Can Immunotherapy be used to Treat Ischemic Stroke?
Keywords:
Stroke, immunotherapy, ischemia, ischemic injury, inflammation, leukocytes, antibodiesAbstract
There are two kinds of stroke: ischemic stroke and haemorrhagic stroke. Ischemic stroke constitutes about 85% of all stroke cases. In the UK, stroke is the 4th leading cause of death. The available treatment for stroke is intravenous tissular plasminogen activator (ivtPA), but this is not a sufficient therapeutic approach. It needs to be administered 3 hours following stroke, in order to be effective. Moreover, recent findings have implicated tPA to interact with NMDA receptors resulting in noxious effects. As the population ages, more people are likely going to suffer from a stroke. Therefore, it is imperative to find novel therapies for its treatment. This study, through reviewing existing literature on stroke research, explores the possibility of treating ischemic stroke with immunotherapy. This study communicates that there are numerous immunotherapeutic targets in ischemic stroke. But, while animal studies have been very successful, most of this success has failed to translate into clinical success. Immunotherapy remains an exciting option to treat ischemic stroke, however, the best therapeutic approach still remains the administration of ivtPA.
References
J.L. Hinkle & M. Guanci, Acute Ischemic Stroke, Review. J Neurosci Nurs., 39(5), 285-293, 310, 2007.
P. Liao, C.Y. Yu, G. Ng, Therapeutic antibodies in Stroke, Transl. stroke Res., 4, 477-483, 2013.
B.W. McColl, S.M. Allan, N.J. Rothwell, Systemic inflammation and stroke: aetiology, pathology and targets for therapy, Biochem Soc Trans., 35(pt 5), 11633-5, 2007.
H. Offner, A.A. Vandenbark & P.D. Hurn, Effect of experimental stroke on peripheral immunity: CNS ischemia induces profound immunosuppression, Neuroscience, 158(3), 1098-1111, 2009.
T. Wisniewski, & A. Boutajangout, Vaccination as a therapeutic approach for Alzheimer’s disease, Mt Sinai J Med, 77(1), 17-31, 2012.
R.L. Sacco, E.J. Benjamin, J.P. Broderick, M. Dyken, J.D. Easton, W.M. Feinberg, et al, Stroke Risk Factors, Stroke, 28, 1507-1517, 1997.
D.K. Kiely, P.A. Wolf, L.A. Cupples, A.S. Beiser, R.H. Myers, Familial aggregation of stroke: the Framingham Study, Stroke, 24, 1366-1371, 1993.
A. Kumar, R. Sagar, P. Kumr, J.K. Sahu, A. Grover, A.K. Srivastava, et al, Identification of genetic contribution to ischemic stroke by screening of single nucleotide polymorphisms in stroke patients by using a case control study design, BMC Neurol, 13, 136, 2013.
K.L. Furie, S.E. Kasner, R.J. Adams, G.W. Albers, R.L. Bush, S.C. Fagan, et al, Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association, Stroke, 42, 227-276, 2011.
Lobes of the brain, n.d. image from MedlinePlus, viewed 14 April 2014.
S. Ackerman, Discovering the Brain, Washington (DC): National Academies Press (US), Major Structures and Functions of the Brain, 2, 1992.
Z. Vrseija, H. Brkic, S. Mrdenovic, R. Radivoje, G. Curic, Function of circle of Willis, J Cereb Blood Flow Metab., 34(4), 578-584, 2014.
V. Fuster, B. Stein, J.A. Ambrose, L. Badimon, J.J. Badimon, J.H. Chesebro, Atherosclerotic plaque rupture and thrombosis: evolving concepts, Circulation, 82, 47–59, 1990.
T.M. Dudney, C.G. Elliott, Pulmonary embolism from amniotic fluid, fat, and air, Prog. Cardiovasc. Dis., 36, 447–474, 1994.
I. Harukuni & A. Bhardwaj, Mechanisms of brain injury after global cerebral ischemia, Neurol Clin, 24, 1-21, 2006.
K. Hossman, Pathophysiology and therapy of experimental stroke, Cellular and Molecular Neurobiology, 26(7-8), 1057-83, 2006.
K.J. Zu ̈lch, The Cerebral Infarct. Pathology, Pathogenesis, and Computed Tomography, Springer-Verlag, Berlin, Heidelberg, New York, Tokyo, 1985.
