Progress in the identification of stroke-related genes: Emerging new possibilities to develop concepts in stroke therapy

CNS Drugs

Volumn 19, Issue 10, 2005, Pages 821-832

  Lippoldt, Andrea ^a   Reichel, Andreas ^a   Moenning, Ursula ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; CALCIUM CHANNEL BLOCKING AGENT; CHEMOKINE; CYTOKINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EPROSARTAN; GROWTH FACTOR; HYDROCHLOROTHIAZIDE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INDAPAMIDE; LOSARTAN; NITRENDIPINE; PERINDOPRIL; PRAVASTATIN; SIMVASTATIN;

BLOOD BRAIN BARRIER; BRAIN ISCHEMIA; CLINICAL TRIAL; CYTOKINE PRODUCTION; DRUG APPROVAL; ENCEPHALITIS; GENE EXPRESSION; GENE IDENTIFICATION; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETIC SUSCEPTIBILITY; HUMAN; HYPERTENSION; MACROPHAGE; MICROGLIA; NERVE CELL LESION; NERVE CELL NECROSIS; NERVE CELL PLASTICITY; NERVE REGENERATION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROPHYLAXIS; REVIEW; STROKE;

ANIMALS; CEREBROVASCULAR ACCIDENT; DISEASE MODELS, ANIMAL; HUMANS; INFLAMMATION; NERVE REGENERATION;

EID: 31344460428     PISSN: 11727047     EISSN: 11727047     Source Type: Journal    
DOI: 10.2165/00023210-200519100-00002     Document Type: Review

References (180)

1. American Heart Assocation. Heart and stroke facts statistics: 1999 statistical supplement. Dallas (TX): American Heart Association, 1999
2. Adelman SM. The national survey of stroke: economic impact. Stroke 1981; 12: 169-87
3. Taylor TN, Davis PH, Torner JC, et al. Lifetime cost of stroke in the United States. Stroke 1996; 27: 1459-66
4. Evers S, Struijs JN, Ament AJHA, et al. International compari-son of stroke cost studies. Stroke 2004; 35: 1209-15
5. Aslanyan S, Weir CJ, Lees KR, et al. Effect of area-based deprivation on the severity, subtype, and outcome of ischemic stroke. Stroke 2003; 34: 2623-8
6. Carr FJ, McBride MW, Carswell HV, et al. Genetic aspects of stroke: human and experimental studies. J Cereb Blood Flow Metab 2002; 22: 767-73
7. Alberts MJ. Stroke genetics update. Stroke 2003; 34: 342-4
8. Hassan A, Markus HS. Genetics and ischemic stroke. Brain 2000; 123: 1784-812
9. Legos JJ, Tuma RF, Barone FC. Pharmacological interventions for stroke: failures and future. Expert Opin Investig Drugs 2002; 11 (5): 603-14
10. Fisher M, Brott TG. Emerging therapies for acute ischemic stroke: new therapies on trial. Stroke 2003; 34: 359-61
11. Legos JJ, Barone FC. Update on pharmacological strategies for stroke: prevention, acute intervention and regeneration. Curr Opin Investig Drugs 2003; 4: 847-58
12. Zheng Z, Lee JE, Yenari MA. Stroke: molecular mechanisms and potential targets for treatment. Curr Mol Med 2003; 3: 361-72
13. Schwartz M. Macrophages and microglia in central nervous system injury: are they helpful or harmful? J Cereb Blood Flow Metab 2003; 23: 385-94
14. Carmichael ST. Gene expression changes after focal stroke, traumatic brain and spinal cord injuries. Curr Opin Neurol 2003; 16: 699-704
15. Hallbergson AF, Gnatenco C, Peterson DA. Neurogenesis and brain injury: managing a renewable resource for repair. J Clin Invest 2003; 112: 1128-33
16. Zhang W, Stanimirovic D. Current and future therapeutic strategies to target inflammation in stroke. Curr Drug Targets Inflamm Allergy 2002 Jun; 1 (2): 151-66
17. Gladstone DJ, Black SE, Hakim AM. Toward wisdom from failure: lessons from neuroprotective stroke trials and new therapeutic directions. Stroke 2002; 33: 2123-36
18. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 1999 Sep; 22 (9): 391-7
19. Stoll G, Jander S, Schroeter M. Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system. Adv Exp Med Biol 2002; 513: 87-113
20. Arnett HA, Wang Y, Matsushima GK, et al. Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. J Neurosci 2003; 23: 9824-32
