Thromboembolic Model of Cerebral Ischemia and Reperfusion in Mice
- 3k Downloads
Ischemic stroke is the fourth leading cause of death in the USA and a prominent cause of death globally. Besides thrombolytic therapy used in a small subset of patients, no alternative therapeutic strategy has been shown to improve the outcome of stroke patients. Preclinical models of ischemic stroke are an essential tool for investigating pathogenic processes that happen after the ischemic insult, as well as to screen for candidate therapeutic interventions. There are several models of rodent ischemic stroke including mechanical occlusion, thromboembolic stroke, and photothrombotic stroke. However, models that permit studying stroke in the context of thrombolytic therapy, such as thromboembolic models, are becoming of increasing interest to the research community. In this chapter, we describe a thromboembolic model of ischemic stroke with and without tissue-plasminogen activator-induced reperfusion. We describe protocols for microemboli preparation, surgical procedure, and post-stroke assessment of animals.
Key wordsCerebral ischemia reperfusion Stroke Thromboembolic stroke Microemboli Thrombolytic therapy Tissue-plasminogen activator
This work is funded by a Department of Veterans Affairs Merit Award (RX00114) and the NIH (P20GM109040) to S.T. and an American Heart Association Pre-doctoral Fellowship Award (15PRE25250009) to A.A.
- 1.Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou M, Vollset SE, Ozgoren AA, Abdalla S, Abd-Allah F (2015) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385:117–171CrossRefGoogle Scholar
- 2.Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER III, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB, American Heart Association Statistics C, Stroke Statistics S (2015) Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131:29–322Google Scholar
- 3.Wardlaw JM, Koumellis P, Liu M (2013) Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke. Cochrane Database System Rev 5, CD000514Google Scholar
- 4.Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kummer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA, Interventional Management of Stroke IIII (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 368:893–903CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S, Investigators AT, Investigators ET, Investigators Nr-PSG (2004) Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 363:768–774CrossRefPubMedGoogle Scholar
- 16.Albers GW, Goldstein LB, Hess DC, Wechsler LR, Furie KL, Gorelick PB, Hurn P, Liebeskind DS, Nogueira RG, Saver JL (2011) Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies. Stroke 42:2645–2650CrossRefPubMedGoogle Scholar
- 19.Jiang Q, Zhang RL, Zhang ZG, Ewing JR, Divine GW, Chopp M (1998) Diffusion-, T2-, and perfusion-weighted nuclear magnetic resonance imaging of middle cerebral artery embolic stroke and recombinant tissue plasminogen activator intervention in the rat. J Cereb Blood Flow Metab 18:758–767CrossRefPubMedGoogle Scholar
- 25.Tennant KA, Asay AL, Allred RP, Ozburn AR, Kleim JA, Jones TA (2010) The vermicelli and capellini handling tests: simple quantitative measures of dexterous forepaw function in rats and mice. J Vis Exp (41):pii: 2076Google Scholar
- 26.Rosenfeld CS, Ferguson SA (2014) Barnes maze testing strategies with small and large rodent models. J Vis Exp (84):e51194Google Scholar
- 28.Bromley-Brits K, Deng Y, Song W (2011) Morris water maze test for learning and memory deficits in Alzheimer’s disease model mice. J Vis Exp (53):pii: 2920Google Scholar