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Review

Animal models of ischemic stroke and their impact on drug discovery

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Pages 315-326 | Received 23 Oct 2018, Accepted 18 Jan 2019, Published online: 04 Feb 2019

References

  • Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA. 2015;314:1832–1843.
  • Thomalla G, Simonsen CZ, Boutitie F, et al.; WAKE-UP Investigators. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379:611–622.
  • Benjamin EJ, Virani SS, Callaway CW, et al.; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2018 update: a report from the American heart Association. Circulation. 2018;137:e67–e492.
  • Graham SM, McCullough LD, Murphy SJ. Animal models of ischemic stroke: balancing experimental aims and animal care. Comp Med. 2004;54:486–496.
  • Carmichael ST. Rodent models of focal stroke: size, mechanism, and purpose. NeuroRx. 2002;2:396–409.
  • Stroke Therapy Academic Industry Roundtable. Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke. 1999;30:2752–2758.
  • Kilkenny C, Browne W, Cuthill IC, et al., NC3Rs Reporting Guidelines Working Group. Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol. 2010;160:1577–1579.
  • Dirnagl U. ed. Rodent models of stroke. 2nd ed.New York (NY): Springer; 2016. ISSN 0893-2336.
  • Mies G, Ishimaru S, Xie Y, et al. Ischemic thresholds of cerebral protein synthesis and energy state following middle cerebral artery occlusion in rat. J Cereb Blood Flow Metab. 1991;11:753–761.
  • Hata R, Maeda K, Hermann D, et al. Dynamics of regional brain metabolism and gene expression after middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab. 2000;20:306–315.
  • Hata R, Maeda K, Hermann D, et al. Evolution of brain infarction after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 2000;20:937–946.
  • Namura S, Zhu J, Fink K, et al. Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci. 1998;18:3659–3668.
  • Hermann DM, Kilic E, Hata R, et al. Relationship between metabolic dysfunctions, gene responses and delayed cell death after mild focal cerebral ischemia in mice. Neuroscience. 2001;104:947–955.
  • Reitmeir R, Kilic E, Kilic U, et al. Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity. Brain. 2011;134:84–99.
  • Hermann DM, Chopp M. Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation. Lancet Neurol. 2012;11:369–380.
  • Lourbopoulos A, Mamrak U, Roth S, et al. Inadequate food and water intake determine mortality following stroke in mice. J Cereb Blood Flow Metab. 2017;37:2084–2097.
  • Tamura A, Graham DI, McCulloch J. Teasdale GM Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1982;1:53–60.
  • Shigeno T, McCulloch J, Graham DI, et al. Pure cortical ischemia versus striatal ischemia. Circulatory, metabolic, and neuropathologic consequences. Surg Neurol. 1985;24:47–51.
  • Rubino GJ, Young W. Ischemic cortical lesions after permanent occlusion of individual middle cerebral artery branches in rats. Stroke. 1988;19:870–877.
  • Brint S, Jacewicz M, Kiessling M, et al. Focal brain ischemia in the rat: methods for reproducible neocortical infarction using tandem occlusion of the distal middle cerebral and ipsilateral common carotid arteries. J Cereb Blood Flow Metab. 1988;8:474–485.
  • Chen ST, Hsu CY, Hogan EL, et al. A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction. Stroke. 1986;17:738–743.
  • Dietrich WD, Nakayama H, Watson BD, et al. Morphological consequences of early reperfusion following thrombotic or mechanical occlusion of the rat middle cerebral artery. Acta Neuropathol. 1989;78:605–614.
  • Kaplan B, Brint S, Tanabe J, et al. Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia. Stroke. 1991;22:1032–1039.
  • Shigeno T, Teasdale GM, McCulloch J, et al. Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability, and brain edema. J Neurosurg. 1985;63:272–277.
  • Morancho A, García-Bonilla L, Barceló V, et al. A new method for focal transient cerebral ischaemia by distal compression of the middle cerebral artery. Neuropathol Appl Neurobiol. 2012;38:617–627.
  • Robinson MJ, Macrae IM, Todd M, et al. Reduction of local cerebral blood flow to pathological levels by endothelin-1 applied to the middle cerebral artery in the rat. Neurosci Lett. 1990;118:269–272.
  • Wiessner C, Bareyre FM, Allegrini PR, et al. Anti-Nogo-A antibody infusion 24 hours after experimental stroke improved behavioral outcome and corticospinal plasticity in normotensive and spontaneously hypertensive rats. J Cereb Blood Flow Metab. 2003;23:154–165.
