Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Cardiovascular Translational Research
Published in: Journal of Cardiovascular Translational Research 5/2013

01-10-2013

Role of Inflammation and Its Mediators in Acute Ischemic Stroke

Published in: Journal of Cardiovascular Translational Research | Issue 5/2013

Login to get access

Abstract

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies.
Literature
1.
Wang, X. (2005). Investigational anti-inflammatory agents for the treatment of ischemic brain injury. Expert Opinion on Investigational Drugs, 14, 393–409.PubMed
2.
Barone, F. C., & Feuerstein, G. Z. (1999). Inflammatory mediators and stroke: new opportunities for novel therapeutics. Journal of Cerebral Blood Flow and Metabolism, 19, 819–834.PubMed
3.
Chamorro, A., & Hallenbeck, J. (2006). The harms and benefits of inflammatory and immune responses in vascular disease. Stroke, 37, 291–293.PubMed
4.
Samson, Y., Lapergue, B., & Hosseini, H. (2005). Inflammation and ischaemic stroke: current status and future perspectives. Reviews Neurology (Paris), 161, 1177–1182.
5.
Yilmaz, G., & Granger, D. N. (2008). Cell adhesion molecules and ischemic stroke. Neurological Research, 30, 783–793.PubMed
6.
Emsley, H. C., & Hopkins, S. J. (2008). Acute ischaemic stroke and infection: recent and emerging concepts. Lancet Neurology, 7, 341–353.PubMed
7.
McColl, B. W., Allan, S. M., & Rothwell, N. J. (2009). Systemic infection, inflammation and acute ischemic stroke. Neuroscience, 158, 1049–1061.PubMed
8.
Jin, R., Yang, G., & Li, G. (2010). Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. Journal of Leukocyte Biology, 87, 779–89.PubMed
9.
Iadecola, C., & Anrather, J. (2011). The immunology of stroke: from mechanisms to translation. Nature Medicine, 17, 796–808.PubMed
10.
Hallenbeck, J. M. (1996). Significance of the inflammatory response in brain ischemia. Acta Neurochirurgica. Supplement, 66, 27–31.PubMed
11.
Chopp, M., Li, Y., Jiang, N., Zhang, R. L., & Prostak, J. (1996). Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. Journal of Cerebral Blood Flow and Metabolism, 16, 578–584.PubMed
12.
Connolly, E. S., Jr., Winfree, C. J., Prestigiacomo, C. J., Kim, S. C., Choudhri, T. F., Hoh, B. L., et al. (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. Circulation Research, 81, 304–310.PubMed
13.
Garau, A., Bertini, R., Colotta, F., Casilli, F., Bigini, P., Cagnotto, A., et al. (2005). Neuroprotection with the CXCL8 inhibitor repertaxin in transient brain ischemia. Cytokine, 30, 125–131.PubMed
14.
Yenari, M. A., Kunis, D., Sun, G. H., Onley, D., Watson, L., Turner, S., et al. (1998). Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia. Experimental Neurology, 153, 223–233.PubMed
15.
Zheng, Z., & Yenari, M. A. (2004). Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurological Research, 26, 884–892.PubMed
16.
Barone, F. C., Arvin, B., White, R. F., Miller, A., Webb, C. L., Lysko, P. G., et al. (1997). Tumor necrosis factor-α: a mediator of focal ischemic brain injury. Stroke, 28, 1233–1244.PubMed
17.
Rothwell, N., Allan, S., & Toulmond, S. (1997). The role of interleukin 1 in acute neurodegeneration and stroke: pathophysiological and therapeutic implications. Journal of Clinical Investigation, 100, 2648–2652.PubMed
18.
Felger, J. C., Abe, T., Kaunzner, U. W., Gottfried-Blackmore, A., Gal-Toth, J., McEwen, B. S., et al. (2010). Brain dendritic cells in ischemic stroke: time course, activation state, and origin. Brain, Behavior, and Immunity, 24, 724–737.PubMed
19.
Tanaka, R., Komine-Kobayashi, M., Mochizuki, H., Yamada, M., Furuya, T., Migita, M., et al. (2003). Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia. Neuroscience, 117, 531–539.PubMed
20.
Konsman, J. P., Drukarch, B., & Van Dam, A. M. (2007). (Peri)vascular production and action of pro-inflammatory cytokines in brain pathology. Clinical Science (London, England), 112, 1–25.
21.
Shigematsu, T., Wolf, R. E., & Granger, D. N. (2002). T-lymphocytes modulate the microvascular and inflammatory responses to intestinal ischemia–reperfusion. Microcirculation, 9, 99–109.PubMed
22.
Zwacka, R. M., Zhang, Y., Halldorson, J., Schlossberg, H., Dudus, L., & Engelhardt, J. F. (1997). CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver. Journal of Clinical Investigation, 100, 279–289.PubMed
23.
Yilmaz, G., Arumugam, T. V., Stokes, K. Y., & Granger, D. N. (2006). Role of T lymphocytes and interferon-γ in ischemic stroke. Circulation, 113, 2105–2112.PubMed
24.
Kreutzberg, G. W. (1996). Microglia: a sensor for pathological events in the CNS. Trends in Neurosciences, 19, 312–318.PubMed
25.
Thomas, W. E. (1992). Brain macrophages: evaluation of microglia and their functions. Brain Research, 17, 61–74.PubMed
26.
Lalancette-Hébert, M., Gowing, G., Simard, A., Weng, Y. C., & Kriz, J. (2007). Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. Journal of Neuroscience, 27, 2596–2605.PubMed
27.
Lai, A. Y., & Todd, K. G. (2006). Microglia in cerebral ischemia: molecular actions and interactions. Canadian Journal of Physiology and Pharmacology, 84, 49–59.PubMed
28.
Denes, A., Vidyasagar, R., Feng, J., Narvainen, J., McColl, B. W., Kauppi-nen, R. A., et al. (2007). Proliferating resident microglia after focal cerebral ischaemia in mice. Journal of Cerebral Blood Flow and Metabolism, 27, 1941–1953.PubMed
