Neuroinflammation is the inflammatory response elicited by a variety of pathological conditions in the nervous system, including traumatic injury, neurodegenerative disorders, mental illness, infection, and toxin exposure. Depending on the etiology of the stressor, neuroinflammation encompasses a myriad of cellular responses, that range from the expression of inflammatory factors to the activation of the systemic immune system.
Neuroinflammatory signaling outcomes might be neuroprotective or neurodestructive, depending on the cell types involved, concurrent trophic and inflammatory signaling, and the nature of the disease stressor. Studies indicate that mechanisms and outcomes of pathological signaling are dependent upon the region of the nervous system, etiology of the stressor, and duration of the insult.
For example, a study by Zhao et al. determined that interleukin-1beta (IL-1ß) is associated with both acute and chronic inflammatory responses in the brain following systemic lipopolysaccharide (LPS)-induced endotoxemia. They determined that the acute IL-1ß response is independent of insult severity and coincident with diffuse upregulation of other neuroinflammatory factors, such as tumor necrosis factor alpha, interleukin-6 and MCP-1. In contrast, the chronic IL-1ß response is driven by activation of the Nod-like receptor protein 3 (NLRP3) inflammasome in a LPS dose-dependent manner that promotes degeneration of dopaminergic neurons in the substantia nigra.
While often associated with pathology, inflammatory pathways also perform constitutive and developmental functions in both the central (CNS) and peripheral (PNS) nervous system. In the healthy nervous system, neuroinflammatory factors, such as Interleukin-6 (IL-6) and CC-motif chemokines, behave much like trophic factors to promote cell survival, differentiation, and migration. As with pathological signaling, the mechanisms and outcomes of this constitutive signaling are also dependent on a variety of factors, including the region of the nervous system, developmental period, concurrent signaling, and cellular targets. For example, CNTF and LIF are members of the IL-6 family of cytokines. In the CNS, CNTF and LIF promote the differentiation of glia during development. In response to injury, CNTF can induce astrocyte reactivity, while LIF both promotes reactivity and is expressed by astrocytes as part of the reactivity response. In the PNS, CNTF is critical for the development of dorsal root ganglia (DRG) neurons, while both CNTF and LIF are important for DRG regeneration following injury.
Identifying the mechanisms underlying both constitutive and pathological neuroinflammatory pathways is critical for understanding the development and progression of neuropathological conditions hallmarked by neuroinflammation. The goal of this Research Topic is to provide an overview of current knowledge on the mechanisms of neuroinflammatory signaling in both healthy and diseased CNS and PNS. Studies that compare neuroinflammatory signaling in healthy and pathological conditions or delineate mechanisms that mediate the transition between healthy and pathological signaling are particularly relevant.
We welcome articles addressing, but not restricted to, the following:
• Upstream/downstream mechanisms and relevant pathways for neuroinflammatory factors in CNS or PNS pathological conditions
• Upstream/downstream mechanisms for neuroinflammatory factors in healthy CNS and PNS
• Underlying mechanisms of transition between healthy and pathological inflammatory signaling in the CNS and PNS
• Comparison of outcomes for neuroinflammatory pathways in healthy and diseased CNS
• Comparison of outcomes for neuroinflammatory pathways in healthy and diseased PNS
• Targeting strategies to prevent the induction of specific neuroinflammatory pathways in healthy and diseased CNS and PNS
• Novel methodologies linking specific neuroinflammatory pathways in healthy or diseased nervous system, and relative outcomes
