegoat, saboteur, or something else? Science 339:156-161
4. Albert D, Zundorf I, Dingermann T, Muller WE, Steinhilber D, Werz O (2002) Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem Pharmacol 64:1767-1775 (Pubitemid 35355728)
5. Al-Majed AA, Al-Omar FA, Nagi MN (2006) Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus. Eur J Pharm 543:40-47 (Pubitemid 44092699)
6. Aloe L, Rocco ML, Bianchi P, Manni L (2012) Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med 10:239-244
7. Andsberg G, Kokaia Z, Klein RL, Muzyczka N, Lindvall O, Mandel RJ (2002) Neuropathological and behavioral consequences of adeno-associated viral vector-mediated continuous intrastriatal neurotrophin delivery in a focal ischemia model in rats. Neurobiol Dis 9:187-204 (Pubitemid 34261214)
8. Atianand MK, Rathinam VA, Fitzgerald KA (2013) SnapShot: inflammasomes. Cell 153(272-272):e271
9. Bai F, Xu Y, Chen J, Liu Q, Gu J, Wang X, Ma J, Li H, Onuchic JN, Jiang H (2013) Free energy landscape for the binding process of huperzine a to acetylcholinesterase. Proc Natl Acad Sci U S A 110:4273-4278
10. Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, Lysko PG, Feuerstein GZ (1997) Tumor necrosis factor-alpha - a mediator of focal ischemic brain injury. Stroke 28:1233-1244 (Pubitemid 27248902)
11. Bohacek I, Cordeau P, Lalancette-Hebert M, Gorup D, Weng YC, Gajovic S, Kriz J (2012) Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury. J Neuroinflammation 9:191
12. Borutaite V, Toleikis A, Brown GC (2013) In the eye of the storm: mitochondrial damage during heart and brain ischaemia. FEBS J 280:4999-5014
13. Boutin H, LeFeuvre RA, Horai R, Asano M, Iwakura Y, Rothwell NJ (2001) Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci 21:5528-5534 (Pubitemid 32692151)
14. Brait VH, Arumugam TV, Drummond GR, Sobey CG (2012) Importance of T lymphocytes in brain injury, immunodeficiency, and recovery after cerebral ischemia. J Cereb Blood F Metab 32:598-611
15. Brambilla R, Couch Y, Lambertsen KL (2013) The effect of stroke on immune function. Mol Cell Neurosci 53:26-33
16. Breckwoldt MO, Chen JW, Stangenberg L, Aikawa E, Rodriguez E, Qiu SM, Moskowitz MA, Weissleder R (2008) Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci U S A 105:18584-18589
17. Burnstock G (2008) Purinergic signalling and disorders of the central nervous system. Nat Rev Drug Discov 7:575-590
18. Cai F, Li CR, Wu JL, Chen JG, Liu C, Min Q, Yu W, Ouyang CH, Chen JH (2006) Theaflavin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-inflammatory effect and modulation of STAT-1. Mediat Inflamm 2006:30490
19. Campanella M, Sciorati C, Tarozzo G, Beltramo M (2002) Flow cytometric analysis of inflammatory cells in ischemic rat brain. Stroke 33:586-592 (Pubitemid 34123411)
20. Carden DL, Granger DN (2000) Pathophysiology of ischaemia-reperfusion injury. J Pathol 190:255-266 (Pubitemid 30141372)
21. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang DR, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917-924 (Pubitemid 43980506)
22. Castello-Ruiz M, Torregrosa G, Burguete MC, Salom JB, Gil JV, Miranda FJ, Jover-Mengual T, Marrachelli VG, Alborch E (2011) Soy-derived phytoestrogens as preventive and acute neuroprotectors in experimental ischemic stroke: influence of rat strain. Phytomedicine 18:513-515
23. Cha JK, Jeong MH, Kim EK, Lim YJ, Ha BR, Kim SH, Kim JW (2002) Surface expression of P-selectin on platelets is related with clinical worsening in acute ischemic stroke. J Korean Med Sci 17:811-816
24. Cha JK, Jeong MH, Jang JY, Bae HR, Lim YJ, Kim JS, Kim SH, Kim JW (2003) Serial measurement of surface expressions of CD63, P-selectin and CD40 ligand on platelets in atherosclerotic ischernic stroke - a possible role of CD40 ligand on platelets in atherosclerotic ischemic stroke. Cerebrovasc Dis 16:376-382
25. Checker R, Patwardhan RS, Sharma D, Menon J, Thoh M, Bhilwade HN, Konishi T, Sandur SK (2012) Schisandrin B exhibits anti-inflammatory activity through modulation of the redox-sensitive transcription factors Nrf2 and NF-kappa B. Free Rad Biol Med 53:1421-1430
26. Chen YF (2012) Traditional Chinese herbal medicine and cerebral ischemia. Front Biosci (Elite Ed) 4:809-817
27. Chen GY, Nunez G (2010) Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol 10:826-837
28. Chen YH, Du GH, Zhang JT (2000) Salvianolic acid B protects brain against injuries caused by ischemia-reperfusion in rats. Acta Pharmacol Sin 21:463-466
29. Chen Y, Hallenbeck JM, Ruetzler C, Bol D, Thomas K, Berman NEJ, Vogel SN (2003) Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates ischemic brain injury and is associated with recruitment of inflammatory cells. J Cereb Blood F Metab 23:748-755 (Pubitemid 36713680)
30. Chen Y, Wu X, Yu S, Lin X, Wu J, Li L, Zhao J, Zhao Y (2012) Neuroprotection of tanshinone IIA against cerebral ischemia/reperfusion injury through inhibition of macrophage migration inhibitory factor in rats. PLoS One 7:e40165
31. Cherubini A, Polidori MC, Bregnocchi M, Pezzuto S, Cecchetti R, Ingegni T, di Iorio A, Senin U, Mecocci P (2000) Antioxidant profile and early outcome in stroke patients. Stroke 31:2295-2300
32. Cho J, Lee HK (2004) Wogonin inhibits ischemic brain injury in a rat model of permanent middle cerebral artery occlusion. Biol Pharm Bull 27:1561-1564 (Pubitemid 41701639)
33. Chou MY, Hartvigsen K, Hansen LF, Fogelstrand L, Shaw PX, Boullier A, Binder CJ, Witztum JL (2008) Oxidation-specific epitopes are important targets of innate immunity. J Intern Med 263:479-488 (Pubitemid 351533561)
34. Cipriani R, Villa P, Chece G, Lauro C, Paladini A, Micotti E, Perego C, De Simoni MG, Fredholm BB, Eusebi F, Limatola C (2011) CX3CL1 is neuroprotective in permanent focal cerebral ischemia in rodents. J Neurosci 31:16327-16335
35. Clark WM, Rinker LG, Lessov NS, Hazel K, Hill JK, Stenzel-Poore M, Eckenstein F (2000) Lack of interleukin-6 expression is not protective against focal central nervous system ischemia. Stroke 31:1715-1720 (Pubitemid 30437528)