21. Batchelor PE, Porritt MJ, Martinello P, et al. Macrophages and microglia produce local trophic gradients that stimulate axonal sprouting toward but not beyond the wound edge. Mol Cell Neurosci 2002 Nov; 21 (3): 436-53
22. Shaked I, Porat Z, Gersner R, et al. Early activation of microglia as antigen-presenting cells correlate with T-cell mediated protection and repair of the injured CNS. J Neuroimmunol 2004; 146: 84-93
23. Marchetti B, Abbracchio MP. To be or not to be (inflamed) - is that the question in anti-inflammatory drug therapy of neurodegenerative disorders? In press
24. Han HS, Yenari MA. Cellular targets of brain inflammation in stroke. Curr Opin Investig Drugs 2003; 4: 522-9
25. Barlow C, Lockhardt DJ. DANN arrays and neurobiology-what's new and what's next? Curr Opin Neurobiol 2002; 12: 554-61
26. Bates S, Read SJ, Harrison DC, et al. Characterisation of gene expression changes following permanent MCAO in the rat using subtractive hybridisation. Brain Res Mol Brain Res 2001; 93: 70-80
27. Trendelenburg G, Prass K, Priller J, et al. Serial analysis of gene expression idetifies metallothionein-II as a major neuroprotec-tive gene in mouse focal cerebral ischemia. J Neurosci 2002; 22: 5879-88
28. Kim YD, Sohn NW, Kang C, et al. DNA array reveals altered gene expression in response to focal cerebral ischemia. Brain Res Bull 2002; 58: 491-8
29. Read SJ, Parsons AA, Harrison DC, et al. Stroke genomics: approaches to identify, validate, and understand ischemic stroke gene expression. J Cereb Blood Flow Metab 2001 Jul; 21 (7): 755-78
30. Bond BC, Virley DJ, Cairns NJ, et al. The quantification of gene expression in an animal model of brain ischemia using TaqMan real-time RT-PCR. Brain Res Mol Brain Res 2002; 106: 101-16
31. Schmidt-Kastner R, Zhang B, Belayev L, et al. DNA Microarray analysis of cortical gene expression during early recirculation after focal brain ischemia in rat. Brain Res Mol Brain Res 2002; 108: 81-93
32. Lu A, Tang Y, Ran R, et al. Genomics of the periinfarction cortex after focal cerebral ischemia. J Cereb Blood Flow Metab 2003 Jul; 23 (7): 786-810
33. Raghavendra Rao VL, Bowen KK, Dhodda VK, et al. Gene expression analysis of spontaneously hypertensive rat cerebral cortex following transient focal cerebral ischemia. J Neurochem 2002; 83: 1072-86
34. Berti R, Williams AJ, Moffet JR, et al. Quantitative real-time RT-PCR analysis of inflammatory gene expression associated with ischemia-reperfusion brain injury. J Cereb Blood Flow Metab 2002; 22: 1068-79
35. Jin K, Mao XO, Eshoo MW, et al. Microarray analysis of hippocampal gene expression in global cerebral ischemia. Ann Neurol 2001; 50: 93-103
36. Roth A, Gill R, Certa U. Temporal and spatial gene expression patterns after experimental stroke in a rat model and characterization of PC4, a potential regulator of transcription. Mol Cell Neurosci 2003; 22: 353-64
37. Tang Y, Lu A, Aronow BJ, et al. Genomic responses of the brain to ischemic stroke, intracerebral hemorrhage, kainate seizures, hypoglycemia, and hypoxia. Eur J Neurosci 2002; 15: 1937-52
38. Schwarz DA, Barry G, Mackay KB, et al. Identification of differentially expressed genes induced by transient ischemic stroke. Brain Res Mol Brain Res 2002; 101: 12-22
39. Kitagawa K, Matsumoto M, Hori M. Protective and regenerative response endogenously induced in the ischemic brain. Can J Physiol Pharmacol 2001 Mar; 79 (3): 262-5
40. Liberto CM, Albrecht PJ, Herx LM, et al. Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem 2004; 89: 1092-100
41. Rothwell N. Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential. Brain Behav Immun 2003; 17 (3): 152-7
42. Touzani O, Boutin H, LeFeuvre R, et al. Interleukin-1 influences ischemic brain damage in the mouse independently of the interleukin-1 type I receptor. J Neurosci 2002; 22 (1): 38-43