29.
George, B., Robin, E., White, Y. O., Lijun, X., & Giffard, G. R. (2011). Astrocytes: targets for neuroprotection in stroke. Central Nervous System Agents in Medicinal Chemistry, 11, 164–173.
30.
Nowicka, D., Rogozinska, K., Aleksy, M., Witte, O. W., & Skangiel-Kramska, J. (2008). Spatiotemporal dynamics of astroglial and microglial responses after photothrombotic stroke in the rat brain. Acta Neurobiologiae Experimentalis (Wars), 68, 155–168.
31.
Zhu, Y., Roth-Eichhorn, S., Braun, N., Culmsee, C., Rami, A., & Krieglstein, J. (2000). The expression of transforming growth factor-beta1 (TGF-beta1) in hippocampal neurons: a temporary upregulated protein level after transient forebrain ischemia in the rat. Brain Research, 866, 286–298.PubMed
32.
Benveniste, E. N. (1998). Cytokine actions in the central nervous system. Cytokine & Growth Factor Reviews, 9, 259–275.
33.
Che, X., Ye, W., Panga, L., Wu, D. C., & Yang, G. Y. (2001). Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice. Brain Research, 902, 171–177.PubMed
34.
Dong, Y., & Benveniste, E. N. (2001). Immune function of astrocytes. Glia, 36, 180–190.PubMed
35.
Wang, W., Redecker, C., Yu, Z. Y., Xie, M. J., Tian, D. S., Zhang, L., et al. (2008). Rat focal cerebral ischemia induced astrocyte proliferation and delayed neuronal death are attenuated by cyclin-dependent kinase inhibition. Journal of Clinical Neuroscience, 15, 278–285.PubMed
36.
Sharif, A., Legendre, P., Prevot, V., Allet, C., Romao, L., Studler, J. M., et al. (2007). Transforming growth factor alpha promotes sequential conversion of mature astrocytes into neural progenitors and stem cells. Oncogene, 26, 2695–2706.PubMed
37.
Justicia, C., Perez-Asensio, F. J., Burguete, M. C., Salom, J. B., & Planas, A. M. (2001). Administration of transforming growth factor-alpha reduces infarct volume after transient focal cerebral ischemia in the rat. Journal of Cerebral Blood Flow and Metabolism, 21, 1097–1104.PubMed
38.
Meistrell, M. E., 3rd, Botchkina, G. I., Wang, H., Di Santo, E., Cockroft, K. M., Bloom, O., et al. (1997). Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia. Shock, 8, 341–348.PubMed
39.
Barger, S. W., Horster, D., Furukawa, K., Goodman, Y., Krieglstein, J., & Mattson, M. P. (1996). Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation. Proceedings of the National Academy of Sciences of the United States of America, 92, 9328–9332.
40.
Lambertsen, K. L., Clausen, B. H., Babcock, A. A., Gregersen, R., Fenger, C., Nielsen, H. H., et al. (2009). Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. Journal of Neuroscience, 29, 1319–1330.PubMed
41.
Boutin, H., LeFeuvre, R. A., Horai, R., Asano, M., Iwakura, Y., & Rothwell, N. J. (2001). Role of IL-1alpha and IL-1beta in ischemic brain damage. Journal of Neuroscience, 21, 5528–5534.PubMed
42.
Yamasaki, Y., Matsuura, N., Shozuhara, H., Onodera, H., Itoyama, Y., & Kogure, K. (1995). Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke, 26, 676–680.PubMed
43.
Loddick, S. A., Turnbull, A. V., & Rothwell, N. J. (1998). Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. Journal of Cerebral Blood Flow and Metabolism, 18, 176–179.PubMed
44.
Stamatovic, S. M., Shakui, P., Keep, R. F., Moore, B. B., Kunkel, S. L., Van, R. N., et al. (2005). Monocyte chemoattractant protein-1 regulation of blood–brain barrier permeability. Journal of Cerebral Blood Flow and Metabolism, 25, 593–606.PubMed
45.
Soriano, S. G., Amaravadi, L. S., Wang, Y. F., Zhou, H., Yu, G. X., Tonra, J. R., et al. (2002). Mice deficient in fractalkine are less susceptible to cerebral ischemia–reperfusion injury. Journal of Neuroimmunology, 125, 59–65.PubMed
46.
Spera, P. A., Ellison, J. A., Feuerstein, G. Z., & Barone, F. C. (1998). IL-10 reduces rat brain injury following focal stroke. Neuroscience Letters, 251, 189–192.PubMed
47.
Ooboshi, H., Ibayashi, S., Shichita, T., Kumai, Y., Takada, J., & Ago, T. (2005). Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia. Circulation, 111, 913–919.PubMed
48.
Pang, L., Ye, W., Che, X. M., Roessler, B. J., Betz, A. L., & Yang, G. Y. (2001). Reduction of inflammatory response in the mouse brain with adenoviral-mediated transforming growth factor-ss1 expression. Stroke, 32, 544–552.PubMed
49.
Ruocco, A., Nicole, O., Docagne, F., Ali, C., Chazalviel, L., Komesli, S., et al. (1999). A transforming growth factor-b antagonist unmasks the neuroprotective role of this endogenous cytokine in excitotoxic and ischemic brain injury. Journal of Cerebral Blood Flow and Metabolism, 19, 1345–1353.PubMed
50.
Zhang, Y., Wei, X., Liu, L., Liu, S., Wang, Z., Zhang, B., et al. (2012). TIPE2, a novel regulator of immunity, protects against experimental stroke. Journal of Biological Chemistry, 287, 32546–32555.PubMed
51.
Kooijman, R., Sarre, S., Michotte, Y., & Keyser, D. J. (2009). Insulin-like growth factor I: a potential neuroprotective compound for the treatment of acute ischemic stroke? Stroke, 404, e83–88.
52.
Denti, L., Annoni, V., Cattadori, E., Salvagnini, M. A., Visioli, S., & Merli, M. F. (2004). Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly. American Journal of Medicine, 117, 312–317.PubMed