  • Watson BD, Dietrich WD, Busto R, et al. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 1985;17:497–504.
  • Dietrich WD, Watson BD, Busto R, et al. Photochemically induced cerebral infarction. I. Early microvascular alterations. Acta Neuropathol. 1987;72:315–325.
  • Clarkson AN, Huang BS, Macisaac SE, et al. Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. Nature. 2010;468:305–309.
  • Minnerup J, Strecker JK, Wachsmuth L, et al. Defining mechanisms of neural plasticity after brainstem ischemia in rats. Ann Neurol. 2018;83:1003–1015.
  • Kuroiwa T, Xi G, Hua Y, et al. Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen. Stroke. 2009;40:248–253.
  • Barth AM, Mody I. Changes in hippocampal neuronal activity during and after unilateral selective hippocampal ischemia in vivo. J Neurosci. 2011;31:851–860.
  • Wester P, Watson BD, Prado R, et al. A photothrombotic ‘ring’ model of rat stroke-in-evolution displaying putative penumbral inversion. Stroke. 1995;26:444–450.
  • Gerriets T, Li F, Silva MD, et al. The macrosphere model: evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats. J Neurosci Meth. 2003;122:201–211.
  • Miyake K, Takeo S, Kaijihara H. Sustained decrease in brain regional blood flow after microsphere embolism in rats. Stroke. 1993;24:415–420.
  • Kudo M, Aoyama A, Ichimori S, et al. An animal model of cerebral infarction. Homologous blood clot emboli in rats. Stroke. 1982;13:505–508.
  • Kilic E, Hermann DM. Hossmann KA A reproducible model of thromboembolic stroke in mice. Neuroreport. 1998;9:2967–2970.
  • Kilic E, Hermann DM, Hossmann KA. Recombinant tissue-plasminogen activator-induced thrombolysis after cerebral thromboembolism in mice. Acta Neuropathol. 2000;99:219–222.
  • Hara T, Mies G, Hossmann KA. Effect of thrombolysis on the dynamics of infarct evolution after clot embolism of middle cerebral artery in mice. J Cereb Blood Flow Metab. 2000;20:1483–1491.
  • Brinker G, Pillekamp F, Hossmann KA. Brain hemorrhages after rt-PA treatment of embolic stroke in spontaneously hypertensive rats. Neuroreport. 1999;10:1943–1946.
  • Orset C, Macrez R, Young AR, et al. Mouse model of in situ thromboembolic stroke and reperfusion. Stroke. 2007;38:2771–2778.
  • Martinez de Lizarrondo S, Gakuba C, Herbig BA, et al. Potent thrombolytic effect of N-acetylcysteine on arterial thrombi. Circulation. 2017;136:646–660.
  • Hermann DM, Kleinschnitz C. Modeling vascular risk factors for the development of ischemic stroke therapies. Revised.
  • Mozaffarian D, Benjamin EJ, Go AS, et al.; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics - 2015 update: A report from the American Heart Association. Circulation. 2015;131:e29–e322.
  • Ay H, Koroshetz WJ, Vangel M, et al. Conversion of ischemic brain tissue into infarction increases with age. Stroke. 2002;36:2632–2636.
  • Lindner MD, Gribkoff VK, Donlan NA, et al. Long-lasting functional disabilities in middle-aged rats with small cerebral infarcts. J Neurosci. 2003;23:10913–10922.
  • Buchhold B, Mogoanta L, Suofu Y, et al. Environmental enrichment improves functional and neuropathological indices following stroke in young and aged rats. Restor Neurol Neurosci. 2007;25:467–484.
  • Calamante F, Thomas DL, Pell GS, et al. Measuring cerebral blood flow using magnetic resonance imaging techniques. J Cereb Blood Flow Metab. 1999;19:701–735.
  • Carter AR, Shulman GL, Corbetta M. Why use a connectivity-based approach to study stroke and recovery of function? Neuroimage. 2012;62:2271–2280.
  • Darsalia V, Heldmann U, Lindvall O, et al. Stroke-induced neurogenesis in aged brain. Stroke. 2005;36:1790–1795.
  • Popa-Wagner A, Stöcker K, Balseanu AT, et al. Effects of granulocyte-colony stimulating factor after stroke in aged rats. Stroke. 2010;41:1027–1031.
  • Popa-Wagner A, Dinca I, Yalikun S, et al. Accelerated delimitation of the infarct zone by capillary-derived nestin-positive cells in aged rats. Curr Neurovasc Res. 2006;3:3–13.
  • Markus TM, Tsai SY, Bollnow MR, et al. Recovery and brain reorganization after stroke in adult and aged rats. Ann Neurol. 2005;58:950–953.
  • Shen LH, Li Y, Chen J, et al. One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke. Stroke. 2007;38:2150–2156.
  • Zhang RL, Zhang Z, Zhang L, et al. Delayed treatment with sildenafil enhances neurogenesis and improves functional recovery in aged rats after focal cerebral ischemia. J Neurosci Res. 2006;83:1213–1219.
  • Gillani RL, Tsai SY, Wallace DG, et al. Cognitive recovery in the aged rat after stroke and anti-Nogo-A immunotherapy. Behav Brain Res. 2010;208:415–424.
  • Matter CM, Ma L, von Lukowicz T, et al. Increased balloon-induced inflammation, proliferation, and neointima formation in apolipoprotein E (ApoE) knockout mice. Stroke. 2006;37:2625–2632.
  • ElAli A, Doeppner TR, Zechariah A, et al. Increased blood-brain barrier permeability and brain edema after focal cerebral ischemia induced by hyperlipidemia: role of lipid peroxidation and calpain-1/2, matrix metalloproteinase-2/9, and RhoA overactivation. Stroke. 2011;42:3238–3244.
  • Plump AS, Smith JD, Hayek T, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992;71:343–353.
  • Herz J, Sabellek P, Lane TE, et al. Role of neutrophils in exacerbation of brain injury after focal cerebral ischemia in hyperlipidemic mice. Stroke. 2015;46:2916–2925.
  • Zechariah A, ElAli A, Hagemann N, et al. Hyperlipidemia attenuates vascular endothelial growth factor-induced angiogenesis, impairs cerebral blood flow, and disturbs stroke recovery via decreased pericyte coverage of brain endothelial cells. Arterioscler Thromb Vasc Biol. 2013;33:1561–1567.
  • Ishibashi S, Brown MS, Goldstein JL, et al. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J Clin Invest. 1993;92:883–893.
  • Purcell-Huynh DA, Farese RV Jr, Johnson DF, et al. Transgenic mice expressing high levels of human apolipoprotein B develop severe atherosclerotic lesions in response to a high-fat diet. J Clin Invest. 1995;95:2246–2257.
  • Kraft P, Schuhmann MK, Garz C, et al. Hypercholesterolemia induced cerebral small vessel disease. PLoS One. 2017;12:e0182822.
  • Süle Z, Mracskó E, Bereczki E, et al. Capillary injury in the ischemic brain of hyperlipidemic, apolipoprotein B-100 transgenic mice. Life Sci. 2009;84:935–939.
  • Gallou-Kabani C, Vigé A, Gross MS, et al. C57BL/6J and A/J mice fed a high-fat diet delineate components of metabolic syndrome. Obesity. 2007;15:1996–2005.
  • Okamoto K, Aoki K. Development of a strain of spontaneously hypertensive rats. Jpn Circ J. 1963;27:282–293.
  • Conrad CH, Brooks WW, Robinson KG. Bing OH Impaired myocardial function in spontaneously hypertensive rats with heart failure. Am J Physiol. 1991;260:H136–45.
  • Galaske RG, van Liew JB, Feld LG. Filtration and reabsorption of endogenous low-molecular-weight protein in the rat kidney. Kidney Int. 1979;16:394–403.
  • Komatsu K, Fröhlich ED, Ono H, et al. Glomerular dynamics and morphology of aged spontaneously hypertensive rats: effects of angiotensin-converting enzyme inhibition. Hypertension. 1995;25:207–213.
  • Lüscher TF, Aarhus LL. Vanhoutte PM Indomethacin improves the impaired endothelium-dependent relaxations in small mesenteric arteries of the spontaneously hypertensive rat. Am J Hypertens. 1990;3:55–58.
  • Campbell CA, Mackay KB, Patel S, et al. Effects of isradipine, an L-type calcium channel blocker on permanent and transient focal cerebral ischemia in spontaneously hypertensive rats. Exp Neurol. 1997;148:45–50.
  • Hennigan A, Callaghan CK, Kealy J, et al. Deficits in LTP and recognition memory in the genetically hypertensive rat are associated with decreased expression of neurotrophic factors and their receptors in the dentate gyrus. Behav Brain Res. 2009;197:371–377.
  • Liang AC, Mandeville ET, Maki T, et al. Effects of aging on neural stem/progenitor cells and oligodendrocyte precursor cells after focal cerebral ischemia in spontaneously hypertensive rats. Cell Transplant. 2016;25:705–714.