43. Boutin H, LeFeuvre RA, Horaiu R, et al. Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci 2001; 21 (15): 5528-34
44. Allan SM, Pinteauc E. The interleukin-1 system: an attractive and viable therapeutic target in neurodegenerative disease. Curr Drug Targets CNS Neurol Disord 2003; 2 (5): 293-302
45. Allan SM. Pragmatic target discovery from novel gene to functionally defined drug target: the interleukin-1 story. Methods Mol Med 2004; 104: 333-46
46. Vila N, Castillo J, Davalos A, et al. Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 2000; 31: 2325-9
47. Kito T, Kuroda E, Yokota A, et al. Cytotoxicity in glioma cells due to interleukin-12 and interleukin-18-stimulated macrophages mediated by interferon-gamma-regulated nitric oxide. J Neurosurg 2003 Feb; 98 (2): 385-92
48. Lee YB, Nagai A, Kim SU. Cytokines, chemokines, and cytokine receptors in human microglia. J Neurosci Res 2002 Jul 1; 69 (1): 94-103
49. Kouwenhoven M, Carlstrom C, Ozenci V, et al. Metal-loproteinase and cytokine profiles in monocytes over the course of stroke. J Clin Immunol 2001 Sep; 21 (5): 365-75
50. Hallenbeck JM. The many faces of tumor necrosis factor in stroke. Nat Med 2002; 8 (12): 1363-8
51. Minami M, Satoh M. Chemokines and their receptors in the brain: pathophysiological roles in ischemic brain injury. Life Sci 2003; 74: 312-27
52. Wang L, Li Y, Chen X, et al. MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture. Hematology 2002; 7 (2): 113-7
53. Küry P, Schroeter M, Jander S. Transcriptional response to cumscribed cortical brain ischemia: spatiotemporal patterns in ischemic vs remote non-ischemic cortex. Eur J Neurosci 2004; 19: 1708-20
54. Wang X, Li X, Yaish-Ohad S, et al. Molecular cloning and expression of the rat monocyte chemotactic protein-3 gene: a possible role in stroke. Brain Res Mol Brain Res 1999; 71 (2): 304-12
55. Kremlev SG, Roberts RL, Palmer C. Differential expression of chemokines and chemokine receptors during microglial activation and inhibition. J Neuroimmunol 2004; 149 (1-2): 1-9
56. Hill WD, Hess DC, Martin-Studdard A, et al. SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol 2004; 63 (1): 84-96
57. Tarazzo G, Campanella M, Ghiani M, et al. Expression of fractalkine and its receptor, CX3CR1, in response to ischemia-reperfusion brain injury in the rat. Eur J Neurosci 2002; 15: 1663-8
58. Wang X, Li X, Schmidt DB, et al. Identification and molecular characterization of rat CXCR3: receptor expression and interferon-inducible protein-10 binding are increased in focal stroke. Mol Pharmacol 2000; 57: 1190-8
59. Bajetto A, Bonavia R, Barbero S, et al. Characterization of chemokines and their receptors in the central nervous system: physiopathological implications. J Neurochem 2002 Sep; 82 (6): 1311-29
60. Krathwohl MD, Kaiser JL. Chemokines promote quiescence and survival of human neural progenitor cells. Stem Cells 2004; 22 (1): 109-18
61. Lu M, Grove EA, Miller RJ. Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci U S A 2002 May 14; 99 (10): 7090-5
62. Ji JF, He BP, Dheen ST, et al. Expression of chemokine receptors CXCR4, CCR2, CCR5 and CX3CR1 in neural progenitor cells isolated from the subventricular zone of the adult rat brain. Neurosci Lett 2004 Jan 30; 355 (3): 236-40
63. Guan J, Miller OT, Waugh KM, et al. Insulin-like growth factor-1 improves somatosensory function and reduces the extent of cortical infarction and ongoing neuronal loss after hypoxia-ischemia in rats. Neuroscience 2001; 105 (2): 299-306
64. Smith PF. Neuroprotection against hypoxia-ischemia by insulin-like growth factor-I (IGF-I). IDrugs 2003; 6 (12): 1173-7
65. Dempsey RJ, Sailor KA, Bowen KK, et al. Stroke-induced progenitor cell proliferation in adult spontaneously hypertensive rat brain: effect of exogenous IGF-1 and GDNF. J Neurochem 2003; 87 (3): 586-97