U. Dirnagl & W. Pulsinelli, Autoregulation of cerebral blood flow in experimental focal brain ischemia, J. Cereb. Blood Flow Metab., 10, 327–336, 1990.
K.A. Hossmann, Viability thresholds and the penumbra of focal ischemia, Ann. Neurol. 36, 557– 565, 1994b.
G. Mies, T. Iijima, and k.A. Hossmann, K, Correlation between periinfarct DC shifts and ischemic neuronal damage in rat, NeuroReport 4, 709–711, 1993.
R. Gonzalez, Imaging-Guided Acute Ischemic Stroke Therapy: From “Time Is Brain” to “Physiology Is Brain”, Am J Neuroradiol, 27, 728-735, 2006.
J.N. Kew & J.A. Kemp, Ionotropic and metabotropic receptor structure and pharmacology, Psychopharmacology (Berl), 179(1), 4-29, 2005.
P.H. Chan, Role of oxidants in ischemic brain damage. Stroke 27, 1124–1129, 1996.
Y.H. Kim, E.Y. Kim, B.J. Gwag, S. Sohn, and J.Y. Koh, Zinc-induced cortical neuronal death with features of apoptosis and necrosis, mediation by free radicals, Neuroscience 89, 175–182, 1999.
M. Tomita, Pathophysiology of brain edema. In: Kalimo, H. (Ed.), Cerebrovascular Diseases, ISN Neuropath, Basel, Switzerland, 33–46, 2005.
G.Y. Yang, G.P. Schielke, C. Gong, Y. Mao, H.L. Ge, C.H. Liu, and A.L. Betz, Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1 beta converting enzyme deficient mice, J. Cereb. Blood Flow Metab. 19, 1109–1117, 1999.
E. Kolackowska & Kubes, Neutrophil recruitment and function in health and inflammation, Nature reviews Immunology, 13, 159-175, 2013.
E.J. Kunkel & E.C. Butcher, Plasma-cell homing, Nature Reviews Immunology, 3, 822-829, 2003.
O. Barreiro & F. Sanchez-Madrid, Molecular Basis of Leukocyte-Endothelium Interactions During the Inflammatory Response, Rev Esp Cardiol., 62(5), 552-62, 2009.
D.G. Woodside & P. Vanderslice, Cell adhesion antagonists: therapeutic potential in asthma and chronic obstructive disease, Biodrugs, 22(2), 85-100, 2008.
A. Stemer, & P. Lyden, Evolution of the thrombolytic treatment window for acute ischemic stroke, Curr. Neurol. Neurosci. Rep., 10, 29–33, 2010.
W. Hacke, M. Kaste, C. Fieschi, Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke, The European Cooperative Acute Stroke Study (ECASS) JAMA. 274, 1017–1025, 1995.
D. Collen & H.R. Lijnen, History of Discovery: The Tissue-Type Plasminogen Activator Story, Arteriosclorosis, thrombosis, and Vascular Biology, 29, 1151-1155, 2009.
K. Benchenane, H. Castel, M. Boulouard, R. Bluthe, M. Fernaandez-Monreal, B.D. Roussel, et al, Anti-NR1 N-terminal-domain vaccination unmasks the crucial action of tPA on NMDA-receptor-mediated toxicity and spatial memory, J Cell Sci, 120, 578-585, 2007.
H. Takeda, M. Spatz, C. Ruetzler, R. McCarron, K. Becker, J. Hallenbeck, Induction of mucosal tolerance to E-selectin prevents ischemic and hemorrhagic stroke in spontaneously hypertensive genetically stroke- prone rats, Stroke, 33, 2156–63, 2002.
A. Vila-Corcoles, O. Ochoa-Gondar, T. Rodriguez-Blanco, A. Giutierrez-Perez, A. Vila-Rovira, F. Gomez, et al, Clinical effectiveness of pneumococcal vaccination against acute myocardial infarction and stroke in people over 60 years: the CAPAMIS study, one-year follow-up, BMC Public Health, 12, 222, 2012.
T. GrandPre, F. Nakamura, T. Vartanian, S.M. Strittmatter, Identification of the Nogo inhibitor of axon regeneration as a reticulon protein, Nature, 403, 439–44, 2000.
S.Y. Tsai, T.M. Markus, E.M. Andrews, L. Cheatwood, A.J. Emerick, A.K. Mir, et al, Intrathecal treatment with anti-Nogo-A antibody improves functional recovery in adult rats after stroke, Exp Brain Res., 182, 261–6, 2007.