53.
Liu, T., Clark, R. K., McDonnell, P. C., Young, P. R., White, R. F., & Barone, F. C. (1994). Tumor necrosis factor-α expression in ischemic neurons. Stroke, 25, 1481–1488.PubMed
54.
Wang, X., Yue, T. L., Barone, F. C., White, R. F., Gagnon, R. C., & Feuerstein, G. Z. (1994). Concomitant cortical expression of TNF-α and IL-1 α mRNAs follows early response gene expression in transient focal ischemia. Molecular and Chemical Neuropathology, 23, 103–114.PubMed
55.
Murakami, Y., Saito, K., Hara, A., Zhu, Y., Sudo, K., Niwa, M., et al. (2005). Increases in tumor necrosis factor-alpha following transient global cerebral ischemia do not contribute to neuron death in mouse hippocampus. Journal of Neurochemistry, 93, 1616–1622.PubMed
56.
Offner, H., Subramanian, S., Parker, S. M., Afentoulis, M. E., Vandenbark, A. A., & Hurn, P. D. (2006). Experimental stroke induces massive, rapid activation of the peripheral immune system. Journal of Cerebral Blood Flow and Metabolism, 26, 654–665.PubMed
57.
Hallenbeck, J. M. (2002). The many faces of tumor necrosis factor in stroke. Nature Medicine, 8, 1363–1368.PubMed
58.
Ginis, I., Jaiswal, R., Klimanis, D., Liu, J., Greenspon, J., & Hallenbeck, J. M. (2002). TNF-alpha-induced tolerance to ischemic injury involves differential control of NF-kappaB transactivation: the role of NF-kappaB association with p300 adaptor. Journal of Cerebral Blood Flow and Metabolism, 22, 142–152.PubMed
59.
Alikhani, M., Alikhani, Z., Raptis, M., & Graves, D. T. J. (2004). TNF-alpha in vivo stimulates apoptosis in fibroblasts through caspase-8 activation and modulates the expression of pro-apoptotic genes. Cell Physiology, 201, 341–348.
60.
Plumpe, J., Malek, N. K., Bock, C. T., Rakemann, T., Manns, M. P., & Trautwein, C. (2000). NF-kappaB determines between apoptosis and proliferation in hepatocytes during liver regeneration. American Journal of Physiology—Gastrointestinal and Liver Physiology, 278, 173–183.
61.
Zeng, L., Liu, J., Wang, Y., Wang, L., Weng, S., Chen, S., et al. (2012). Cocktail blood biomarkers: prediction of clinical outcomes in patients with acute ischemic stroke. European Neurology, 69(2), 68–75.PubMed
62.
Thornberry, N. A., Bull, H. G., Calaycay, J. R., Chapman, K. T., Howard, A. D., & Kostura, M. J. (1992). A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature, 356, 768–774.PubMed
63.
Dinarello, C. A. (1996). Biologic basis for interleukin-1 in disease. Blood, 15, 2095–2147.
64.
Black, R. A., Kronheim, S. R., & Sleath, P. R. (1989). Activation of interleukin-1β by a co-induced protease. FEBS Letters, 247, 386–390.PubMed
65.
Schonbeck, V., Mach, F., & Libby, P. (1998). Generation of biologically active IL-1β by matrix metalloproteinase a novel caspase-1 independent pathway of IL-1β processing. Journal of Immunology, 161, 3340–3346.
66.
Dinarello, C. A., & Wolff, S. M. (1993). The role of interleukin-1 in disease. New England Journal of Medicine, 328, 106–113.PubMed
67.
Bankers-Fulbright, J. L., Kalli, K. R., & McLean, D. J. (1996). IL-1 signal transduction. Life Sciences, 59, 61–83.PubMed
68.
Rothwell, N. J., & Luheshi, G. N. (2000). Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends in Neurosciences, 23, 618–625.PubMed
69.
Koga, S., Ogawa, S., Kuwabara, K., Brett, J., Leavy, J. A., & Ryan, J. (1992). Synthesis and release of interleukin 1 by reoxygenated human mononuclear phagocytes. Journal of Clinical Investigation, 90, 1007–1015.PubMed
70.
Basu, A., Lazovic, J., Krady, J. K., Mauger, D. T., Rothstein, R. P., Smith, M. B., et al. (2005). Interleukin-1 and the interleukin-1 type 1 receptor are essential for the progressive neurodegeneration that ensues subsequent to a mild hypoxic/ischemic injury. Journal of Cerebral Blood Flow and Metabolism, 25, 17–29.PubMed
71.
Herrmann, O., Tarabin, V., Suzuki, S., Attigah, N., Coserea, I., & Schneider, A. (2003). Regulation of body temperature and neuroprotection by endogenous interleukin-6 in cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism, 23, 406–415.PubMed
72.
Waje-Andreassen, U., Kråkenes, J., Ulvestad, E., Thomassen, L., Myhr, K. M., Aarseth, J., et al. (2005). IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurologica Scandinavica, 111, 360–365.PubMed
73.
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (1813). The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochimica et Biophysica Acta, 2011, 878–888.
74.
Connolly, E. S. J., Winfree, C. J., Springer, T. A., Naka, Y., Liao, H., & Yan, S. D. (1996). Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke. Journal of Clinical Investigation, 97, 209–16.PubMed
75.
Moore, K. L., Eaton, S. F., Lyons, D. E., Lichenstein, H. S., Cummings, R. D., & McEver, R. P. (1994). The P-selectin glycoprotein ligand from human neutrophils displays sialylated, fucosylated, O-linked poly-N-acetyllactosamine. Journal of Biological Chemistry, 269, 23318–23327.PubMed
76.
Stenberg, P. E., Shuman, M. A., Levine, S. P., & Bainton, D. F. (1984). Redistribution of alpha-granules and their contents in thrombin-stimulated platelets. Journal of Cell Biology, 98, 748–760.PubMed
77.