66. Ay I, Sugimori H, Finkelstein SP. Intravenous basic fibroblast growth factor (bFGF) decreases DANN fragmentation and prevents downregulation of Bcl-2 expression in the ischemic brain following middle cerebral artery occlusion in rats. Brain Res Mol Brain Res 2001; 87 (1): 71-80
67. Sugimori H, Speller H, Finklestein SP. Intravenous basic fibroblast growth factor produces a persistent reduction in infarct volume following permanent focal ischemia in rats. Neurosci Lett 2001; 300 (1): 13-6
68. Ma J, Qiu J, Hirt L, et al. Synergistic protective effect of caspase inhibitors and bFGF against brain injury induced by transient focal ischemia. Br J Pharmacol 2001; 133 (3): 345-50
69. Lippoldt A, Andbjer B, Rosen L, et al. Photochemically induced focal cerebral ischemia in rat: time dependent and global increase in expression of basic fibroblast growth factor mRNA. Brain Res 1993; 625 (1): 45-56
70. Wada K, Sugimori H, Bhide PG, et al. Effect of basic fibroblast growth factor treatment on brain progenitor cells after permanent focal ischemia in rats. Stroke 2003; 34 (11): 2722-8
71. Nakatomi H, Kuriu T, Okabe S, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 2002; 110 (4): 429-41
72. Song BW, Vinters HV, Wu D, et al. Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjugation to a blood-brain barrier delivery vector. J Pharmacol Exp Ther 2002; 301 (2): 605-10
73. Hermann DM, Kilic E, Kugler S, et al. Adenovirus-mediated GDNF and CNTF pretreatment protects against striatal injury following transient middle cerebral artery occlusion in mice. Neurobiol Dis 2001; 8 (4): 655-66
74. Bates B, Hirt L, Thomas SS, et al. Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress: possible involvement of oxygen free radicals. Neurobiol Dis 2002; 9 (1): 24-37
75. Endres M, Fan G, Hirt L, et al. Stroke damage in mice after knocking the neurotrophin-4 gene into the brain-derived neurotrophic factor locus. J Cereb Blood Flow Metab 2003; 23 (2): 150153
76. Ferrer I, Krupinsky J, Goutan E, et al. Brain-derived neurotrophic factor reduces cortical cell death by ischemia after middle cerebral artery occlusion in the rat. Acta Neuropathol (Berl) 2001; 101 (3): 229-38
77. Kurozumi K, Nakamura K, Tamiya T, et al. BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model. Mol Ther 2004; 9 (2): 189-97
78. Gustafsson E, Andsberg G, Darsalia V, et al. Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus in-creases neuronal death but promotes neurogenic response following stroke. Eur J Neurosci 2003; 17 (12): 2667-78
79. Yamagata K, Tagami M, Ikeda K, et al. Differential regulation of glial cell line-derived neurotrophic factor (GDNF) mRNA expression during hypoxia and reoxygenation in astrocytes isolated from stroke-prone spontaneously hypertensive rats. Glia 2002; 37 (1): 1-7
80. Arvidsson A, Kokaia Z, Airkasinen MS, et al. Stroke induces widespread changes of gene expression for glial cell line-derived neurotrophic factor family receptors in the adult rat brain. Neuroscience 2001; 106 (1): 27-41
81. Zhang WR, Hayashi T, Iwai M, et al. Time dependent amelioration against ischemic brain damage by glial cell line-derived neurotrophic factor after middle cerebral artery occlusion in rat. Brain Res 2001; 903 (1-2): 253-6
82. Justizia C, Perez-Asensio FJ, Burguete MC, et al. Administration of transforming growth factor-alpha reduces infarct volume after transient focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 2001; 21 (9): 1097-104
83. Stoll G, Schroeter M, Jander S, et al. Lesion-associated expression of transforming growth factor-beta-2 in the rat nervous system: evidence for down-regulating the phagocytotic activity of microglia and macrophages. Brain Pathol 2004; 14 (1): 51-8
84. Buisson A, Lesne S, Docagne F, et al. Transforming growth factor-beta and ischemic brain injury. Cell Mol Neurobiol 2003; 23 (4-5): 539-50
