Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

Dhungana, H. and Malm, T. and Dénes, Ádám (2013) Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection. AGING CELL, 12 (5). pp. 842-850. ISSN 1474-9718

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Abstract

Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of T. muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 hours. Aged, ischemic mice showed altered plasma and brain cytokine responses while the lesion size correlated with plasma pre-stroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and up-regulation of both plasma interleukin-17alpha and tumor necrosis factor alpha levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly. This article is protected by copyright. All rights reserved.

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