Bargatze, R. F., Kurk, S., Butcher, E. C., & Jutila, M. A. (1994). Neutrophils roll on adherent neutrophils bound to cytokine-induced endothelial cells via L-selectin on the rolling cells. Journal of Experimental Medicine, 180, 1785–1792.PubMed
78.
Mayadas, T. N., Johnson, R. C., Rayburn, H., Hynes, R. O., & Wagner, D. D. (1993). Leukocyte rolling and extravasation are severely compromised in P-selectin deficient mice. Cell, 74, 541–554.PubMed
79.
Huang, J., Kim, L. J., Mealey, R., Marsh, H. C., Zhang, Y., Tenner, A. J., et al. (1999). Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein. Science, 285, 595–599.PubMed
80.
Huang, J., Choudhri, T. F., Winfree, C. J., McTaggart, R. A., Kiss, S., Mocco, J., et al. (2000). Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke. Stroke, 31, 3047–3053.PubMed
81.
Mocco, J., Choudhri, T., Huang, J., Harfeldt, E., Efros, L., Klingbeil, C., et al. (2002). HuEP5C7 as a humanized monoclonal anti-E/P-selectin neurovascular protective strategy in a blinded placebo-controlled trial of nonhuman primate stroke. Circulation Research, 91, 907–914.PubMed
82.
Lehmberg, J., Beck, J., Baethmann, A., & Uhl, E. (2006). Effect of P-selectin inhibition on leukocyte endothelium interaction and survival after global cerebral ischemia. Journal of Neurology, 253, 357–363.PubMed
83.
Cha, J. K., Jeong, M. H., Kim, E. K., Lim, Y. J., Ha, B. R., & Kim, S. H. (2002). Surface expression of P-selectin on platelets is related with clinical worsening in acute ischemic stroke. Journal of Korean Medical Science, 17, 811–816.PubMed
84.
Zhao, D. X., Feng, J., Cong, S. Y., & Zhang, W. (2012). Association of E-selectin gene polymorphisms with ischemic stroke in a Chinese Han population. Journal of Neuroscience Research, 90, 1782–1787.PubMed
85.
Kaba, N. K., Schultz, J., Law, F. Y., Lefort, C. T., Martel-Gallegos, G., Kim, M., et al. (2008). Inhibition of Na+/H+ exchanger enhances low pH-induced L-selectin shedding and beta2-integrin surface expression in human neutrophils. American Journal of Physiology. Cell Physiology, 295, C1454–1463.PubMed
86.
Springer, T. A. (1990). Adhesion receptors of the immune system. Nature, 346, 425.PubMed
87.
Gahmberg, C. G. M., Tolvanen, P., & Kotovuori. (1997). Leukocyte adhesion: structure and function of human leukocyte β2-integrins and their cellular ligands. European Journal of Biochemistry, 245, 215–232.PubMed
88.
Diacovo, T. G., de Fougerolles, A. R., Bainton, D. F., & Springer, T. A. (1994). A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2. Journal of Clinical Investigation, 94, 1243–1251.PubMed
89.
Zhang, R. L., Chopp, M., Chen, H., & Garcia, J. H. (1994). Temporal profile of ischemic tissue damage, neutrophil response, and vascular plugging following permanent and transient (2H) middle cerebral artery occlusion in the rat. Journal of Neurological Sciences, 125, 3–10.
90.
Kanemoto, Y., Nakase, H., Akita, N., & Sakaki, T. (2002). Effects of anti-intercellular adhesion molecule-1 antibody on reperfusion injury induced by late reperfusion in the rat middle cerebral artery occlusion model. Neurosurgery, 51, 1034–1041.PubMed
91.
Kitagawa, K., Matsumoto, M., Mabuchi, T., Yagita, Y., Ohtsuki, T., Hori, M., et al. (1998). Deficiency of intercellular adhesion molecule 1 attenuates microcirculatory disturbance and infarction size in focal cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism, 18, 1336–1345.PubMed
92.
Khan, M., Jatana, M., Elango, C., Singh, P. A., Singh, A. K., & Singh, I. (2006). Cerebrovascular protection by various nitric oxide donors in rats after experimental stroke. Nitric Oxide, 15, 114–124.PubMed
93.
Vemuganti, R., Dempsey, R. J., & Bowen, K. K. (2004). Inhibition of intercellular adhesion molecule-1 protein expression by antisense oligonucleotides is neuroprotective after transient middle cerebral artery occlusion in rat. Stroke, 35, 179–184.PubMed
94.
Shyu, K. G., Chang, H., & Lin, C. C. (1997). Serum levels of intercellular adhesion molecule-1 and E-selectin in patients with acute ischaemic stroke. Journal of Neurology, 244, 90–93.PubMed
95.
Lindsberg, P. J., Carpen, O., Paetau, A., Karjalainen-Lindsberg, M. L., & Kaste, M. (1996). Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation, 94, 939–945.PubMed
96.
Enlimomab, A. S. T. (2001). Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology, 57, 1428–1434.
97.
Vuorte, J., Lindsberg, P. J., Kaste, M., Meri, S., Jansson, S. E., Rothlein, R., et al. (1999). Anti-ICAM-1 monoclonal antibody R6.5 (Enlimomab) promotes activation of neutrophils in whole blood. Journal of Immunology, 162, 2353–2357.
98.
Zhang, L. H., & Wei, E. Q. (2003). Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on transient global cerebral ischemia in rats. Acta Pharmacologica Sinica, 24, 1241–1247.PubMed
99.
Justicia, C., Martin, A., Rojas, S., Gironella, M., Cervera, A., Panes, J., et al. (2006). Anti-VCAM-1 antibodies did not protect against ischemic damage either in rats or in mice. Journal of Cerebral Blood Flow and Metabolism, 26, 421–432.PubMed
100.
Bajetto, A., Bonavia, R., Barbero, S., Florio, T., & Schettini, G. (2001). Chemokines and their receptors in the central nervous system. Frontiers in Neuroendocrinology, 22, 147–184.PubMed
101.