36. Clausen BH, Lambertsen KL, Meldgaard M, Finsen B (2005) A quantitative in situ hybridization and polymerase chain reaction study of microglial-macrophage expression of interleukin-1β mRNA following permanent middle cerebral artery occlusion in mice. Neuroscience 132:879-892 (Pubitemid 40602524)
37. Connolly ES Jr,Winfree CJ, Springer TA, Naka Y, Liao H, Yan SD, Stern DM, Solomon RA, Gutierrez-Ramos JC, Pinsky DJ (1996) Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke. J Clin Invest 97:209-216 (Pubitemid 26021710)
38. Connolly ES,Winfree CJ, Prestigiacomo CJ, Kim SC, Choudhri TF, Hoh BL, Naka Y, Solomon RA, Pinsky DJ (1997) Exacerbation of cerebral injury in mice that express the P-selectin gene - identification of P-selectin blockade as a new target for the treatment of stroke. Circ Res 81:304-310 (Pubitemid 27362516)
39. Dada LA, Sznajder JI (2011) Mitochondrial Ca(2)+ and ROS take center stage to orchestrate TNF-alpha-mediated inflammatory responses. J Clin Invest 121:1683-1685
40. de Bilbao F, Arsenijevic D, Moll T, Garcia-Gabay I, Vallet P, Langhans W, Giannakopoulos P (2009) In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice. J Neurochem 110:12-22
41. Delzoppo GJ (1994) Microvascular changes during cerebral-ischemia and reperfusion. Cerebrovas Brain Metab 6:47-96
42. Delzoppo GJ, Schmidschonbein GW, Mori E, Copeland BR, Chang CM (1991) Polymorphonuclear leukocytes occlude capillaries following middle cerebral-artery occlusion and reperfusion in baboons. Stroke 22:1276-1283
43. Denes A, Vidyasagar R, Feng J, Narvainen J, McColl BW, Kauppinen RA, Allan SM (2007) Proliferating resident microglia after focal cerebral ischaemia in mice. J Cereb Blood Flow Metab 27:1941-1953 (Pubitemid 350129163)
44. Deroide N, Li X, Lerouet D, Van Vre E, Baker L, Harrison J, Poittevin M, Masters L, Nih L, Margaill I, Iwakura Y, Ryffel B, Pocard M, Tedgui A, Kubis N, Mallat Z (2013) MFGE8 inhibits inflammasome-induced IL-1beta production and limits postischemic cerebral injury. J Clin Invest 123:1176-1181
45. Di Giacomo C, Acquaviva R, Santangelo R, Sorrenti V, Vanella L, Li Volti G, D'Orazio N, Vanella A, Galvano F (2012) Effect of Treatment with Cyanidin-3-O-beta-D-Glucoside on Rat Ischemic/Reperfusion Brain Damage. Evid Based Complement Alternat Med 2012:285750
46. Di Virgilio F, Ceruti S, Brarnanti P, Abbracchio MP (2009) Purinergic signalling in inflammation of the central nervous system. Trends Neurosci 32:79-87
47. Dong L, Qiao H, Zhang X, Wang C, Wang L, Cui L, Zhao J, Xing Y, Li Y, Liu Z, Zhu C (2013) Parthenolide is neuroprotective in rat experimental stroke model: downregulating NF-kappaB, phosphop38MAPK, and caspase-1 and ameliorating BBB permeability. Mediat Inflamm 2013:370804
48. Du H, Xiang J, Zhang Y, Tang Y (2007) A spectroscopic and molecular modeling study of sinomenine binding to transferrin. Bioorg Med Chem Lett 17:1701-1704
49. Eggen BJ, Raj D, Hanisch UK, Boddeke HW (2013) Microglial phenotype and adaptation. J Neuroimmune Pharmacol 8:807-823
50. Eisenberg DM, Harris ES, Littlefield BA, Cao S, Craycroft JA, Scholten R, Bayliss P, Fu Y, Wang W, Qiao Y, Zhao Z, Chen H, Liu Y, Kaptchuk T, Hahn WC, Wang X, Roberts T, Shamu CE, Clardy J (2011) Developing a library of authenticated Traditional Chinese Medicinal (TCM) plants for systematic biological evaluation-rationale, methods and preliminary results from a Sino-american collaboration. Fitoterapia 82:17-33
51. Ekdahl CT, Kokaia Z, Lindvall O (2009) Brain inflammation and adult neurogenesis: the dual role ofmicroglia. Neuroscience 158:1021-1029
52. Eltzschig HK, Eckle T (2011) Ischemia and reperfusion-from mechanism to translation. Nat Med 17:1391-1401
53. Ernst E,Matrai A, Paulsen F (1987) Leukocyte rheology in recent stroke. Stroke 18:59-62 (Pubitemid 17016686)
54. Estrada C, Murillo-Carretero M (2005) Nitric oxide and adult neurogenesis in health and disease. Neuroscientist 11:294-307 (Pubitemid 41040859)
55. Fan T, Jiang WL, Zhu J, Zhang YF (2012) Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation. Biol Pharma Bull 35:2004-2009
56. Forstermann U (2010) Nitric oxide and oxidative stress in vascular disease. Pflugers Arch 459:923-939
57. Gao D, Zhang X, Jiang X, Peng Y, Huang W, Cheng G, Song L (2006) Resveratrol reduces the elevated level of MMP-9 induced by cerebral ischemia-reperfusion in mice. Life Sci 78:2564-2570
58. Gao L, Ji X, Song J, Liu P, Yan F, Gong W, Dang S, Luo Y (2009) Puerarin protects against ischemic brain injury in a rat model of transient focal ischemia. Neurol Res 31:402-406
59. Gao XQ, Yang CX, Chen GJ,Wang GY, Chen B, Tan SK, Liu JA, Yuan QL (2010) Ginsenoside Rb1 regulates the expressions of brain-derived neurotrophic factor and caspase-3 and induces neurogenesis in rats with experimental cerebral ischemia. J Ethnopharmacol 132:393-399
60. Garau A, Bertini R, Colotta F, Casilli F, Bigini P, Cagnotto A, Mennini T, Ghezzi P, Villa P (2005) Neuroprotection with the CXCL8 inhibitor repertaxin in transient brain ischemia. Cytokine 30:125-131
61. Gaur V, Aggarwal A, Kumar A (2009) Protective effect of naringin against ischemic reperfusion cerebral injury: possible neurobehavioral, biochemical and cellular alterations in rat brain. Eur J of pharm 616:147-154
62. Gelderblom M, Leypoldt F, Lewerenz J, Birkenmayer G, Orozco D, Ludewig P, Thundyil J, Arumugam TV, Gerloff C, Tolosa E, Maher P, Magnus T (2012) The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice. J Cereb Blood Flow Metab 32:835-843
63. Ghosh A, Sarkar S,Mandal AK, Das N (2013) Neuroprotective role of nanoencapsulated quercetin in combating ischemia-reperfusion induced neuronal damage in young and aged rats. PLoS One 8:e57735
64. Gidday JM, Gasche YG, Copin JC, Shah AR, Perez RS, Shapiro SD, Chan PH, Park TS (2005) Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am J Physiol-Heart C 289:H558-H568 (Pubitemid 41129369)
65. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918-934
66. Gobbel GT, Chan TY, Chan PH (1997) Nitric oxide- and superoxide-mediated toxicity in cerebral endothelial cells. J Pharmacol Exp Ther 282:1600-1607 (Pubitemid 27408346)
67. Gu Y, Dee CM, Shen J (2011) Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood-brain barrier permeability. Front Biosci (Schol Ed) 3:1216-1231