  • Kraft P, Schuhmann MK, Fluri F, et al. Efficacy and safety of platelet glycoprotein receptor blockade in aged and comorbid mice with acute experimental stroke. Stroke. 2015;46:3502–3506.
  • Rapp JP. Dahl salt-susceptible and salt-resistant rats. A review. Hypertension. 1982;4:753–763.
  • Deng Y, Rapp JP. Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats. Nat Genet. 1992;1:267–272.
  • Zhang JJ, Chao L, Chao J. Adenovirus-mediated kallikrein gene delivery reduces aortic thickening and stroke-induced death rate in Dahl salt-sensitive rats. Stroke. 1999;30:1925–1931.
  • Deodhar SD, Haas E, Goldblatt H. Production of antirenin to homologous renin and its effect of experimental renal hypertension. J Exp Med. 1964;119:425–432.
  • Zeng J, Zhang Y, Mo J, et al. Two-kidney, two-clip renovascular hypertensive rats can be used as stroke-prone rats. Stroke. 1998;29:1708–1713.
  • Ménard B, Chazalviel L, Roussel S, et al. Two-kidney one-clip is a pertinent approach to integrate arterial hypertension in animal models of stroke: serial magnetic resonance imaging studies of brain lesions before and during cerebral ischemia. J Cereb Blood Flow Metab. 2018;38:1769–1780.
  • Nedergaard M, Diemer NH. Focal ischemia of the rat brain, with special reference to the influence of plasma glucose concentration. Acta Neuropathol. 1987;73:131–137.
  • Chen J, Ye X, Yan T, et al. Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats. Stroke. 2011;42:3551–3558.
  • Yan T, Venkat P, Chopp M, et al. Neurorestorative responses to delayed human mesenchymal stromal cells treatment of stroke in type 2 diabetic rats. Stroke. 2016;47:2850–2858.
  • Khan MA, Schultz S, Othman A, et al. Hyperglycemia in stroke impairs polarization of monocytes/macrophages to a protective noninflammatory cell type. J Neurosci. 2016;36:9313–9325.
  • Rheni AK, Liu A, Perez-Pinzon MA, et al. Diabetic aggravation of stroke and animal models. Exp Neurol. 2017;292:63–79.
  • Kumari R, Willing LB, Patel SD, et al. Increased cerebral matrix metalloprotease-9 activity is associated with compromised recovery in the diabetic db/db mouse following a stroke. J Neurochem. 2011;119:1029–1040.
  • Mayanagi K, Katakam PV, Gáspár T, et al. Acute treatment with rosuvastatin protects insulin resistant (C57BL/6J ob/ob) mice against transient cerebral ischemia. J Cereb Blood Flow Metab. 2008;28:1927–1935.
  • Kumari R, Willing LB, Patel SD, et al. The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse. J Cereb Blood Flow Metab. 2010;30:352–360.
  • Nagaoka A, Iwatsuka H, Suzuoki Z, et al. Genetic predisposition to stroke in spontaneously hypertensive rats. Am J Physiol. 1976;230:1354–1359.
  • Rubattu S, Volpe M, Kreutz R, et al. Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease. Nat Genet. 1996;13:429–434.
  • Bailey EL, Smith C, Sudlow CL, et al. Is the spontaneously hypertensive stroke-prone rat a pertinent model of subcortical ischemic stroke? A systematic review. Int J Stroke. 2011;6:434–444.
  • Mies G, Hermann D, Ganten U, et al. Hemodynamics and metabolism in stroke-prone spontaneously hypertensive rats before manifestation of brain infarcts. J Cereb Blood Flow Metab. 1999;19:1238–1246.
  • Jalal FY, Yang Y, Thompson JF, et al. Hypoxia-induced neuroinflammatory white-matter injury reduced by minocycline in SHR/SP. J Cereb Blood Flow Metab. 2015;35:1145–1153.
  • Joutel A, Faraci FM. Cerebral small vessel disease: insights and opportunities from mouse models of collagen IV-related small vessel disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2014;45:1215–1221.
  • Gould DB, Phalan FC, Breedveld GJ, et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science. 2005;308:1167–1171.
  • Gould DB, Phalan FC, van Mil SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006;354:1489–1496.
  • Joutel A, Monet-Leprêtre M, Gosele C, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Invest. 2010;120:433–445.
  • Corbett D, Carmichael ST, Murphy TH, et al. Enhancing the alignment of the preclinical and clinical stroke recovery research pipeline: consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable Translational Working Group. Neurorehabil Neural Repair. 2017;31:699–707.

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