Chen, Y., Hallenbeck, J. M., Ruetzler, C., Bol, D., Thomas, K., Berman, N. E., et al. (2003). Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates ischemic brain injury and is associated with recruitment of inflammatory cells. Journal of Cerebral Blood Flow and Metabolism, 23, 748–755.PubMed
102.
Lambertsen, K. L., Biber, K., & Finsen, B. (2012). Inflammatory cytokines in experimental and human stroke. Journal of Cerebral Blood Flow and Metabolism, 32, 1677–1698.PubMed
103.
Wang, L., Li, Y., Chen, X., Chen, J., Gautam, S. C., Xu, Y., et al. (2002). MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture. Hematology, 7, 113–117.PubMed
104.
Wang, L., Li, Y., Chen, J., Gautam, S. C., Zhang, Z., Lu, M., et al. (2002). Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture. Experimental Hematology, 30, 831–836.PubMed
105.
Lee, S. R., Kim, H. Y., Rogowska, J., Zhao, B. Q., Bhide, P., Parent, J. M., et al. (2006). Involvement of matrix metalloproteinase in neuroblast cell migration from the subventricular zone after stroke. Journal of Neuroscience, 26, 3491–3495.PubMed
106.
Zhao, B. Q., Wang, S., Kim, H. Y., Storrie, H., Rosen, B. R., Mooney, D. J., et al. (2006). Role of matrix metalloproteinases in delayed cortical responses after stroke. Nature Medicine, 12, 441–445.PubMed
107.
Rosenberg, G. A., Navratil, M., Barone, F., & Feuerstein, G. (1996). Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. Journal of Cerebral Blood Flow and Metabolism, 16, 360–366.PubMed
108.
Clark, A. W., Krekoski, C. A., Bou, S. S., Chapman, K. R., & Edwards, D. R. (1997). Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia. Neuroscience Letters, 238, 53–56.PubMed
109.
Castellanos, M., Leira, R., Serena, J., Pumar, J. M., Lizasoain, I., & Castillo, J. (2003). Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke, 34, 40–46.PubMed
110.
Montaner, J., Alvarez-Sabin, J., Molina, C., Angles, A., Abilleira, S., & Arenillas, J. (2001). Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke, 32, 1759–1766.PubMed
111.
Asahi, M., Wang, X., Mori, T., Sumii, T., Jung, J. C., Moskowitz, M. A., et al. (2001). Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood–brain barrier and white matter components after cerebral ischemia. Journal of Neuroscience, 21, 7724–32.PubMed
112.
Tarkowski, E., Rosengren, L., Blomstrand, C., Wikkelso, C., Jensen, C., Ekholm, S., et al. (1997). Intrathecal release of pro- and anti-inflammatory cytokines during stroke. Clinical and Experimental Immunology, 110, 492–499.PubMed
113.
Pelidou, S. H., Kostulas, N., Matusevicius, D., Kivisakk, P., Kostulas, V., & Link, H. (1999). High levels of IL-10 secreting cells are present in blood in cerebrovascular diseases. European Journal of Neurology, 6, 437–442.PubMed
114.
Strle, K., Zhou, J. H., Shen, W. H., Broussard, S. R., Johnson, R. W., Freund, G. G., et al. (2001). Interleukin-10 in the brain. Critical Reviews in Immunology, 21, 427–449.PubMed
115.
Grilli, M., Barbieri, I., Basudev, H., Brusa, R., Casati, C., Lozza, G., et al. (2000). Interleukin-10 modulates neuronal threshold of vulnerability to ischaemic damage. European Journal of Neuroscience, 12, 2265–2272.PubMed
116.
Kim, J. S., Yoon, S. S., Kim, Y. H., & Ryu, J. S. (1996). Serial measurement of interleukin-6, transforming growth factor-beta, and S 100 protein in patients with acute stroke. Stroke, 27, 1553–1557.PubMed
117.
van Exel, E., Gussekloo, J., de Craen, A. J., Bootsma-van, D. W. A., Frolich, M., & Westendorp, R. G. (2002). Inflammation and stroke: the Leiden 85-Plus Study. Stroke, 33, 1135–1138.PubMed
118.
Buckwalter, M., & Wyss-Coray, T. (2004). Modelling neuroinflammatory phenotypes in vivo. Journal of Neuroinflammation, 1, 10.PubMed
119.
Klempt, N. D., Sirimanne, E., Gunn, A. J., Klempt, M., Singh, K., & Williams, C. (1992). Hypoxia–ischemia induces transforming growth factor beta 1 mRNA in the infant rat brain. Molecular Brain Research, 13, 93–101.PubMed
120.
Wienner, C., Gehrmann, J., Lindholm, D., Topper, R., Kreutzberg, G. W., & Hossmann, K. A. (1993). Expression of transforming growth factor-beta1 and interleukin-1 beta mRNA in rat brain following transient fore-brain ischemia. Acta Neuropathologica, 86, 439–46.
121.
Johnston, R. E., Dillon-Carter, O., Freed, W. J., & Borlongan, C. V. (2001). Trophic factor secreting kidney cell lines: in vitro characterization and functional effects following transplantation in ischemic rats. Brain Research, 900, 268–276.PubMed
122.
Sun, H., Gong, S., Carmody, R. J., Hilliard, A., Li, L., Sun, J., et al. (2008). TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell, 133, 415–426.PubMed
123.
Zhang, X., Wang, J., Fan, C., Li, H., Sun, H., Gong, S., et al. (2009). Crystal structure of TIPE2 provides insights into immune homeostasis. Nature Structural and Molecular Biology, 16, 89–90.PubMed
124.
Kooijman, R. (2006). Regulation of apoptosis by insulin-like growth factor (IGF)-I. Cytokine & Growth Factor Reviews, 17, 305–323.
125.
Liu, X. F., Fawcett, J. R., Hanson, L. R., & Frey, W. H. (2004). The window of opportunity for treatment of focal cerebral ischemic damage with noninvasive intranasal insulin-like growth factor-I in rats. Journal of Stroke and Cerebrovascular Diseases, 13, 16–23.PubMed
126.