Ma, J., Tian, W., M., Hou, S., P., Xu, Q., Y., Spector, M., Cui, F., Z. 2007. An experi- mental test of stroke recovery by implanting a hyaluronic acid hy- drogel carrying a Nogo receptor antibody in a rat model. Biomed Mater., 2, 233–40.
J. Zhang & J.S. Diamond, Distinct perisynaptic and synaptic localisation of NMDA and AMPA receptors on ganglion cells in rat retina, J Comp Neurol., 498(6), 810-820, 2006.
W. Paschen, Disturbances of calcium homeostasis within the endoplasmic reticulum may contribute to the development of ischemic- cell damage, Med. Hypotheses, 47, 283–288, 1996.
M.J. During, C.W. Symes, P.A. Lawlor, J. Lin, J. Dunning, H.L. Fitzsimons, et al, An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy, Science, 287, 1453–60, 2000.
R. Macrez, P. Obiang, M. Gauberti, B. Roussel, A. Baron, J. Parcq, et al, Antibodies preventing the interaction of tissue-type plasminogen activator with N -methyl-D -aspartate receptors reduce stroke damages and extend the therapeutic window of thrombolysis, Stroke, 42, 2315–22, 2011.
Y. Matsuo, T. Kihara, M. Ikeda, M. Ninomiya, H. Onodera, K. Kogure, Role of neutrophils in radical production during ischemia and reper- fusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation, J Cereb Blood Flow Metab., 15, 941–7, 1995.
Y. Matsuo, H. Onodera, Y. Shiga, M. Nakamura, M. Ninomiya, T. Kihara, et al, Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion, Stroke, 25, 1469–75, 1994.
H. Suzuki, K. Abe, S.J. Tojo, H. Kitagawa, K. Kimura, M. Mizugaki, et al, Reduction of ischemic brain injury by anti-P-selectin monoclo- nal antibody after permanent middle cerebral artery occlusion in rat, Neurol Res., 21, 269–76, 1999.
J. Huang, T.F. Choudhri, C.J. Winfree, R.A. McTaggart, S. Kiss, J. Mocco, et al, Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke, Stroke, 31, 3047–53, 2000.
Bednar, M., M., Gross, C., E., Russell, S., R., Fuller, S., P., Ellenberger, C., L., Schindler, E., et al. 1998. Humanized anti-L-selectin monoclonal antibody DREG200 therapy in acute thromboembolic stroke. Neurol Res., 20, 403–8, 1998.
R.L. Zhang, M. Chopp, N. Jiang, W.X. Tang, J. Prostak, A.M. Manning, et al, Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not perma- nent middle cerebral artery occlusion in the Wistar rat, Stroke, 26, 1438–42, 1995.
M. Chopp, Y. Li, N. Jiang, R.L. Zhang, J. Prostak, Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain, J Cereb Blood Flow Metab, 16, 578–84, 1996.
M.K.T. Squier, A.J. Sehnert, J.J. Cohen, Apoptosis in leukocytes, J Leuk Biol, 57, 2–10, 1995.
H.H. Birdsall, Induction of ICAM-1 on human neural cells and mechanisms of neutrophil-mediated injury, Am J Pathol, 139, 1341–1350, 1991.
M.P. Bowes, R. Rothlein, S.C. Fagan, J.A. Zivin, Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic in- jury and enhance efficacy of thrombolytic therapy, Neurology, 45, 815–9, 1995.
M. Chopp, R.L. Zhang, H. Chen, Y. Li, N. Jiang, J.R. Rusche, Postischemic administration of an anti-Mac-1 antibody reduces is- chemic cell damage after transient middle cerebral artery occlusion in rats, Stroke, 25, 869–75, 1994.
J. Hill, T. Lindsay, J. Rusche, C.R. Valeri, D. Shepro, H.B. Hechtman, A mac-1 antibody reduces liver and lung injury but not neutrophil sequestration after intestinal ischemia-reperfusion, Surgery, 112, 166-172, 1992.
Y. Yamasaki, Y. Matsuo, J. Zagorski, N. Matsuura, H. Onodera, Y. Itoyama, et al, New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats, Brain Res., 759, 103–11, 1997.
A.J. Bruce, W. Boling, M.S. Kindy, M, J. Peschon, P.J. Kraemer, M.K. Carpenter, F.W. Holtsberg & M.P. Mattson, Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors, Nat Med, 2, 788−794, 1996.
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