• Open Access

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

Authors

  • Hiramani Dhungana,

    1. Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Tarja Malm,

    Corresponding author
    • Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Adam Denes,

    1. Faculty of Life Sciences, University of Manchester, Manchester, UK
    2. Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, Hungary
    Search for more papers by this author
  • Piia Valonen,

    1. Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
    Search for more papers by this author
  • Sara Wojciechowski,

    1. Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
    Search for more papers by this author
  • Johanna Magga,

    1. Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
    Search for more papers by this author
  • Ekaterina Savchenko,

    1. Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
    Search for more papers by this author
  • Neil Humphreys,

    1. Faculty of Life Sciences, University of Manchester, Manchester, UK
    Search for more papers by this author
  • Richard Grencis,

    1. Faculty of Life Sciences, University of Manchester, Manchester, UK
    Search for more papers by this author
  • Nancy Rothwell,

    1. Faculty of Life Sciences, University of Manchester, Manchester, UK
    Search for more papers by this author
  • Jari Koistinaho

    1. Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
    2. Department of Oncology, Kuopio University Hospital, Kuopio, Finland
    Search for more papers by this author

Correspondence

Tarja Malm, PhD, A.I.Virtanen Institute for Molecular Science, University of Kuopio, PO Box 1627, FI-70211, Kuopio, Finland. Tel.: +358 40 3552209; fax: +358 17 16 3030; e-mail: tarja.malm@uef.fi

Summary

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 Trichuris 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 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α 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.

Ancillary