Liu, X. F., Fawcett, J. R., Thorne, R. G., DeFor, T. A., & Frey, W. H. (2001). Intranasal administration of insulin-like growth factor-I bypasses the blood–brain barrier and protects against focal cerebral ischemic damage. Journal of Neurological Sciences, 187, 91–97.
127.
De, S. A., Brouns, R., Uyttenboogaart, M., De, R. S., Moens, M., Wilczak, N., et al. (2011). Insulin-like growth factor I serum levels influence ischemic stroke outcome. Stroke, 42, 2180–2185.
128.
Bsibsi, M., Persoon-Deen, C., Verwer, R. W., Meeuwsen, S., Ravid, R., & Van, N. J. M. (2006). Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators. Glia, 53, 688–695.PubMed
129.
Bsibsi, M., Ravid, R., Gveric, D., & Van Noort, J. M. (2002). Broad expression of Toll-like receptors in the human central nervous system. Journal of Neuropathology and Experimental Neurology, 61, 1013–1021.PubMed
130.
Singh, A. K., & Jiang, Y. (2004). How does peripheral lipopolysaccharide induce gene expression in the brain of rats? Toxicology, 201, 197–207.PubMed
131.
Jack, C. S., Arbour, N., Manusow, J., Montgrain, V., Blain, M., McCrea, E., et al. (2005). TLR signaling tailors innate immune responses in human microglia and astrocytes. Journal of Immunology, 175, 4320–4330.
132.
Marsh, B. J., Williams-Karnesky, R. L., & Stenzel-Poore, M. P. (2009). Toll-like receptor signaling in endogenous neuroprotection and stroke. Neuroscience, 158, 1007–1020.PubMed
133.
Sakata, Y., Dong, J. W., Vallejo, J. G., Huang, C. H., Baker, J. S., Tracey, K. J., et al. (2007). Toll-like receptor 2 modulates left ventricular function following ischemia–reperfusion injury. American Journal of Physiology—Heart and Circulatory Physiology, 292, H503–H509.PubMed
134.
Shigeoka, A. A., Holscher, T. D., King, A. J., Hall, F. W., Kiosses, W. B., Tobias, P. S., et al. (2007). TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways. Journal of Immunology, 178, 6252–6258.
135.
Cao, C. X., Yang, Q. W., Lv, F. L., Cui, J., Fu, H. B., & Wang, J. Z. (2007). Reduced cerebral ischemia–reperfusion injury in Toll-like receptor 4 deficient mice. Biochemical and Biophysical Research Communications, 353, 509–514.PubMed
136.
Lehnardt, S., Schott, E., Trimbuch, T., Laubisch, D., Krueger, C., Wulczyn, G., et al. (2008). A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. Journal of Neuroscience, 28, 2320–2331.PubMed
137.
Ziegler, G., Harhausen, D., Schepers, C., Hoffmann, O., Rohr, C., Prinz, V., et al. (2007). TLR2 has a detrimental role in mouse transient focal cerebral ischemia. Biochemical and Biophysical Research Communications, 359, 574–579.PubMed
138.
Caso, J. R., Pradillo, J. M., Hurtado, O., Lorenzo, P., Moro, M. A., & Lizasoain, I. (2007). Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation, 115, 1599–1608.PubMed
139.
Hua, F., Ma, J., Ha, T., Xia, Y., Kelley, J., Williams, D. L., et al. (2007). Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. Journal of Neuroimmunology, 190, 101–111.PubMed
140.
Kinouchi, H., Sharp, F. R., Hill, M. P., Koistinaho, J., Sagar, S. M., & Chan, P. H. (1993). Induction of 70-kDa heat shock protein and hsp70 mRNA following transient focal cerebral ischemia in the rat. Journal of Cerebral Blood Flow and Metabolism, 13, 105–115.PubMed
141.
Faraco, G., Fossati, S., Bianchi, M. E., Patrone, M., Pedrazzi, M., Sparatore, B., et al. (2007). High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo. Journal of Neurochemistry, 103, 590–603.PubMed
142.
Schneider, A., Martin-Villalba, A., Weih, F., Vogel, J., Wirth, T., & Schwaninger, M. (1999). NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nature Medicine, 5, 554–559.PubMed
143.
Liu, H., Xin, L., Chan, B. P. L., Teoh, R., Tang, B. L., & Tan, Y. H. (2002). Interferon beta administration confers a beneficial outcome in a rabbit model of thromboembolic cerebral ischemia. Neuroscience Letters, 327, 146–148.PubMed
144.
Veldhuis, W., Derksen, J., Floris, S., Vander, M. P., de Vries, H., Schepers, J., et al. (2003). Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat. Journal of Cerebral Blood Flow and Metabolism, 23, 1029–1039.PubMed
145.
Bogoyevitch, M. A., Gillespie-Brown, J., Ketterman, A. J., Fuller, S. J., Ben-Levy, R., Ashworth, A., et al. (1996). Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Circulation Research, 79, 162–173.PubMed
146.
Ferrell, J. E. (1996). Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. Trends in Biochemical Sciences, 21, 460–466.PubMed
147.
Davis, R. J. (1993). The mitogen-activated protein kinase signal transduction pathway. Journal of Biological Chemistry, 268, 14553–14556.PubMed
148.
Nithianandarajah-Jones, G. N., Wilm, B., Goldring, C. E., Müller, J., & Cross, M. J. (2012). ERK5: structure, regulation and function. Cellular Signalling, 24, 2187–2196.PubMed
149.
Lewis, T. S., Shapiro, P. S., & Ahn, N. G. (1998). Signal transduction through MAP kinase cascades. Advances in Cancer Research, 74, 49–139.PubMed
150.
Sutton, L. N., Clark, B. J., Norwood, C. R., Woodford, E. J., & Welsh, F. A. (1991). Global cerebral ischemia in piglets under conditions of mild and deep hypothermia. Stroke, 22, 1567–1573.PubMed
151.
Kamme, F., Camp, K., & Wieloch, T. (1995). Biphasic expression of the fos and jun families of transcription factors following transient forebrain ischaemia in the rat. Effect of hypothermia. European Journal of Neuroscience, 7, 2007–2016.PubMed