85. Zhu Y, Yang GY, Ahlemeyer B, et al. Transforming growth factor-beta 1 increases bad phosphorylation and protects neurons against damage. J Neurosci 2002; 22 (10): 3898-909
86. Fagan SC, Hess DC, Machado LS, et al. Tactics for vascular protection after acute ischemic stroke. Pharmacoptherapy 2005; 25: 387-95
87. Harvey BK, Hoffer BJ, Wang Y. Stroke and TGF-beta proteins: glial cell line-derived neurotrophic factor and bone morphogenetic protein. Pharmacol Ther 2005; 105: 113-25
88. Sun Y, Jin K, Xie L, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 2003; 111 (12): 1843-51
89. Alzheimer C, Werner S. Fibroblast growth factor and neuroprotection. Adv Exp Med Biol 2002; 513: 335-51
90. Vemuganti R, Dempsey RJ, Bowen KK. Inhibition of intercellular adhesion molecule-1 protein expression by antisense oligonucleotides is neuroprotective after transient middle cerebral artery occlusion in rat. Stroke 2004 Jan; 35 (1): 179-84
91. Ishikawa M, Cooper D, Russell J, et al. Molecular determinants of the prothrombogenic and inflammatory phenotype assumed by the postischemic cerebral microcirculation. Stroke 2003 Jul; 34 (7): 1777-82
92. Justicia C, Panes J, Sole S, et al. Neutrophil infiltration increases matrix metalloproteinase-9 in the ischemic brain after occlusion/reperfusion of the middle cerebral artery in rats. J Cereb Blood Flow Metab 2003 Dec; 23 (12): 1430-40
93. Danton GH, Dietrich WD. Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol 2003 Feb; 62 (2): 127-36
94. Stoll G, Jander S, Schroeter M. Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system. Adv Exp Med Biol 2002; 513: 87-113
95. Aldskogius H. Regulation of microglia-potential new drug targets in the CNS. Expert Opin Ther Targets 2001; 5: 655-68
96. Cajal SR. Degeneration and regeneration of the nervous system. Vols 1 & 2. Translated by May RM. London: Oxford University Press, 1928
97. Choi YS, Lee MY, Sung KW, et al. Regional differences in enhanced neurogenesis in the dentate gyrus of adult rats after transient forebrain ischemia. Mol Cells 2003 Oct; 16 (2): 232-8
98. Kokaia Z, Lindvall O. Neurogenesis after ischemic brain insults. Curr Opin Neurobiol 2003 Feb; 13 (1): 127-32
99. Yagita Y, Kitagawa K, Sasaki T, et al. Differential expression of Musashi1 and nestin in the adult rat hippocampus after ischemia. J Neurosci Res 2002 Sep; 69 (6): 750-6
100. Sharp FR, Liu J, Barnabeu R. Neurogenesis following brain ischemia. Brain Res Dev Brain Res 2002 Mar; 134 (1-2): 23-30
101. Takasawa K, Kitagawa K, Yagita Y, et al. Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats. J Cereb Blood Flow Metab 2002 Mar; 22 (3): 299-307
102. Yagita Y, Kitagawa K, Ohtsuki T, et al. Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke 2001 Aug; 32 (8): 1890-6
103. Jin K, Miami M, Lan JQ, et al. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci U S A 2001 Apr; 98 (8): 4710-5
104. Parent JM. Injury-induced neurogenesis in the adult mammalian brain. Neuroscientist 2003 Aug; 9 (4): 261-72
105. Parent JM, Vexler ZS, Gong C, et al. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 2002 Dec; 52 (6): 802-13
106. Jin K, Sun Y, Xie L, et al. Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci 2003; 24: 171-89
107. Jiang W, Gu W, Brannstrom T, et al. Cortical neurogenesis in adult rats after transient middle cerebral artery occlusion. Stroke 2001 May; 32 (5): 1201-7
108. Gu W, Brannstrom T, Wester P. Cortical neurogenesis in adult rats after reversible photothrombotic stroke. J Cereb Blood Flow Metab 2000 Aug; 20 (8): 1166-73
109. Arlotta P, Magavi SS, Macklis JD. Induction of adult neurogenesis: molecular manipulation of neural precursors in situ. Ann N Y Acad Sci 2003 Jun; 991: 229-36
110. Felling RJ, Levison SW. Enhanced neurogenesis following stroke. J Neurosci Res 2003; 73: 277-83
111. Nakatomi H, Kuriu T, Okabe S, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 2002 Aug; 110 (4): 429-41
