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Brain inflammation is induced by co-morbidities and risk factors for stroke Open Access


Author or creator
Drake, Caroline
Boutin, Hervé
Jones, Matthew S.
Denes, Adam
McColl, Barry W.
Selvarajah, Johann R.
Hulme, Sharon
Georgiou, Rachel F.
Hinz, Rainer
Gerhard, Alexander
Vail, Andy
Prenant, Christian
Julyan, Peter
Maroy, Renaud
Brown, Gavin
Smigova, Alison
Herholz, Karl
Kassiou, Michael
Crossman, David
Francis, Sheila
Proctor, Spencer D.
Russell, James C.
Hopkins, Stephen J.
Tyrrell, Pippa J.
Rothwell, Nancy J.
Allan, Stuart M.
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Chronic systemic inflammatory conditions, such as atherosclerosis, diabetes and obesity are associated with increased risk of stroke, which suggests that systemic inflammation may contribute to the development of stroke in humans. The hypothesis that systemic inflammation may induce brain pathology can be tested in animals, and this was the key objective of the present study. First, we assessed inflammatory changes in the brain in rodent models of chronic, systemic inflammation. PET imaging revealed increased microglia activation in the brain of JCR-LA (corpulent) rats, which develop atherosclerosis and obesity, compared to the control lean strain. Immunostaining against Iba1 confirmed reactive microgliosis in these animals. An atherogenic diet in apolipoprotein E knock-out (ApoE−/−) mice induced microglial activation in the brain parenchyma within 8 weeks and increased expression of vascular adhesion molecules. Focal lipid deposition and neuroinflammation in periventricular and cortical areas and profound recruitment of activated myeloid phagocytes, T cells and granulocytes into the choroid plexus were also observed. In a small, preliminary study, patients at risk of stroke (multiple risk factors for stroke, with chronically elevated C-reactive protein, but negative MRI for brain pathology) exhibited increased inflammation in the brain, as indicated by PET imaging. These findings show that brain inflammation occurs in animals, and tentatively in humans, harbouring risk factors for stroke associated with elevated systemic inflammation. Thus a “primed” inflammatory environment in the brain may exist in individuals at risk of stroke and this can be adequately recapitulated in appropriate co-morbid animal models.
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Drake, C., Boutin, H., Jones, M. S., Denes, A., McColl, B. W., Selvarajah, J. R., Hulme, S., Georgiou, R. F., Hinz, R., Gerhard, A., Vail, A., Prenant, C., Julyan, P., Maroy, R., Brown, G., Smigova, A., Herholz, K., Kassiou, M., Crossman, D., Francis, S., Proctor, S. D., Russell, J. C., Hopkins, S. J., Tyrrell, P. J., Rothwell, N. J., & Allan, S. M. (2011). Brain inflammation is induced by co-morbidities and risk factors for stroke. Brain, Behavior, and Immunity, 25(6), 1113-1122.


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