152.
Wang, Z. Q., Wu, D. C., Huang, F. P., & Yang, G. Y. (2004). Inhibition of MEK/ERK 1/2 pathway reduces pro-inflammatory cytokine interleukin-1 expression in focal cerebral ischemia. Brain Research, 996, 55–66.PubMed
153.
Barnes, P. J. (2010). Mechanisms and resistance in glucocorticoid control of inflammation. Journal of Steroid Biochemistry and Molecular Biology, 120, 6–85.
154.
Woo, C. H., Massett, M. P., Shishido, T., Itoh, S., Ding, B., McClain, C., et al. (2006). ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor delta (PPARdelta) stimulation. Journal of Biological Chemistry, 281, 32164–32174.PubMed
155.
Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., & Greenberg, M. E. (1995). Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science, 270, 1326–1331.PubMed
156.
Kawasaki, H., Morooka, T., Shimohama, S., Kimura, J., Hirano, T., Gotoh, Y., et al. (1997). Activation and involvement of p38 mitogen-activated protein kinase in glutamate-induced apoptosis in rat cerebellar granule cells. Journal of Biological Chemistry, 272, 18518–18521.PubMed
157.
Guan, Q. H., Pei, D. S., Zong, Y. Y., Xu, T. L., & Zhang, G. Y. (2006). Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways. Neuroscience, 139, 609–627.PubMed
158.
Sawe, N., Steinberg, G., & Zhao, H. (2008). Dual roles of the MAPK/ERK1/2 cell signaling pathway after stroke. Journal of Neuroscience Research, 86, 1659–1669.PubMed
159.
Benakis, C., Bonny, C., & Hirt, L. (2010). JNK inhibition and inflammation after cerebral ischemia. Brain, Behavior, and Immunity, 24, 800–811.PubMed
160.
Kaminska, B. (2005). MAPK signalling pathways as molecular targets for anti-inflammatory therapy—from molecular mechanisms to therapeutic benefits. Biochimica et Biophysica Acta, 1754, 253–262.PubMed
161.
Wang, L. W., Tu, Y. F., Huang, C. C., & Ho, C. J. (2012). JNK signaling is the shared pathway linking neuroinflammation, blood–brain barrier disruption, and oligodendroglial apoptosis in the white matter injury of the immature brain. Journal of Neuroinflammation, 17, 175.
162.
Barone, F. C., Irving, E. A., & Ray, A. M. (2001). Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia. Medicinal Research Reviews, 21, 129–145.PubMed
163.
Wang, H., Xu, L., Venkatachalam, S., Trzaskos, J. M., Friedman, S. M., Feuerstein, G. Z., et al. (2001). Differential regulation of IL-1beta and TNF-alpha RNA expression by MEK1 inhibitor after focal cerebral ischemia in mice. Biochemical and Biophysical Research Communications, 286, 869–874.PubMed
164.
Maddahi, A., & Edvinsson, L. (2008). Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway. BMC Neuroscience, 9, 85.PubMed
165.
Alessandrini, A., Namura, S., Moskowitz, M. A., & Bonventre, J. V. (1999). MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proceedings of the National Academy of Sciences of the United States of America, 96, 12866–12869.PubMed
166.
Wang, X., Wang, H., Xu, L., Rozanski, D. J., Sugawara, T., Chan, P. H., et al. (2003). Significant neuroprotection against ischemic brain injury by inhibition of the MEK1 protein kinase in mice: exploration of potential mechanism associated with apoptosis. Journal of Pharmacology and Experimental Therapeutics, 304, 172–178.PubMed
167.
Roux, P. P., & Blenis, J. (2004). ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiology and Molecular Biology Reviews, 68, 320–344.PubMed
168.
Han, B. H., & Holtzman, D. M. (2000). BDNF protects the neonatal brain from hypoxic–ischemic injury in vivo via the ERK pathway. Journal of Neuroscience, 20, 5775–5781.PubMed
169.
Wang, R. M., Zhang, Q. G., Li, J., Yang, L. C., Yang, F., & Brann, D. W. (2009). The ERK5-MEF2C transcription factor pathway contributes to anti-apoptotic effect of cerebral ischemia preconditioning in the hippocampal CA1 region of rats. Brain Research, 1255, 32–41.PubMed
170.
Ridder, D. A., & Schwaninger, M. (2009). NF-kappaB signaling in cerebral ischemia. Neuroscience, 158, 995–1006.PubMed
171.
Napetschnig, J., & Wu, H. (2013). Molecular basis of NF-κB signaling. Annual Review of Biophysics, 42, 443–68.PubMed
172.
Khan, M., Sekhon, B., Giri, S., Jatana, M., Gilg, A. G., Ayasolla, K., et al. (2005). S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke. Journal of Cerebral Blood Flow and Metabolism, 25, 177–192.PubMed
173.
Hill, W. D., Hess, D. C., Carroll, J. E., Wakade, C. G., Howard, E. F., Chen, Q., et al. (2001). The NF-kappaB inhibitor diethyldithiocarbamate (DDTC) increases brain cell death in a transient middle cerebral artery occlusion model of ischemia. Brain Research Bulletin, 55, 375–86.PubMed
174.
Smith, C. J., Emsley, H. C., Vail, A., Georgiou, R. F., Rothwell, N. J., Tyrrell, P. J., et al. (2006). Variability of the systemic acute phase response after ischemic stroke. Journal of Neurological Sciences, 251, 77–81.
175.
Palasik, W., Fiszer, U., Lechowicz, W., Czartoryska, B., Krzesiewicz, M., & Lugowska, A. (2005). Assessment of relations between clinical outcome of ischemic stroke and activity of inflammatory processes in the acute phase based on examination of selected parameters. European Neurology, 53, 188–193.PubMed
176.
