Abstract
Stroke is a devastating brain injury resulting in high mortality and substantial loss of function, affecting >15 million people worldwide annually; the majority of which are over 65 years old (Feigin et al., Lancet 383:245–254, 2014; Feigin et al., Lancet Neurol 2:43–53, 2003; Benjamin et al., Circulation 135:e146–e603, 2017; Writing Group et al., Circulation 133:447–454, 2016; Roy-O’Reilly, McCullough, Endocrinology 159:3120–3131, 2018). Aging is a significant risk factor for stroke, and older patients have higher mortality and poorer functional recovery after stroke compared with younger patients (Arboix et al., J Am Geriatr Soc 48:36–41, 2000; Rojas et al., Eur J Neurol 14:895–899, 2007). Despite the importance of aging in the pathophysiology of stroke, the vast majority of preclinical studies have only used young animals. Understanding the mechanisms underlying stroke-induced brain damage and post-stroke functional recovery in aged animals is an urgent need. This step is essential to the development of therapeutics for treating stroke patients, most of whom are elderly. To understand the pathophysiology of ischemic injury induced by middle cerebral artery occlusion (MCAO), one of the most common type of stroke seen clinically (Writing Group et al., Circulation 133:e38–360, 2016), it is imperative to include older animals in preclinical testing. The purpose of this chapter is to provide insight on successfully reproducing MCAO injury in translationally relevant aged animals.
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References
Alvarez-Rodriguez L, Lopez-Hoyos M, Munoz-Cacho P et al (2012) Aging is associated with circulating cytokine dysregulation. Cell Immunol 273:124–132
Arboix A, Garcia-Eroles L, Massons J et al (2000) Acute stroke in very old people: clinical features and predictors of in-hospital mortality. J Am Geriatr Soc 48:36–41
Benjamin EJ, Blaha MJ, Chiuve SE et al (2017) Heart disease and stroke Statistics-2017 update: a report from the American Heart Association. Circulation 135:e146–e603
Bogousslavsky J, Van Melle G, Regli F (1988) The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke 19:1083–1092
Carmichael ST (2005) Rodent models of focal stroke: size, mechanism, and purpose. NeuroRx 2:396–409
Chesnokova V, Pechnick RN, Wawrowsky K (2016) Chronic peripheral inflammation, hippocampal neurogenesis, and behavior. Brain Behav Immun 58:1–8
Feigin VL, Forouzanfar MH, Krishnamurthi R et al (2014) Global and regional burden of stroke during 1990-2010: findings from the global burden of disease study 2010. Lancet 383:245–254
Feigin VL, Lawes CM, Bennett DA et al (2003) Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol 2:43–53
Fluri F, Schuhmann MK, Kleinschnitz C (2015) Animal models of ischemic stroke and their application in clinical research. Drug Des Devel Ther 9:3445–3454
Franceschi C, Capri M, Monti D et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105
Guzik A, Bushnell C (2017) Stroke epidemiology and risk factor management. Continuum 23:15–39
Hossmann KA (2006) Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol 26:1057–1083
Koizumi JN, Nakazawa T, Ooneda G (1986) A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke 8:1–8
Longa EZ, Weinstein PR, Carlson S et al (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91
Manwani B, Friedler B, Verma R et al (2014) Perfusion of ischemic brain in young and aged animals: a laser speckle flowmetry study. Stroke 45:571–578
Manwani B, Liu F, Xu Y et al (2011) Functional recovery in aging mice after experimental stroke. Brain Behav Immun 25:1689–1700
Meyers DG, Bendon KA, Hankins JH et al (1990) The effect of baseline electrocardiographic abnormalities on the diagnostic accuracy of exercise-induced ST segment changes. Am Heart J 119:272–276
Reeves MJ, Bushnell CD, Howard G et al (2008) Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. Lancet Neurol 7:915–926
Rojas JI, Zurru MC, Romano M et al (2007) Acute ischemic stroke and transient ischemic attack in the very old–risk factor profile and stroke subtype between patients older than 80 years and patients aged less than 80 years. Eur J Neurol 14:895–899
Roy-O’reilly M, Mccullough LD (2018) Age and sex are critical factors in ischemic stroke pathology. Endocrinology 159:3120–3131
Shahjouei S, Cai PY, Ansari S et al (2016) Middle cerebral artery occlusion model of stroke in rodents: a step-by-step approach. J Vasc Interv Neurol 8:1–8
Thor AD (1992) Prognostic factors in breast cancer: integrating the cytology laboratory. Diagn Cytopathol 8:319–321
Writing Group M, Mozaffarian D, Benjamin EJ et al (2016) Executive summary: heart disease and stroke statistics–2016 update: a report from the American Heart Association. Circulation 133:447–454
Writing Group M, Mozaffarian D, Benjamin EJ et al (2016) Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133:e38–e360
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Goodman, G.W., Nguyen, J.N., Blixt, F.W., Maniskas, M.E., McCullough, L.D., Chauhan, A. (2023). Middle Cerebral Artery Occlusion in Aged Animal Model. In: Karamyan, V.T., Stowe, A.M. (eds) Neural Repair. Methods in Molecular Biology, vol 2616. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2926-0_32
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DOI: https://doi.org/10.1007/978-1-0716-2926-0_32
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