68. Gu Y, Zheng G, Xu M, Li Y, Chen X, Zhu W, Tong Y, Chung SK, Liu KJ, Shen J (2012) Caveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injury. J Neurochem 120:147-156
69. Guan T, Liu Q, Qian Y, Yang H, Kong J, Kou J, Yu B (2013) Ruscogenin reduces cerebral ischemic injury via NF-kappaB-mediated inflammatory pathway in the mouse model of experimental stroke. Eur J Pharma 714:303-311
70. Guegan C, Ceballos-Picot I, Chevalier E, Nicole A, Onteniente B, Sola B (1999) Reduction of ischemic damage in NGF-transgenic mice: correlation with enhancement of antioxidant enzyme activities. Neurobiol Dis 6:180-189 (Pubitemid 29297819)
71. Guo H, Hu LM, Wang SX, Wang YL, Shi F, Li H, Liu Y, Kang LY, Gao XM (2011) Neuroprotective effects of scutellarin against hypoxicischemic-induced cerebral injury via augmentation of antioxidant defense capacity. Chin J Physiol 54:399-405
72. Guo C, Tong L, Xi M, Yang H, Dong H, Wen A (2012) Neuroprotective effect of calycosin on cerebral ischemia and reperfusion injury in rats. J Ethnopharm 144:768-774
73. Gursoy-Ozdemir Y, Can A, Dalkara T (2004) Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia. Stroke 35:1449-1453 (Pubitemid 38697474)
74. Ha SK, Lee P, Park JA, Oh HR, Lee SY, Park J-H, Lee EH, Ryu JH, Lee KR, Kim SY (2008) Apigenin inhibits the production of NO and PGE2 in microglia and inhibits neuronal cell death in a middle cerebral artery occlusion-induced focal ischemia mice model. Neurochem Intern 52:878-886
75. Ha SK, Moon E, Ju MS, Kim DH, Ryu JH, Oh MS, Kim SY (2012) 6-Shogaol, a ginger product, modulates neuroinflammation: a new approach to neuroprotection. Neuropharmacology 63:211-223
76. Hanisch UK, Kettenmann H (2007)Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387-1394
77. Hara H, Huang PL, Panahian N, Fishman MC, Moskowitz MA (1996) Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion. J Cereb Blood Flow Metab 16:605-611 (Pubitemid 26227069)
78. Hayakawa K, Qiu J, Lo EH (2010) Biphasic actions of HMGB1 signaling in inflammation and recovery after stroke. Ann N YAcad Sci 1207:50-57
79. Hazra S, Hossain M, Suresh Kumar G (2013) Binding of isoquinoline alkaloids berberine, palmatine and coralyne to hemoglobin: structural and thermodynamic characterization studies. Mol Biosyst 9:143-153
80. Hei M, Luo Y, Zhang X, Liu F (2011) Tanshinone IIa alleviates the biochemical changes associated with hypoxic ischemic brain damage in a rat model. Phytother Res 25:1865-1869
81. HenrichNoack P, Prehn JHM, Krieglstein J (1996) TGF-beta 1 protects hippocampal neurons against degeneration caused by transient global ischemia - dose-response relationship and potential neuroprotective mechanisms. Stroke 27:1609-1614
82. Heo JH, Han SW, Lee SK (2005) Free radicals as triggers of brain edema formation after stroke. Free Radic Biol Med 39:51-70
83. Herrmann O, Tarabin V, Suzuki S, Attigah N, Coserea I, Schneider A, Vogel J, Prinz S, Schwab S, Monyer H (2003) Regulation of body temperature and neuroprotection by endogenous interleukin-6 in cerebral ischemia. J Cereb Blood Flow Metab 23:406-415 (Pubitemid 36403022)
84. Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, Blom B, Homola ME, Streit WJ, Brown MH, Barclay AN, Sedgwick JD (2000) Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290:1768-1771 (Pubitemid 32004808)
85. Hong JS, Chu YK, Lee H, Ahn BH, Park JH, Kim MJ, Lee S, Ryoo HS, Jang JH, Lee SR, Park JW (2012) Effects of berberine on hippocampal neuronal damage and matrix metalloproteinase-9 activity following transient global cerebral ischemia. J Neurosci Res 90:489-497
86. Hou SZ, Li Y, Zhu XL, Wang ZY, Wang X, Xu Y (2012) Ameliorative effects of diammonium glycyrrhizinate on inflammation in focal cerebral ischemic-reperfusion injury. Brain Res 1447:20-27
87. Hsieh C-L, Cheng C-Y, Tsai T-H, I-h L, Liu C-H, Chiang S-Y, Lin J-G, Lao C-J, Tang N-Y (2006) Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemia-reperfusion injured rats. J Ethnopharmacol 106:208-215 (Pubitemid 43766198)
88. Hu H, Zhu LJ, Huang ZS, Ji QS, Chatterjee M, Zhang W, Li NL (2010) Platelets enhance lymphocyte adhesion and infiltration into arterial thrombus. Thromb Haemost 104:1184-1192
89. Hu YY, Huang M, Dong XQ, Xu QP, Yu WH, Zhang ZY (2011) Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain: possible involvement of toll-like receptor 4/nuclear factorkappa B pathway. J Ethnopharmacol 137:1462-1468
90. Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677-736 (Pubitemid 32695243)
91. Huang J, Kim LJ, Mealey R, Marsh HC, Zhang Y, Tenner AJ, Connolly ES, Pinsky DJ (1999) Neuronal protection in stroke by an sLe(x)-glycosylated complement inhibitory protein. Science 285:595-599
92. Huang J, Upadhyay UA, Tamargo RJ (2006) Inflammation in stroke and focal cerebral ischemia. Surg Neurol 66:232-245 (Pubitemid 44279808)
93. Hughes PM, Allegrini PR, Rudin M, Perry VH, Mir AK, Wiessner C (2002) Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. J Cereb Blood Flow Metab 22:308-317 (Pubitemid 34203058)
94. Iadecola C, Anrather J (2011) The immunology of stroke: from mechanisms to translation. Nat Med 17:796-808
95. Ikeda-Matsuo Y (2013) The role of prostaglandin e2 in stroke-reperfusion injury. Yakugaku Zasshi 133:947-954
96. Inacio AR, Ruscher K, Leng L, Bucala R, Deierborg T (2011) Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke. J Cereb Blood Flow Metab 31:1093-1106
97. Innamorato NG, Rojo AI, García-Yagüe ÁJ, Yamamoto M, de Ceballos ML, Cuadrado A (2008) The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol 181:680-689
98. Javadov S, Kuznetsov A (2013) Mitochondrial permeability transition and cell death: the role of cyclophilin d. Front Physiol 4:76
99. Jefferson A, Ruparelia N, Choudhury RP (2013) Exogenous microparticles of iron oxide bind to activated endothelial cells but, unlikemonocytes, do not trigger an endothelial response. Theranostics 3:428-436
100. Ji H, Zhang X, Du Y, Liu H, Li S, Li L (2012) Polydatin modulates inflammation by decreasing NF-kappaB activation and oxidative stress by increasing Gli1, Ptch1, SOD1 expression and ameliorates blood-brain barrier permeability for its neuroprotective effect in pMCAO rat brain. Brain Res Bull 87:50-59
