期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 91, 期 -, 页码 487-497出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2020.10.025
关键词
Inflammation; Depression; BBB permeability; CSF; Choroid plexus; PET; Tracer percolation
资金
- Cambridgeshire and Peterborough NHS Foundation Trust
- University of Cambridge
- Wellcome Trust [104025]
- Janssen
- GlaxoSmithKline
- Lundbeck
- Pfizer
- National Institute of Health Research (NIHR) Clinical Research Network: Kent, Surrey and Sussex Eastern
- National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust
- King's College London
- NIHR Cambridge Biomedical Research Centre (Mental Health)
- NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust
- Janssen Pharmaceutical Companies of JohnsonJohnson
- MRC [MC_G0802534, G0900891, G108/603, MR/N029488/1] Funding Source: UKRI
The studies suggest that peripheral inflammation may lead to a reduction in blood-brain barrier permeability, disrupting brain homeostasis and inducing depressive symptoms.
The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood-brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity. To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts (N = 51 patients and N = 25 controls) and a second study where peripheral inflammation in N = 7 healthy controls was induced via subcutaneous injection of interferon (IFN)-alpha. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radio tracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100 beta, that was unchanged. These results suggest a different model of peripheral-to-central immunity interaction whereas peripheral inflammation may cause a reduction in BBB permeability. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms.
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