112. Teramoto T, Qiu J, Plumier JC, et al. EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia. J Clin Invest 2003; 111: 1125-32
113. Sailor KA, Dhodda VK, Rao VL, et al. Osteopontin infusion into normal adult rat brain fails to increase cell proliferation in dentate gyrus and subventricular zone. Acta Neurochir Suppl 2003; 86: 181-5
114. Wang X, Louden C, Yue TL, et al. Delayed expression of osteopontin after focal stroke in the rat. J Neurosci 1998 Mar; 18 (6): 2075-83
115. Ellison JA, Barone FC, Feuerstein GZ. Matrix remodeling after stroke: de novo expression of matrix proteins and integrin receptors. Ann N Y Acad Sci 1999; 890: 204-22
116. Gustafsson E, Lindvall O, Kokaia Z. Intraventricular infusion of TrkB-Fc fusion protein promotes ischemia-induced neurogenesis in adult rat dentate gyrus. Stroke 2003; 34: 2710-5
117. Sun Y, Jin K, Xie L, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 2003; 111: 1843-51
118. Zhu DY, Liu SH, Sun HS, et al. Expression of inducible nitric oxide synthetase after focal cerebral ischemia stimulates neurogenesis in the adult rodent dentate gyrus. J Neurosci 2003; 23: 223-9
119. Uchida K, Kumihashi K, Kurosawa S, et al. Stimulatory effects of prostaglandin E2 on neurogenesis in the dentate gyrus of the adult rat. Zoolog Sci 2002; 19: 1211-6
120. Sasaki T, Kitagawa K, Sugiura S, et al. Implication of cycloox-ygenase-2 on enhanced proliferation of neural progenitor cells in the adult mouse hippocampus after ischemia. J Neurosci Res 2003; 72: 461-71
121. Kumihashi K, Uchida K, Miyazaki H, et al. Acetylsalicylic acid reduces ischemia-induced proliferation of dentate cells in gerbils. Neuroreport 2001; 12: 915-7
122. Arvidsson A, Kokaia Z, Lindvall O. N-methy-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke. Eur J Neurosci 2001 Jul; 14 (1): 10-8
123. Villoslada P, Genain CP. Role of nerve growth factor and other trophic factors in brain inflammation. Prog Brain Res 2004; 146: 403-14
124. Morganti-Kossmann MC, Rancan M, Stahel PF, et al. Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr Opin Crit Care 2002 Apr; 8 (2): 101-5
125. Piehl F, Lidman O. Neuroinflammation in the rat-CNS cells and their role in the regulation of immune reactions. Immunol Rev 2001 Dec; 184: 212-25
126. Liao SL, Chen WY, Raung SL, et al. Association of immune responses and ischemic brain infarction in rat. Neuroreport 2001 Jul; 12 (9): 1943-7
127. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19: 312-8
128. Bezzi P, Domercq M, Brambilla L, et al. CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci 2001 Jul; 4 (7): 702-10
129. Ekdahl CT, Claasen JH, Bonde S, et al. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A 2003; 100: 13632-7
130. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003; 302: 1760-5
131. Batchelor PE, Porritt MJ, Nilsson SK, et al. Periwound dopaminergic sprouting is dependent on numbers of wound macrophages. Eur J Neurosci 2002 Mar; 15 (5): 826-32
132. Otten U, Marz P, Heese K, et al. Cytokines and neurotrophins interact in normal and diseased states. Ann N Y Acad Sci 2000; 917: 322-30
133. Hallenbeck JM. The many faces of tumor necrosis factor in stroke. Nat Med 2002 Dec; 8 (12): 1363-8
134. Iliev AI, Stringaris AK, Nau R, et al. Neuronal injury mediated via stimulation of microglial toll-like receptor 9 (TLR9). FASEB J 2004 Feb; 18 (2): 412-4
135. Han HS, Karabiyikoglu M, Kelly S, et al. Mild hyperthermia inhibits nuclear factor-kappaB translocation in experimental stroke. J Cereb Blood Flow Metab 2003 May; 23 (5): 589-98
136. Cai Z, Pang Y, Lin S, et al. Differential roles of tumor necrosis factor-alpha and interleukin-1 beta in lipopolysaccharide-in-duced brain injury in the neonatal rat. Brain Res 2003 Jun; 975 (1-2): 37-47
137. Schroeter M, Kury P, Jander S. Inflammatory gene expression in focal cortical brain ischemia-differences between rats and mice. Brain Res Mol Brain Res 2003 Sep; 117 (1): 1-7