101. Jian Liu K, Rosenberg GA (2005) Matrix metalloproteinases and free radicals in cerebral ischemia. Free Radic Biol Med 39:71-80
102. Jiang F, Zhang Y, Dusting GJ (2011a) NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol Rev 63:218-242
103. Jiang M, Wang XY, Zhou WY, Li J, Wang J, Guo LP (2011b) Cerebral protection of salvianolic acid a by the inhibition of granulocyte adherence. Am J Chin Med 39:111-120
104. Jin K, Mao XO, Sun Y, Xie L, Jin L, Nishi E, Klagsbrun M, Greenberg DA (2002) Heparin-binding epidermal growth factor-like growth factor: hypoxia-inducible expression in vitro and stimulation of neurogenesis in vitro and in vivo. J Neurosci 22:5365-5373 (Pubitemid 35386458)
105. Jin R,Yang G, Li G (2010) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87:779-789
106. Johnston SC, Mendis S, Mathers CD (2009a) Global variation in stroke burden and mortality. Stroke 40:E142-E142
107. Johnston SC, Mendis S, Mathers CD (2009b) Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol 8:345-354
108. Kamel H, Iadecola C (2012) Brain-immune interactions and ischemic stroke: clinical implications. Arch Neurol 69:576-581
109. Kao TK, Chang CY, Ou YC, Chen WY, Kuan YH, Pan HC, Liao SL, Li GZ, Chen CJ (2013) Tetramethylpyrazine reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. Exp Neurol 247:188-201
110. Kilic U, Kilic E, Dietz GPH, Bahr M (2003) Intravenous TAT-GDNF is protective after focal cerebral ischemia in mice. Stroke 34:1304-1310 (Pubitemid 36547533)
111. Kim JB, Sig Choi J, Yu YM, Nam K, Piao CS, Kim SW, Lee MH, Han PL, Park JS, Lee JK(2006) HMGB1, a novel cytokine-likemediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci 26:6413-6421 (Pubitemid 44318322)
112. Kono H, Rock KL (2008) How dying cells alert the immune system to danger. Nat Rev Immunol 8:279-289 (Pubitemid 351432799)
113. Konoeda F, Shichita T, Yoshida H, Sugiyama Y, Muto G, Hasegawa E, Morita R, Suzuki N, Yoshimura A (2010) Therapeutic effect of IL-12/23 and their signaling pathway blockade on brain ischemia model. Biochem Bioph Res Co 402:500-506
114. Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 7:97
115. Lalancette-Hebert M, Gowing G, Simard A, Weng YC, Kriz J (2007) Selective ablation of proliferatingmicroglial cells exacerbates ischemic injury in the brain. J Neurosci 27:2596-2605 (Pubitemid 46393607)
116. Lambertsen KL, Gregersen R, Finsen B (2002) Microglial-macrophage synthesis of tumor necrosis factor after focal cerebral ischemia in mice is strain dependent. J Cereb Blood Flow Metab 22:785-797 (Pubitemid 34747596)
117. Lambertsen KL, Meldgaard M, Ladeby R, Finsen B (2005) A quantitative study of microglial-macrophage synthesis of tumor necrosis factor during acute and late focal cerebral ischemia in mice. J Cereb Blood Flow Metab 25:119-135 (Pubitemid 40096903)
118. Lambertsen KL, Clausen BH, Babcock AA, Gregersen R, Fenger C, Nielsen HH, Haugaard LS, Wirenfeldt M, Nielsen M, Dagnaes-Hansen F, Bluethmann H, Faergeman NJ, Meldgaard M, Deierborg T, Finsen B (2009) Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. J Neurosci 29:1319-1330
119. Lambertsen KL, Biber K, Finsen B (2012) Inflammatory cytokines in experimental and human stroke. J Cereb Blood Flow Metab 32:1677-1698
120. Lawrence MB, Springer TA (1991) Leukocytes roll on a selectin at physiological flow-rates - distinction from and prerequisite for adhesion through integrins. Cell 65:859-873 (Pubitemid 121001317)
121. Lee E, Chen H-Y, Lee M-Y, Chen T-Y, Hsu Y-S, Hu Y-L, Chang G-L,Wu T-S (2005a) Cinnamophilin reduces oxidative damage and protects against transient focal cerebral ischemia in mice. Free Rad Biol Med 39:495-510 (Pubitemid 41021648)
122. Lee ST, Chu K, Jung KH, Ko SY, Kim EH, Sinn DI, Lee YS, Lo EH, Kim M, Roh JK (2005b) Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res 1058:120-128 (Pubitemid 41416806)
123. Lee EJ, Chen HY, Hung YC, Chen TY, Lee MY, Yu SC, Chen YH, Chuang IC, Wu TS (2009) Therapeutic window for cinnamophilin following oxygen-glucose deprivation and transient focal cerebral ischemia. Exp Neurol 217:74-83
124. Lee JK, Kwak HJ, Piao MS, Jang JW, Kim SH, Kim HS (2011) Quercetin reduces the elevated matrixmetalloproteinases-9 level and improves functional outcome after cerebral focal ischemia in rats. Acta Neurochir (Wien) 153:1321-1329, discussion 1329
125. Lee TH, Jung CH, Lee DH (2012) Neuroprotective effects of schisandrin B against transient focal cerebral ischemia in sprague-dawley rats. Food and Chem Toxic 50:4239-4245
126. Li Q, Han LP, Li ZH, Zhang JT, Tang MK (2010) Salvianolic acid B alleviate the disruption of blood-brain barrier in rats after cerebral ischemia-reperfusion by inhibiting MAPK pathway. Yao Xue Xue Bao 45:1485-1490
127. Li M, Qu YZ, Zhao ZW, Wu SX, Liu YY, Wei XY, Gao L, Gao GD (2012a) Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules. Neurochem Int 60:458-465
128. Li XL, Hu YJ, Wang H, Yu BQ, Yue HL (2012b) Molecular spectroscopy evidence of berberine binding to DNA: comparative binding and thermodynamic profile of intercalation. Biomacromolecules 13:873-880
129. Li Y, Zhuang P, Shen B, Zhang Y, Shen J (2012c) Baicalin promotes neuronal differentiation of neural stem/progenitor cells through modulating p-stat3 and bHLH family protein expression. Brain Res 1429:36-42
130. Li Z, Pang L, Fang F, Zhang G, Zhang J, Xie M, Wang L (2012d) Resveratrol attenuates brain damage in a rat model of focal cerebral ischemia via up-regulation of hippocampal Bcl-2. Brain Res 1450:116-124
131. Li M, Ma RN, Li LH, Qu YZ, Gao GD (2013) Astragaloside IV reduces cerebral edema post-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4. Eur J Pharmacol 715:189-195
132. Liesz A, Suri-Payer E, Veltkamp C, Doerr H, Sommer C, Rivest S, Giese T, Veltkamp R (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15:192-199
133. Lim DW, Lee C, Kim IH, Kim YT (2013) Anti-inflammatory effects of total isoflavones from pueraria lobata on cerebral ischemia in rats. Molecules 18:10404-10412
134. Lin Y, Zhang JC, Fu J, Chen F, Wang J, Wu ZL, Yuan SY (2013) Hyperforin attenuates brain damage induced by transient middle cerebral, artery occlusion (MCAO) in rats via inhibition of TRPC6 channels degradation. J Cereb Blood Flow Metab 33:253-262
