Neuroinflammation: Integrated Nervous Tissue Response through Intercellular Interactions at the “Whole System” Scale

Abstract

Different cell populations in the nervous tissue establish numerous, heterotypic interactions and perform specific, frequently intersecting activities devoted to the maintenance of homeostasis. Microglia and astrocytes, respectively the immune and the “housekeeper” cells of nervous tissue, play a key role in neurodegenerative diseases. Alterations of tissue homeostasis trigger neuroinflammation, a collective dynamic response of glial cells. Reactive astrocytes and microglia express various functional phenotypes, ranging from anti-inflammatory to pro-inflammatory. Chronic neuroinflammation is characterized by a gradual shift of astroglial and microglial phenotypes from anti-inflammatory to pro-inflammatory, switching their activities from cytoprotective to cytotoxic. In this scenario, the different cell populations reciprocally modulate their phenotypes through intense, reverberating signaling. Current evidence suggests that heterotypic interactions are links in an intricate network of mutual influences and interdependencies connecting all cell types in the nervous system. In this view, activation, modulation, as well as outcomes of neuroinflammation, should be ascribed to the nervous tissue as a whole. While the need remains of identifying further links in this network, a step back to rethink our view of neuroinflammation in the light of the “whole system” scale, could help us to understand some of its most controversial and puzzling features.

Biological aging processes underlying cognitive decline and neurodegenerative disease

“…Thus, it is possible that mild neuronal inflammation may provide some early protection. On the other hand, as disease etiology progresses, an association with neuroinflammatory markers, including C-reactive protein (CRP), triggering receptor expressed on myeloid cells 2 (TREM2), intercellular adhesion molecule 1 (ICAM1), IFNs, and the IL-1 family, is typically reported ( 157 – 160 ).…”

Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

“…Under pathophysiological conditions, activated microglia may differentiate into a continuum of states between phenotypically polarized M1 and M2 states. M1 microglia, whose polarization prevails in neurodegenerative diseases, exert neurotoxic effects and produce pro-inflammatory cytokines and chemokines that maintain inflammatory processes, whereas M2 microglia are neuroprotective, produce anti-inflammatory cytokines and terminate inflammation, contributing to tissue repair [58,59]. The most important pro-inflammatory and cytotoxic mediators produced by M1 microglial cells are cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-1 and IL-6, and inhibition of their production may be an important factor for reducing neuronal damage.…”

VRT-043198 Ameliorates Surgery-Induced Neurocognitive Disorders by Restoring the NGF and BNDF Expression in Aged Mice

“…Previous studies reported that chronic inflammatory response induced astrocytic and microglial activation in the hippocampus. 31 , 32 In this study, it was found that abdominal exploratory laparotomy led to a significant increase in the intensity of GFAP (vs sham, P <0.0001; Figure 4A and B ) and Iba1 (vs sham, P <0.0001; Figure 4D and E ), while VRT-043198 administration partially reversed these changes (vs AEL, P <0.0001 for GFAP; vs AEL, P =0.0002 for Iba1; Figure 4A, B, D and E ). In the present study, A1-type astrocytes indicated by C3 complement 33 and M1-type microglia indicated by CD86 34 were selected as biomarkers of inflammatory response in the late post-surgical stage.…”