McColl, B. W., Rothwell, N. J., & Allan, S. M. (2008). Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice. Journal of Neuroscience, 28, 9451–9462.PubMed
177.
Dandona, P., Aljada, A., & Bandyopadhyay, A. (2004). Inflammation: the link between insulin resistance, obesity and diabetes. Trends in Immunology, 25, 4–7.PubMed
178.
Hansson, G. K., & Libby, P. (2006). The immune response in atherosclerosis: a double-edged sword. Nature Reviews Immunology, 6, 508–519.PubMed
179.
McGill, J. K., Gallagher, L., Carswell, H. V., Irving, E. A., Dominiczak, A. F., & Macrae, I. M. (2005). Impaired functional recovery after stroke in the stroke-prone spontaneously hypertensive rat. Stroke, 36, 135–141.PubMed
180.
Tureyen, K., Kapadia, R., Bowen, K. K., Satriotomo, I., Liang, J., Feinstein, D. L., et al. (2007). Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents. Journal of Neurochemistry, 101, 41–56.PubMed
181.
Warlow, C., Sudlow, C., Dennis, M., Wardlaw, J., & Sandercock, P. (2003). Stroke. Lancet, 362, 1211–1224.PubMed
182.
Krakauer, J. W. (2007). The complex dynamics of stroke onset and progression. Current Opinion in Neurology, 20, 47–50.PubMed
183.
Amantea, D., Nappi, G., Bernardi, G., Bagetta, G., & Corasaniti, M. T. (2009). Post-ischemic brain damage: pathophysiology and role of inflammatory mediators. FEBS Journal, 276, 13–26.PubMed
184.
Kriz, J. (2006). Inflammation in ischemic brain injury: timing is important. Critical Reviews in Neurobiology, 18, 145–157.PubMed
185.
Ruehl, M. L., Orozco, J. A., Stoker, M. B., McDonagh, P. F., Coull, B. M., & Ritter, L. S. (2002). Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion. Neurological Research, 24, 226–232.PubMed
186.
Zhang, R. L., Chopp, M., Jiang, N., Tang, W. X., Prostak, J., Manning, A. M., et al. (1995). Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke, 26, 1438–1442.PubMed
187.
Chopp, M., Zhang, R. L., Chen, H., Li, Y., Jiang, N., & Rusche, J. R. (1994). Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke, 25, 869–875.PubMed
188.
Ma, M., Ma, Y., Yi, X., Guo, R., Zhu, W., Fan, X., et al. (2008). Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone. BMC Neuroscience, 10, 117.
189.
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006). TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity, 24, 179–189.PubMed
190.
Taylor, A., Verhagen, J., Blaser, K., Akdis, M., & Akdis, C. A. (2006). Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology, 117, 433–442.PubMed
191.
Emsley, H. C., Smith, C. J., Georgiou, R. F., Vail, A., Hopkins, S. J., Rothwell, N. J., et al. (2005). Acute stroke investigators: a randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 1366–1372.PubMed
192.
Krams, M., Lees, K. R., Hacke, W., Grieve, A. P., Orgogozo, J. M., & Ford, G. A. (2003). ASTIN Study Investigators. Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN): an adaptive dose–response study of UK-279,276 in acute ischemic stroke. Stroke, 34, 2543–2548.PubMed
193.
Becker, K. J. (2002). Anti-leukocyte antibodies: LeukArrest (Hu23F2G) and Enlimomab (R6.5) in acute stroke. Current Medical Research and Opinion, 18, s18–22.PubMed
194.
Danton, G. H., & Dietrich, W. D. (2003). Inflammatory mechanisms after ischemia and stroke. Neuropathology and Experimental Neurology, 62, 127–136.
195.
Minnerup, J., Sutherland, B. A., Buchan, A. M., & Kleinschnitz, C. (2012). Neuroprotection for stroke: current status and future perspectives. International Journal of Molecular Sciences, 13, 11753–11772.PubMed
196.
Mergenthaler, P., & Meisel, A. (2012). Do stroke models model stroke? Disease Models & Mechanisms, 5, 718–725.
197.
Zaremba, J., & Losy, J. (2001). Early TNF-α levels correlate with ischemic stroke severity. Acta Neurologica Scandinavica, 104, 288–295.PubMed
Metadata
Title
Role of Inflammation and Its Mediators in Acute Ischemic Stroke
Publication date
01-10-2013
Published in
Journal of Cardiovascular Translational Research / Issue 5/2013
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI
https://doi.org/10.1007/s12265-013-9508-6

Other articles of this Issue 5/2013

Journal of Cardiovascular Translational Research 5/2013 Go to the issue

OriginalPaper

Prospective Validation that Vulnerable Plaque Associated with Major Adverse Outcomes Have Larger Plaque Volume, Less Dense Calcium, and More Non-Calcified Plaque by Quantitative, Three-Dimensional Measurements Using Intravascular Ultrasound with Radiofrequency Backscatter Analysis

OriginalPaper

Myocardial Infarction in Sickle Cell Disease: Use of Translational Imaging to Diagnose an Under-Recognized Problem

OriginalPaper

Myocardial Perfusion Imaging with Cardiac Computed Tomography: State of the Art

OriginalPaper

Multi-modality Imaging of the Aortic Valve in the Era of Transcatheter Aortic Valve Replacement: a Guide for Patient Selection, Valve Selection, and Valve Delivery

OriginalPaper

Intramyocardial Injection of Autologous Bone Marrow-Derived Ex Vivo Expanded Mesenchymal Stem Cells in Acute Myocardial Infarction Patients is Feasible and Safe up to 5 Years of Follow-up

OriginalPaper

Coronary Flow Reserve from Mouse to Man—from Mechanistic Understanding to Future Interventions

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits