The incidence of cerebrovascular disease is highest in the elderly population. However, the pathophysiological mechanisms of brain response to cerebral ischemia in old age are currently poorly understood. Ischemic changes in the commonly used young animal stroke models do not reflect the molecular changes associated with the aged brain. Neuroinflammation and oxidative stress are important pathogenic processes occurring during the acute phase of cerebral ischemia. Free radical generation is also implicated in the aging process, and the combination of these effects in elderly stroke patients could explain the higher risk of morbidity and mortality. A better understanding of stroke pathophysiology in the elderly patient would assist in the development of new therapeutic strategies for this vulnerable age group. With the increasing use of reperfusion therapies, inflammatory pathways and oxidative stress remain attractive therapeutic targets for the development of adjuvant neuroprotective agents. This paper will discuss these molecular aspects of acute stroke and senescence from a bench-to-bedside research perspective. 1. Introduction Old age is an important risk factor for stroke and is associated with increased patient morbidity and mortality [1, 2]. Many of these patients have associated comorbidities, for example, cardiovascular and respiratory disease. This is further complicated by an increased risk of cognitive and functional decline in elderly stroke patients [3, 4]. Poor functional recovery has also been demonstrated in aged-animal models [5]. The pathophysiological mechanisms of the brains response to an ischemic insult in old age are poorly understood. Most preclinical stroke studies have been performed in young animal models and therefore do not reflect the molecular changes associated with the aged brain [6, 7]. This has been one of the criticisms of preclinical stroke neuroprotection studies and implicated in the resulting failure of clinical stroke neuroprotection trials [8, 9]. Neuroprotective therapies targeting NMDA and AMPA receptors have demonstrated reduced efficacy in aged-animal stroke models [10]. The pharmacokinetic and pharmacodynamic properties of neuroprotective agents may also be different in older patients [8]. This therefore emphasizes the importance of assessing potential neuroprotective therapies in preclinical aged animal stroke models and early clinical studies of elderly patients [6]. A better understanding of stroke pathogenesis in the aged brain would assist in the development of new therapeutic strategies for treatment
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