135. Lindsberg PJ, Strbian D, Karjalainen-Lindsberg ML (2010) Mast cells as early responders in the regulation of acute blood-brain barrier changes after cerebral ischemia and hemorrhage. J Cereb Blood Flow Metab 30:689-702
136. Liou KT, Shen YC, Chen CF, Tsao CM, Tsai SK (2003) Honokiol protects rat brain from focal cerebral ischemia-reperfusion injury by inhibiting neutrophil infiltration and reactive oxygen species production. Brain Res 992:159-166
137. Liu K, Mori S, Takahashi HK, Tomono Y, Wake H, Kanke T, Sato Y, Hiraga N, Adachi N, Yoshino T, Nishibori M (2007) Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats. FASEB J 21:3904-3916 (Pubitemid 350232348)
138. Liu X, Xia J, Wang L, Song Y, Yang J, Yan Y, Ren H, Zhao G (2009) Efficacy and safety of ginsenoside-Rd for acute ischaemic stroke: a randomized, double-blind, placebo-controlled, phase II multicenter trial. Eur J Neurol 16:569-575
139. Liu ZJ, Liu W, Liu L, Xiao C, Wang Y, Jiao JS (2013) Curcumin protects neuron against cerebral ischemia-induced inflammation through improving PPAR-gamma function. Evid Based Complement Alternat Med 2013:470975
140. Lo EH (2010) Degeneration and repair in central nervous system disease. Nat Med 16:1205-1209
141. Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399-415 (Pubitemid 37280178)
142. Loh KP, Qi J, Tan BK, Liu XH, Wei BG, Zhu YZ (2010) Leonurine protects middle cerebral artery occluded rats through antioxidant effect and regulation of mitochondrial function. Stroke 41:2661-2668
143. Lopez-ArmadaMJ, Riveiro-Naveira RR, Vaamonde-Garcia C, Valcarcel-Ares MN (2013) Mitochondrial dysfunction and the inflammatory response. Mitochondrion 13:106-118
144. Lopez-Sanchez C, Martin-Romero FJ, Sun F, Luis L, Samhan-Arias AK, Garcia-Martinez V, Gutierrez-Merino C (2007) Blood micromolar concentrations of kaempferol afford protection against ischemia/reperfusion-induced damage in rat brain. Brain Res 1182:123-137 (Pubitemid 350086989)
145. Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB): nuclear weapon in the immune arsenal. Nat Rev Immunol 5:331-342 (Pubitemid 40516158)
146. Luheshi NM, Kovacs KJ, Lopez-Castejon G, Brough D, Denes A (2011) Interleukin-1alpha expression precedes IL-1beta after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues. J Neuroinflammation 8:186
147. Ma Y, Sullivan JC, Schreihofer DA (2010) Dietary genistein and equol (4′, 7 isoflavandiol) reduce oxidative stress and protect rats against focal cerebral ischemia. Am J Physiol Regul Integr Comp Physiol 299:R871-R877
148. Majumder P, Trujillo CA, Lopes CG, Resende RR, Gomes KN, Yuahasi KK, Britto LRG, Ulrich H (2007) New insights into purinergic receptor signaling in neuronal differentiation, neuroprotection, and brain disorders. Purinerg Signal 3:317-331
149. Mander P, Borutaite V, Moncada S, Brown GC (2005) Nitric oxide from inflammatory-activated glia synergizes with hypoxia to induce neuronal death. J Neurosci Res 79:208-215 (Pubitemid 40116437)
150. Matsumoto H, Kumon Y, Watanabe H, Ohnishi T, Takahashi H, Imai Y, Tanaka J (2007) Expression of CD200 by macrophage-like cells in ischemic core of rat brain after transient middle cerebral artery occlusion. Neurosci Lett 418:44-48 (Pubitemid 46602702)
151. Mattila OS, Strbian D, Saksi J, Pikkarainen TO, Rantanen V, Tatlisumak T, Lindsberg PJ (2011) Cerebral mast cells mediate blood-brain barrier disruption in acute experimental ischemic stroke through perivascular gelatinase activation. Stroke 42:3600-U3410
152. McCoy MK, Tansey MG (2008) TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J Neuroinflammation 5:45
153. Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M (2012) IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond) 122:143-159
154. Mildner A, Schlevogt B, Kierdorf K, Bottcher C, Erny D, Kummer MP, Quinn
155. Moskowitz MA, Lo EH, Iadecola C (2010) The science of stroke: mechanisms in search of treatments. Neuron 67:181-198
156. Moussaieff A, Yu J, Zhu H, Gattoni-Celli S, Shohami E, Kindy MS (2012) Protective effects of incensole acetate on cerebral ischemic injury. Brain Res 1443:89-97
157. Muhammad S, Barakat W, Stoyanov S, Murikinati S, Yang H, Tracey KJ, Bendszus M, Rossetti G, Nawroth PP, Bierhaus A, Schwaninger M (2008) The HMGB1 receptor RAGE mediates ischemic brain damage. J Neurosci 28:12023-12031
158. Muralikrishna Adibhatla R, Hatcher JF (2006) Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radical Biol Med 40:376-387
159. Murphy S, Gibson CL (2007) Nitric oxide, ischaemia and brain inflammation. Biochem Soc Trans 35:1133-1137 (Pubitemid 350206445)
160. Murray KN, Buggey HF, Denes A, Allan SM (2013) Systemic immune activation shapes stroke outcome. Mol Cell Neurosci 53:14-25
161. Nieman DC, Laupheimer MW, Ranchordas MK, Burke LM, Stear SJ, Castell LM (2012) A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance-part 33. Br J Sports Med 46:618-620
162. O'Garra A, Vieira P (2004) Regulatory T cells and mechanisms of immune system control. Nat Med 10:801-805 (Pubitemid 39070850)
163. Okada Y, Copeland BR, Mori E, Tung MM, Thomas WS, Delzoppo GJ (1994) P-selectin and intercellular-adhesion molecule-1 expression after focal brain ischemia and reperfusion. Stroke 25:202-211
164. Okada Y, Copeland BR, Hamann GF, Koziol JA, Cheresh DA, delZoppo GJ (1996) Integrin alpha(v)beta(3) is expressed in selected microvessels after focal cerebral ischemia. Am J Pathol 149:37-44 (Pubitemid 26230976)
165. Oyama Y, Fuchs PA, Katayama N, Noda K (1994) Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca2+-loaded brain neurons. Brain Res 635:125-129 (Pubitemid 24031396)
166. Pal G, Vincze C, Renner E, Wappler EA, Nagy Z, Lovas G, Dobolyi A (2012) Time course, distribution and cell types of induction of transforming growth factor betas following middle cerebral artery occlusion in the rat brain. PLoS One 7:e46731
167. Pan J, Konstas AA, Bateman B, Ortolano GA, Pile-Spellman J (2007) Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology 49:93-102 (Pubitemid 46218581)
168. Park EM, Cho S, Frys KA, Glickstein SB, Zhou P, Anrather J, Ross ME, Iadecola C (2006) Inducible nitric oxide synthase contributes to gender differences in ischemic brain injury. J Cereb Blood Flow Metab 26:392-401
169. Park JW, Jang YH, Kim JM, Lee H, Park WK, Lim MB, Chu YK, Lo EH, Lee SR (2009) Green tea polyphenol (-)-epigallocatechin gallate reduces neuronal cell damage and up-regulation of MMP-9 activity in hippocampal CA1 and CA2 areas following transient global cerebral ischemia. J Neurosci Res 87:567-575
170. Patenaude A, Murthy MR, Mirault ME (2005) Emerging roles of thioredoxin cycle enzymes in the central nervous system. Cell Mol Life Sci 62:1063-1080 (Pubitemid 40868526)
171. Petry KG, Boiziau C, Dousset V, Brochet B (2007) Magnetic resonance imaging of human brain macrophage infiltration. Neurotherapeutics 4:434-442 (Pubitemid 46962415)
172. Piao HZ, Jin SA, Chun HS, Lee JC, Kim WK (2004) Neuroprotective effect of wogonin: potential roles of inflammatory cytokines. Arch Pharm Res 27:930-936
173. Pisetsky DS (2013) The Translocation of Nuclear Molecules During Inflammation and Cell Death. Antioxid Redox Signal 00:1-9
174. Qi J, Hong ZY, Xin H, Zhu YZ (2010) Neuroprotective effects of leonurine on ischemia/reperfusion-induced mitochondrial dysfunctions in rat cerebral cortex. Biol Pharm Bull 33:1958-1964
175. Qian L, Xu Z, Zhang W, Wilson B, Hong J-S, Flood PM (2007) Sinomenine, a natural dextrorotatory morphinan analog, is anti-inflammatory and neuroprotective through inhibition of microglial NADPH oxidase. J Neuroinflamm 4:23
176. Raoof M, Zhang Q, Itagaki K, Hauser CJ (2010) Mitochondrial peptides are potent immune activators that activate human neutrophils via FPR-1. J Trauma 68:1328-1332, discussion 1332-1324
177. Rashidian J, Rousseaux MW, Venderova K, Qu D, Callaghan SM, Phillips M, Bland RJ, During MJ, Mao Z, Slack RS, Park DS (2009) Essential role of cytoplasmic cdk5 and Prx2 in multiple ischemic injury models, in vivo. J Neurosci 29:12497-12505
178. Raza SS, Khan MM, Ashafaq M, Ahmad A, Khuwaja G, Khan A, Siddiqui MS, Safhi MM, Islam F (2011) Silymarin protects neurons from oxidative stress associated damages in focal cerebral ischemia: a behavioral, biochemical and immunohistological study in wistar rats. J Neurol Sci 309:45-54
179. Rink C, Khanna S (2011) Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke. Antioxid Redox Signal 14:1889-1903
180. Saadane A, Masters S, DiDonato J, Li J, Berger M (2007) Parthenolide inhibits IκB kinase, NF-κB activation, and inflammatory response in cystic fibrosis cells and mice. Am J Respir Cell Mol Biol 36:728
181. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137:47-59
182. Sakai M, Zhang M, Homma T, Garrick B, Abraham JA, McKanna JA, Harris RC (1997) Production of heparin binding epidermal growth factor-like growth factor in the early phase of regeneration after acute renal injury. Isolation and localization of bioactive molecules. J Clin Invest 99:2128-2138 (Pubitemid 27203769)
183. Schabitz WR, Hoffmann TT, Heiland S, Kollmar R, Bardutzky J, Sommer C, Schwab S (2001) Delayed neuroprotective effect of insulin-like growth factor-I after experimental transient focal cerebral ischemia monitored with MRI. Stroke 32:1226-1233 (Pubitemid 32825815)
184. Schilling M, Besselmann M, Leonhard C, Mueller M, Ringelstein EB, Kiefer R (2003) Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia: a study in green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol 183:25-33 (Pubitemid 37075853)
185. Schilling M, Besselmann M, Muller M, Strecker JK, Ringelstein EB, Kiefer R (2005) Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia: an investigation using green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol 196:290-297 (Pubitemid 41607817)
186. Schneider A, Kruger C, Steigleder T, Weber D, Pitzer C, Laage R, Aronowski J, Maurer MH, Gassler N, Mier W, Hasselblatt M, Kollmar R, Schwab S, Sommer C, Bach A, Kuhn HG, Schabitz WR (2005) The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest 115:2083-2098 (Pubitemid 41134150)
187. Schock SC, Munyao N, Yakubchyk Y, Sabourin LA, Hakim AM, Ventureyra ECG, Thompson CS (2007) Cortical spreading depression releases ATP into the extracellular space and purinergic receptor activation contributes to the induction of ischemic tolerance. Brain Res 1168:129-138 (Pubitemid 47320630)
188. Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821-832
189. Schweitzer PJ, Fallon BA,Mann JJ, Kumar JS (2010) PET tracers for the peripheral benzodiazepine receptor and uses thereof. Drug Discov Today 15:933-942
190. Sevimli S, Diederich K, Strecker JK, Schilling M, Klocke R, Nikol S, Kirsch F, Schneider A, Schabitz WR (2009) Endogenous brain protection by granulocyte-colony stimulating factor after ischemic stroke. Exp Neurol 217:328-335
191. Shen L, Zhang J (2007) NMDA receptor and iNOS are involved in the effects of ginsenoside Rg1 on hippocampal neurogenesis in ischemic gerbils. Neurol Res 29:270-273 (Pubitemid 46802364)
192. Shen JG, Ma S, Chan PS, Lee W, Fung PCW, Cheung RTF, Tong Y, Liu KJ (2006) Nitric oxide down-regulates caveolin-1 expression in rat brains during focal cerebral ischemia and reperfusion injury. J Neurochem 96:1078-1089
193. Shichita T, Sugiyama Y, Ooboshi H, Sugimori H, Nakagawa R, Takada I, Iwaki T, Okada Y, Iida M, Cua DJ, Iwakura Y, Yoshimura A (2009) Pivotal role of cerebral interleukin-17-producing gamma delta T cells in the delayed phase of ischemic brain injury. Nat Med 15: 946-U150
194. Shichita T, Ago T, Kamouchi M, Kitazono T, Yoshimura A, Ooboshi H (2012a) Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke. J Neurochem 123(Suppl 2):29-38
195. Shichita T, Hasegawa E, Kimura A, Morita R, Sakaguchi R, Takada I, Sekiya T, Ooboshi H, Kitazono T, Yanagawa T, Ishii T, Takahashi H, Mori S, Nishibori M, Kuroda K, Akira S, Miyake K, Yoshimura A (2012b) Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain. Nat Med 18:911-917
196. Shin YM, Jung HJ, Choi WY, Lim CJ (2013) Antioxidative, anti-inflammatory, and matrix metalloproteinase inhibitory activities of 20(S)-ginsenoside Rg3 in cultured mammalian cell lines. Mol Biol Rep 40:269-279
197. Simi A, Tsakiri N,Wang P, Rothwell N (2007) Interleukin-1 and inflammatory neurodegeneration. Biochem Soc Trans 35:1122-1126 (Pubitemid 350206443)
198. Sobel RA, Mitchell ME, Fondren G (1990) Intercellular-adhesion molecule-1 (icam-1) in cellular immune-reactions in the human central-nervous-system. Am J Pathol 136:1309-1316 (Pubitemid 20210330)
199. Soriano SG, Amaravadi LS, Wang YF, Zhou H, Yu GX, Tonra JR, Fairchild-Huntress V, Fang Q, Dunmore JH, Huszar D, Pan Y (2002) Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury. J Neuroimm 125:59-65 (Pubitemid 34327454)
200. Stanimirovic D, Shapiro A, Wong J, Hutchison J, Durkin J (1997) The induction of ICAM-1 in human cerebromicrovascular endothelial cells (HCEC) by ischemia-like conditions promotes enhanced neutrophil/HCEC adhesion. J Neuroimm 76:193-205 (Pubitemid 27272647)
201. Strbian D, Karjalainen-Lindsberg ML, Tatlisumak T, Lindsberg PJ (2006) Cerebral mast cells regulate early ischemic brain swelling and neutrophil accumulation. J Cereb Blood Flow Meteb 26:605-612
202. Suchadolskiene O, Pranskunas A, Baliutyte G, Veikutis V, Dambrauskas Z, Vaitkaitis D, Borutaite V (2014) Microcirculatory, mitochondrial, and histological changes following cerebral ischemia in swine. BMC Neurosci 15:2
203. Sun YJ, Jin KL, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA (2003) VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 111:1843-1851 (Pubitemid 38057729)
204. Sun Y, Yu P, Zhang G, Wang L, Zhong H, Zhai Z, Wang Y (2012) Therapeutic effects of tetramethylpyrazine nitrone in rat ischemic stroke models. J Neurosci Res 90:1662-1669
205. Sun S, Sursal T, Adibnia Y, Zhao C, Zheng Y, Li H, Otterbein LE, Hauser CJ, Itagaki K (2013) Mitochondrial DAMPs increase endothelial permeability through neutrophil dependent and independent pathways. PLoS One 8:e59989
206. Suofu Y, Clark J, Broderick J,Wagner KR, Tomsick T, Sa Y, Lu A (2010) Peroxynitrite decomposition catalyst prevents matrix metalloproteinase activation and neurovascular injury after prolonged cerebral ischemia in rats. J Neurochem 115:1266-1276
207. Sutherland BA, Shaw OM, Clarkson AN, Jackson DN, Sammut IA, Appleton I (2005) Neuroprotective effects of (-)-epigallocatechin gallate following hypoxia-ischemia-induced brain damage: novel mechanisms of action. FASEB J 19:258-260 (Pubitemid 40189274)
208. Swanson RA, Ying W, Kauppinen TM (2004) Astrocyte influences on ischemic neuronal death. Curr Mol Med 4:193-205 (Pubitemid 38425914)
209. Syapin P (2008) Regulation of haeme oxygenase-1 for treatment of neuroinflammation and brain disorders. Br J Pharm 155:623-640
210. Szabo C, Ischiropoulos H, Radi R (2007) Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev Drug Discov 6:662-680 (Pubitemid 47207751)
211. Tang C, Xue H, Bai C, Fu R,Wu A (2010) The effects of tanshinone IIA on blood-brain barrier and brain edema after transient middle cerebral artery occlusion in rats. Phytomedicine 17:1145-1149
212. Tang SC, Wang YC, Li YI, Lin HC, Manzanero S, Hsieh YH, Phipps S, Hu CJ, Chiou HY, Huang YS, Yang WS, Mattson MP, Arumugam TV, Jeng JS (2013) Functional role of soluble receptor for advanced glycation end products in stroke. Arterioscl Throm Vas 33:585-594
213. Thippeswamy BS, Nagakannan P, Shivasharan BD, Mahendran S, Veerapur VP, Badami S (2011) Protective effect of embelin from embelia ribes burm. Against transient global ischemia-induced brain damage in rats. Neurotox Res 20:379-386
214. Thiyagarajan M, Kaul CL, Sharma SS (2004) Neuroprotective efficacy and therapeutic time window of peroxynitrite decomposition catalysts in focal cerebral ischemia in rats. Br J Pharmacol 142:899-911 (Pubitemid 38998103)
215. Tian J, Fu F, Geng M, Jiang Y, Yang J, Jiang W, Wang C, Liu K (2005) Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci Lett 374:92-97 (Pubitemid 40092203)
216. Tian J, Zhang S, Li G, Liu Z, Xu B (2009) 20(S)-ginsenoside Rg3, a neuroprotective agent, inhibitsmitochondrial permeability transition pores in rat brain. Phytother Res 23:486-491
217. Tsai SK, Hung LM, Fu YT, Cheng H, Nien MW, Liu HY, Zhang FB, Huang SS (2007) Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats. J Vasc Surg 46:346-353 (Pubitemid 47102097)
218. Tsung-Kuei Kao C-YC, Yen-Chuan O, Chen W-Y, Kuan Y-H (2013) Tetramethylpyrazine reduces cellular inflammatory response following permanent focal cerebral ischemia in rats. Exp Neurology 247:188-201
219. Vaamonde-Garcia C, Riveiro-Naveira RR, Valcarcel-Ares MN, Hermida-Carballo L, Blanco FJ, Lopez-Armada MJ (2012) Mitochondrial dysfunction increases inflammatory responsiveness to cytokines in normal human chondrocytes. Arthritis Rheum 64:2927-2936
220. Vakili A, Einali MR, Bandegi AR (2012) Protective effect of crocin against cerebral ischemia in a dose-dependent manner in a Rat model of ischemic stroke. J Stroke Cerebrovasc Dis 23:106-113
221. Vila N, Castillo J, Dávalos A, Chamorro Á (2000) Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 31:2325-2329
222. Vonandrian UH, Chambers JD, Mcevoy LM, Bargatze RF, Arfors KE, Butcher EC (1991) 2-Step model of leukocyte endothelial-cell interaction in inflammation - distinct roles for lecam-1 and the leukocyte beta-2 integrins invivo. Proc Natl Acad Sci U S A 88:7538-7542 (Pubitemid 21915188)
223. Wang ZF, Wang J, Zhang HY, Tang XC (2008) Huperzine a exhibits anti?inflammatory and neuroprotective effects in a rat model of transient focal cerebral ischemia. J Neurochem 106:1594-1603
224. Wang T, Gu J, Wu PF, Wang F, Xiong Z, Yang YJ, Wu WN, Dong LD, Chen JG (2009) Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-kappaB pathways and inhibition of intracellular ROS/RNS generation. Free Radic Biol Med 47:229-240
225. Wang H-Q, Sun X-B, Xu Y-X, Zhao H, Zhu Q-Y, Zhu C-Q (2010a) Astaxanthin upregulates heme oxygenase-1 expression through ERK1/2 pathway and its protective effect against beta-amyloid-induced cytotoxicity in SH-SY5Y cells. Brain Res 1360:159-167
226. Wang W, Xu J, Li L, Wang P, Ji X, Ai H, Zhang L, Li L (2010b) Neuroprotective effect of morroniside on focal cerebral ischemia in rats. Brain Res Bull 83:196-201
227. Wang T, Jiang N, Han B, Liu W, Liu T, Fu F, Zhao D (2011) Escin attenuates cerebral edema induced by acute omethoate poisoning. Toxicol Mech Methods 21:400-405
228. Wang C, Pei A, Chen J, Yu H, Sun ML, Liu CF, Xu X (2012) A natural coumarin derivative esculetin offers neuroprotection on cerebral ischemia/reperfusion injury in mice. J Neurochem 121:1007-1013
229. Wang Y, Ge P, Zhu Y (2013) TLR2 and TLR4 in the brain injury caused by cerebral ischemia and reperfusion.Mediat Inflamm 2013:124614
230. Watanabe T, Okuda Y, Nonoguchi N, Zhao MZ, Kajimoto Y, Furutama D, Yukawa H, Shibata MA, Otsuki Y, Kuroiwa T, Miyatake S (2004) Postischemic intraventricular administration of FGF-2 expressing adenoviral vectors improves neurologic outcome and reduces infarct volume after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab 24:1205-1213 (Pubitemid 39482481)
231. Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandercock P, Wardlaw J, Dennis M, Sudlow C (2009) Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. PLoS Med 6:e1000145
232. Wu WN, Wu PF, Chen XL, Zhang Z, Gu J, Yang YJ, Xiong QJ, Ni L, Wang F, Chen JG (2011) Sinomenine protects against ischaemic brain injury: involvement of co-inhibition of acid-sensing ion channel 1a and L-type calciumchannels. Br J Pharmacol 164:1445-1459
233. Wynn TA, Chawla A, Pollard JW (2013) Macrophage biology in development, homeostasis and disease. Nature 496:445-455
234. Xing C, Arai K, Lo EH, Hommel M (2012) Pathophysiologic cascades in ischemic stroke. Int J Stroke 7:378-385
235. Xiong XX, Gu LJ, Zhang HF, Xu BH, Zhu SM, Zhao H (2013) The protective effects of T cell deficiency against brain injury are ischemic model-dependent in rats. Neurochem Intern 62:265-270
236. Xu M, Chen X, Gu Y, Peng T, Yang D, Chang RC, So KF, Liu K, Shen J (2013) Baicalin can scavenge peroxynitrite and ameliorate endogenous peroxynitrite-mediated neurotoxicity in cerebral ischemiare-perfusion injury. J Ethnopharmacol 150:116-124
237. Yanai H, Ban T, Wang ZC, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, Savitsky D, Ronfani L, Akira S, Bianchi ME, Honda K, Tamura T, Kodama T, Taniguchi T (2009) HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 462:99-U110
238. Yang Y, Estrada EY, Thompson JF, Liu W, Rosenberg GA (2007) 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 27:697-709 (Pubitemid 46474608)
239. Yao R-Q, Zhang L, Wang W, Li L (2009) Cornel iridoid glycoside promotes neurogenesis and angiogenesis and improves neurological function after focal cerebral ischemia in rats. Brain Res Bull 79:69-76
240. Ye R, Yang Q, Kong X, Han J, Zhang X, Zhang Y, Li P, Liu J, Shi M, Xiong L, Zhao G (2011a) Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats. Neurochem Int 58:391-398
241. Ye RD, Kong XW, Yang QZ, Zhang YX, Han JL, Zhao G (2011b) Ginsenoside Rd attenuates redox imbalance and improves stroke outcome after focal cerebral ischemia in aged mice. Neuropharmacology 61:815-824
242. Yilmaz G, Arumugam TV, Stokes KY, Granger DN (2006) Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 113:2105-2112
243. Yuan QL, Yang CX, Xu P, Gao XQ, Deng L, Chen P, Sun ZL, Chen QY (2007) Neuroprotective effects of ginsenoside Rb1 on transient cerebral ischemia in rats. Brain Res 1167:1-12 (Pubitemid 47302431)
244. Zhang B, Hata R, Zhu P, Sato K,Wen T-C, Yang L, Fujita H,Mitsuda N, Tanaka J, Samukawa K (2005) Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb1, that upregulates Bcl-xL expression. J Cereb Blood Flow Metab 26:708-721
245. Zhang LM, Fu FH, Zhang XM, Zhu M, Wang TA, Fan HY (2010a) Escin attenuates cognitive deficits and hippocampal injury after transient global cerebral ischemia in mice via regulating certain inflammatory genes. Neurochem Intern 57:119-127
246. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ (2010b) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104- 107
247. Zhang J, Takahashi HK, Liu K, Wake H, Liu R, Maruo T, Date I, Yoshino T, Ohtsuka A, Mori S, Nishibori M (2011) Anti-high mobility group box-1 monoclonal antibody protects the blood-brain barrier from ischemia-induced disruption in rats. Stroke 42: 1420-1428
248. Zhang Q, Qian Z, Pan L, Li H, Zhu H (2012) Hypoxia-inducible factor 1 mediates the anti-apoptosis of berberine in neurons during hypoxia/ischemia. Acta Physiol Hung 99:311-323
249. Zhang L, Zhao H, Zhang X, Chen L, Zhao X, Bai X, Zhang J (2013a) Nobiletin protects against cerebral ischemia via activating the p-Akt, p-CREB, BDNF and Bcl-2 pathway and ameliorating BBB permeability in rat. Brain Res Bull 96:45-53
250. Zhang P, Liu X, Zhu Y, Chen S, Zhou D, Wang Y (2013b) Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-kappaB activation and cytokine production of glial cells. Neurosci Lett 534:123-127
251. Zhang YC, Gan FF, Shelar SB, Ng KY, Chew EH (2013c) Antioxidant and Nrf2 inducing activities of luteolin, a flavonoid constituent in ixeris sonchifolia hance, provide neuroprotective effects against ischemia-induced cellular injury. Food Chem Toxicol 59:272-280
252. Zheng YQ, Liu JX, Wang JN, Xu L (2007) Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res 1138:86-94
253. Zheng Z, Kim JY, Ma HL, Lee JE, Yenari MA (2008) Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke. J Cereb Blood Flow Metab 28:53-63
254. Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221-225
255. Zhu H, Wang Z, Xing Y, Gao Y, Ma T, Lou L, Lou J, Wang S, Wang Y (2012) Baicalin reduces the permeability of the blood-brain barrier during hypoxia in vitro by increasing the expression of tight junction proteins in brain microvascular endothelial cells. J Ethnopharm 141:714-720
256. Zhuang P, Zhang Y, Cui G, Bian Y, Zhang M, Zhang J, Liu Y, Yang X, Isaiah AO, Lin Y, Jiang Y (2012) Direct stimulation of adult neural stem/progenitor cells in vitro and neurogenesis in vivo by salvianolic acid B. PLoS One 7:e35636
257. Zirlik A, Maier C, Gerdes N, MacFarlane L, Soosairajah J, Bavendiek U, Ahrens I, Ernst S, Bassler N, Missiou A, Patko Z, Aikawa M, Schoenbeck U, Bode C, Libby P, Peter K (2007) CD40 ligand mediates inflammation independently of CD40 by interaction with Mac-1. Circulation 115:1571-1580 (Pubitemid 46648642)