Biomarkers of Neuroinflammation Proceedings of a Workshop (2018) / Chapter Skim
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2 Biomarkers of Neuroinflammation: Challenges and Potential Opportunities
2 Biomarkers of Neuroinflammation: Challenges and Potential Opportunities
Pages 5-14
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From page 5... ...
; disorders induced by brain injury; and neuropsychiatric disorders, such as depression and schizophrenia. Brian Campbell said that similar cell types and inflammatory mediators are induced across the range of these disorders, yet the consequences vary from toxic processes, such as the release of proinflammatory cytokines or reactive oxygen species, to reparative processes, such as the release of anti-inflammatory cytokines or stimulation of neuroprotective and angiogenic factors.
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From page 6... ...
The complexity of neuroinflammation is exacerbated by substantial biological heterogeneity across individuals and over the disease course, including differences in the subsets of immune cells activated, said Campbell. Heterogeneity is seen not only in the types of cells but in their spatial and temporal appearance and functional activity states during development in healthy individuals as well as in normal aging and disease, added Linda Brady.
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From page 7... ...
An audience participant noted that because neuroinflammation can produce both damaging and compensatory effects, it is critical to understand both the normal trajectory of pro- and anti-inflammatory molecules and signaling mechanisms as well as the extent to which activation of microglia and other immune cells represents a compensatory mechanism in a disease process. Miller suggested that researchers investigate under what conditions increased expression of these molecules reflect neuroinflammation versus normal physiological processes, such as synaptic plasticity.
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From page 8... ...
However, they do show other pathological features, including axonal transport issues, the presence of amyloid precursor protein, myelin loss, astrogliosis, and inflammation microgliosis, and they also show behavioral manifestations, such as decline in memory performance. OVERVIEW OF POTENTIAL OPPORTUNITIES Developing Static and Dynamic Biomarkers in Parallel In the context of therapeutic development, biomarkers are needed for multiple purposes: to diagnose disease, monitor therapy, and demonstrate target engagement in clinical trials.
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From page 9... ...
Intermediate biomarkers, such as those obtained from "omics" studies applied to easily accessible samples, can help generate hypotheses that guide dynamic biomarker development, he said. Bullmore suggested that in clinical trials for anti-inflammatory drugs in non-psychiatric disorders, much earlier end point measurements of brain function and mental state changes should be adopted.
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From page 10... ...
An audience participant added that peripheral biomarkers could provide better understanding of the dialogue between the brain and the immune system, for example, how exercise and environmental enrichment may impact depression. Developing Novel Biomarkers of Neuroinflammation While many neuroinflammatory mediators have been identified and are being developed as potential biomarkers, additional novel markers are emerging as understanding of the complex mechanisms involved becomes more refined.
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From page 11... ...
. New Strategies for Biomarker Development Given the complex mechanisms of neuroinflammation and its involvement in both healthy and disease states, many workshop participants stated that new strategies are needed to collect and analyze relevant data for biomarker development.
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From page 12... ...
, suggested that lymphocyte profiling might also represent a useful biomarker because the adaptive immune system has been shown to affect mood and, in animals, to improve hippocampal neurogenesis, which may be relevant in depression. • Although several workshop participants spoke about the limited funding currently available for research on neuroinflammatory diseases, one audience participant commented that funding is available through the Department of Defense for Gulf War illness research, including research related to TBI.
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From page 13... ...
He said that although tissue from the hippocampus is limited because of its small size in humans, tissue from other brain areas is more readily available. • Because subject recruitment presents a major challenge to evaluating PET ligands in depression and AD, Robert Innis, chief of the Molecular Imaging Branch at NIMH, offered to work with investigators in this area by providing free PET scans at NIMH facilities to patients in whom plasma and CSF biomarkers have been assessed.
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