Middle Cerebral Artery Occlusion in Aged Animal Model

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.