Neuroscience
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Review
Imaging of inflammation in the peripheral and central nervous system by magnetic resonance imaging.
Inflammation plays a central role in the pathophysiology of numerous disorders of the nervous system, but is also pivotal for repair processes like peripheral nerve regeneration. In this review we summarize recent advances in cellular magnetic resonance imaging (MRI) while nuclear imaging methods to visualize neuroinflammation are covered by Wunder et al. [Wunder A, Klohs J, Dirnagl U (2009) Non-invasive imaging of central nervous system inflammation with nuclear and optical imaging. Neuroscience, in press]. ⋯ Iron oxide-contrast-enhanced MRI allowed in vivo visualization of cellular inflammation during wallerian degeneration, experimental autoimmune neuritis and encephalomyelitis, and stroke in rodents, but also in patients with multiple sclerosis and stroke. Importantly, cellular MRI provides additional information to gadolinium-DTPA-enhanced MRI since cellular infiltration and breakdown of the blood-brain barrier are not closely linked. Coupling of antibodies to iron oxide particles opens new avenues for molecular MRI and has been successfully used to visualize cell adhesion molecules guiding inflammation.
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We have all at some time experienced the non-specific symptoms that arise from being ill following a systemic infection. These symptoms, such as fever, malaise, lethargy and loss of appetite are often referred to as "sickness behavior" and are a consequence of systemically produced pro-inflammatory mediators. These inflammatory mediators signal to the brain, leading to activation of microglial cells, which in turn, signal to neurons to induce adaptive metabolic and behavioral changes. ⋯ However, in animals and patients with chronic neurodegenerative disease, multiple sclerosis, stroke and even during normal aging, systemic inflammation leads to inflammatory responses in the brain, an exaggeration of clinical symptoms and increased neuronal death. These observations imply that, as the population ages and the number of individuals with CNS disorders increases, relatively common systemic infections and inflammation will become significant risk factors for disease onset or progression. In this review we discuss the underlying mechanisms responsible for sickness behavior induced by systemic inflammation in the healthy brain and how they might be different in individuals with CNS pathology.
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Neurodegeneration and signs of immune activation, with T cell infiltration, major histocompatibility complex class II expression and glial activation, occur in many neurological diseases. Although particular qualities of the inflammatory response have been proposed to be of importance, still very little is known about the exact factors that determine susceptibility to neurodegeneration. Mechanistic studies have yielded conflicting results, where inflammation is suggested both to attenuate and aggravate loss of nerve cells depending on the circumstances. ⋯ We here review emerging evidence using this approach that indicates different pathways related both to adaptive and local innate immune responses, which determine strain-specific susceptibility to neuroimmune inflammation and neurodegeneration. Exact positioning of genes in these types of complex traits will be important for the understanding of pathogenetic mechanisms and to direct the focus of functional studies using classical experimental tools. Ultimately, a better knowledge about the interplay between the nervous system and the local and systemic immune system can define new ways of intervention in neurodegenerative processes.
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Following injury to the nervous system, the activation of macrophages, microglia, and T-cells profoundly affects the ability of neurons to survive and to regenerate damaged axons. The primary visual pathway provides a well-defined model system for investigating the interactions between the immune system and the nervous system after neural injury. ⋯ T cells modulate this response, whereas microglia are thought to contribute to the loss of retinal ganglion cells in this model and in certain ocular diseases. This review discusses the complex and sometimes paradoxical actions of blood-borne macrophages, resident microglia, and T-cells in determining the outcome of injury in the primary visual pathway.