138. Tomimoto H, Ihara M, Wakita H, et al. Chronic cerebral hypoperfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat. Acta Neuropathol (Berlin) 2003 Dec; 106 (6): 527-34
139. Arnett HA, Mason J, Marino M, et al. TNF alpha promotes prolieration of oligodendrocyte progenitors and remyelination. Nat Neurosci 2001; 4: 1116-22
140. Ferrer I, Planas AM. Signaling of cell death and cell survival following focal cerebral ischemia: life and death struggle in the penumbra. J Neuropathol Exp Neurol 2003 Apr; 62 (4): 329-39
141. Belayev L, Busto R, Zhao W, et al. Middle cerebral artery occlusion in the mouse by intraluminal suture coated with poly-L-lysine: neurological and histological validation. Brain Res 1999 Jul; 833 (2): 181-90
142. Aspey BS, Cohen S, Patel Y, et al. Middle cerebral artery occlusion in the rat: consietent protocol for a model of stroke. Neuropathol Appl Neurobiol 1998 Dec; 24 (6): 487-97
143. Takano K, Tatlisumak T, Bergmann AG, et al. Reproducibility and reliability of middle cerebral artery occlusion using a silicone-coated suture (Koizumi) in rats. J Neurol Sci 1997 Dec; 153 (1): 8-11
144. Pevsner PH, Eichenbaum JW, Miller DC, et al. A photothrombotic model of small early ischemic infarcts in the rat brain with histologic and MRI correlation. J Pharmacol Toxicol Methods 2001 May-Jun; 45 (3): 227-33
145. Callaway JK, Knight MJ, Watkins DJ, et al. A novel, rapid, computerized method for quantification of neuronal damage in a rat model of stroke. J Neurosci Methods 2000 Oct; 102 (1): 53-60
146. Yamory Y. Implication of hypertensive rat models for primordial nutrition prevention of cardiovascular diseases. Clin Exp Pharmacol Physiol 1999 Jul; 26 (7): 568-72
147. Yamori Y. Predictive and preventive pathology of cardiovascular diseases. Acta Pathol Jpn 1989 Nov; 39 (11): 683-705
148. Kiprov D. Experimental models of hypertension. Cor Vasa 1970; 22 (1-2): 116-28
149. Meng X, Fisher M, Shen Q, et al. Characterizing the diffusion/perfusion mismatch in experimental focal cerebral ischemia. Ann Neurol 2004 Feb; 55 (2): 207-12
150. Tsuchiya D, Hong S, Kayama T, et al. Effect of suture size and carotid clip application upon blood flow and infarct volume after permanent and temporary middle cerebral artery occlusion in mice. Brain Res 2003 Apr; 970 (1-2): 131-9
151. Badan I, Platt D, Kessler C, et al. Temporal dynamics of degenerative and regenerative events associated with cerebral ischemia in aged rats. Gerontology 2003; 49: 356-65
152. Abraham CS, Harada N, Deli MA, et al. Transient forebrain ischemia increases the blood-brain barrier permeability for albumin in stroke.prone spontaneously hypertensive rats. Cell Mol Neurobiol 2002 Aug; 22 (4): 455-62
153. Takemori K, Ito H, Suzuki T. Effects of the AT1 receptor antagonist on adhesion molecule expression in leukocytes and brain microvessels of stroke-prone spontaneously hypertensive rats. Am J Hypertens 2000 Nov; 13 (11): 1233-41
154. Hazama F, Chue CH, Kataoka H, et al. Pathogenesis of lacuna-like cyst formation and diffuse degeneration of the white matter in the brain of stroke.prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol Suppl 1995 Dec; 22 (1): S260-1
155. Fredriksson K, Nordborg C, Kalimo H, et al. Cerebral microangiopathy in stroke-prone spontaneously hypertensive rats: an immunohistochemical and ultrastructural study. Acta Neuropathol (Berl) 1988; 75 (3): 241-52
156. Clark JB, Palmer J, Shaw WN. The diabetic Zucker fatty rat (41611). Proc Soc Exp Biol Med 1983; 173: 68-75
157. Kurtz TW, Morris RC, Pershadsingh HA. The Zucker fatty rat as a genetic model of obesity and hypertension. Hypertension 1989; 13: 897-901
