Abstract
It took decades to arrive at the general consensus dismissing the notion that the immune system is independent of the central nervous system. In the case of uncontrolled systemic inflammation, the relationship between the two systems is thrown off balance and results in cognitive and emotional impairment. It is specifically true for autoimmune pathologies where the central nervous system is affected as a result of systemic inflammation. Along with boosting circulating cytokine levels, systemic inflammation can lead to aberrant brain-resident immune cell activation, leakage of the blood–brain barrier, and the production of circulating antibodies that cross-react with brain antigens. One of the most disabling autoimmune pathologies known to have an effect on the central nervous system secondary to the systemic disease is systemic lupus erythematosus. Its neuropsychiatric expression has been extensively studied in lupus-like disease murine models that develop an autoimmunity-associated behavioral syndrome. These models are very useful for studying how the peripheral immune system and systemic inflammation can influence brain functions. In this review, we summarize the experimental data reported on murine models developing autoimmune diseases and systemic inflammation, and we explore the underlying mechanisms explaining how systemic inflammation can result in behavioral deficits, with a special focus on in vivo neuroimaging techniques.
Highlights
The effects of systemic inflammation on the central nervous system (CNS) are quite well illustrated in neuropsychiatric systemic lupus erythematosus (NPSLE), a poorly understood, severe form of systemic lupus erythematosus (SLE) disease that can affect up to 75% of SLE patients
After summarizing the main features of the pathology and the mouse models that recapitulate the human disease in terms of peripheral inflammation and behavioral deficiencies, we inquire into how advanced magnetic resonance imaging (MRI) techniques can be used non-invasively in mice to identify NPSLE symptoms and how this might translate to the human disease
In Murphy Roths Large (MRL)/lpr mice, these metabolic abnormalities were shown to reflect dysfunction of neuronal activity, but they did not correlate to structural changes that were detectable by MRI [66]
Summary
The effects of systemic inflammation on the central nervous system (CNS) are quite well illustrated in neuropsychiatric systemic lupus erythematosus (NPSLE), a poorly understood, severe form of systemic lupus erythematosus (SLE) disease that can affect up to 75% of SLE patients. This dramatic form of lupus disease covers a wide range of manifestations that are divided into focal and diffuse ones. The way in which neuroinflammation may cause central nervous symptoms in these murine lupus-prone models is explored
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