Brain inflammation is induced by co-morbidities and risk factors for stroke.
Authors
Drake, CBoutin, 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, Peter J
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
Affiliation
Faculty of Life Sciences, University of Manchester, Manchester, UK.Issue Date
2011-08
Metadata
Show full item recordAbstract
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.Citation
Brain inflammation is induced by co-morbidities and risk factors for stroke. 2011, 25 (6):1113-22 Brain Behav. Immun.Journal
Brain, Behavior, and ImmunityDOI
10.1016/j.bbi.2011.02.008PubMed ID
21356305Type
ArticleLanguage
enISSN
1090-2139ae974a485f413a2113503eed53cd6c53
10.1016/j.bbi.2011.02.008