158. Lippoldt A, Kniesel U, Liebner S, et al. Structural alterations of tight junctions are associated with loss of polarity in stroke-prone spontaneously hypertensive rat blood-brain barrier endothelial cells. Brain Res 2000 Dec; 885 (2): 251-61
159. Absher PM, Hendley E, Jaworski DM, et al. Impairment of the blood-brain barrier: a potential surrogate delineating the determinants of cerebral bleeding caused by fibrinolytic drugs. Coron Artery Dis 1999 Sep; 10 (6): 413-20
160. Wennberg R, Zimmermann C. The PROGRESS trial three years later: time for a balanced report of effectiveness. BMJ 2004; 329: 968-9
161. MacMahon S, Neal B, Rodgers A, et al. Commentary: The PROGRESS trial three years later: time for more action, less distraction. BMJ 2004; 329: 970-1
162. Schrader J, Lüders S, Kulschewski A, et al. Morbidiy and mortality after stroke: eprosartan compared with nitrendipine for secondary prevention. Stroke 2005; 36: 1218-26
163. Bennai F, Morsing P, Paliege A, et al. Normalizing the expression of nitric oxide synthase by low-dose AT1 receptor antagonism parallels improved vascular morphology in hypertensive rats. J Am Soc Nephrol 1999 Jan; 10 Suppl. 11: S104-15
164. Takahashi M, Fritz-Zieroth B, Ohta Y, et al. Therapeutic effects of imidapril on cerebral lesions observed with magnetic resonance imaging in malignant stroke-prone spontaneously hypertensive rats. J Hypertens 1994 Jul; 12 (7): 761-8
165. Hankey GJ. Angiotensin-converting enzyme inhibitors for stroke prevention: is there HOPE for PROGRESS after LIFE? Stroke 2003; 34: 354-6
166. Dahlof B, Burke TA, Kronot K, et al. Population impact of losartan use on stroke in the European Union (EU): projections from the Losartan intervention for endpoint reduction in hypertension (LIFE) study. J Hum Hypertens 2004; 18/6: 367-73
167. Devereux RB, Lyle PA. Losartan for the treatment of hypertension and left ventricular hypertrophy: the losartan intervention for endpoint reduction in hypertension (LIFE) study. Expert Opin Pharmacother 2004; 5/11: 2311-20
168. SCRIP. Leader in world pharmaceutical news [newsletter]. 2003; 2837: 20
169. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastin Survival Study (4S). Scandanavian Simvastatin Survival Study Group. Lancet 1994; 344: 1383-9
170. Pederson TR, Kjekshus J, Pyörälä K, et al. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian Simvastin Survival Study (4S). Am J Cardiol 1998; 81: 333-5
171. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after MI in patients with average cholesterol levels. New Engl J Med 1996; 335: 1001-9
172. Plehn JF, Davis PR, Sacks FM, et al. Reduction of stroke incidence after myocardial infarction with pravastatin: the cholesterol and recurrent events (CARE) study. Circ 1999; 99: 216-23
173. White HD, Simes RJ, Anderson NE, et al. Pravastatin therapy and the risk of stroke. New Eng J Med 2000; 343: 317-26
174. Long-term effectiveness and safety of prvastatin in 9014 patients with coronary heart disease and average choldesterol concentrations: the LIPID trial follow-up. The LIPID Study Group. Lancet 2000; 359: 1379-87
175. Deanfield JE. Clinical trials: evidence and unanswered questions-hyperlipidaemia. Cerebrovasc Dis 2003; 16 Suppl. 3: 25-32
176. Marti-Fabregas J, Gomis M, Abroix A, et al. Favorable outcome of ischemic stroke in patients pretreated with statins. Stroke 2004; 35: 1117-23
177. The SPARCL investigators. Design and baseline characteristics of the stroke prevention by aggressive reduction of cholesterol levels (SPARCL) study. Cerebrovasc Dis 2003; 16: 389-95
178. Gorelick PB. Stroke prevention therapy beyond antithrombotics: unifying mechanisms in ischemic stroke pathogenesis and implications for therapy. Stroke 2002; 33: 862-75
179. Emsley HCA, Tyrrell PJ. Inflammation and infection in clinical stroke. J Cereb Blood Flow Metab 2002; 22: 1399-419
180. Mancia G. Prevention and treatment of stroke in patients with hypertension. Clin Ther 2004; 26/5: 631-48