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Dear Colleagues,

Neuroinflammation is currently considered a hallmark of most neurological disorders, consisting of the collective dynamic response of glial cells to impaired nervous tissue homeostasis. The reactivities of astrocytes and

microglia are characterized by a wide spectrum of phenotypes that, in chronic diseases, may shift from neuroprotective to neurotoxic. It is known that the reactivity of glial cells is modulated by environmental conditions, including both the chemical and physical properties of the extracellular matrix, and

intense signaling reverberating among different cell types. According to an emerging idea, all cells in the nervous system are, indeed, connected by an intricate network of mutual influences and interdependencies, where intercellular interactions represent links and nodes. A deeper knowledge of the properties of this network, including the mechanisms that promote collective responses to different challenges, in both normal and pathological conditions, could help to understand some of the most controversial features of neuroinflammation.

This Special Issue fits this two-fold perspective; it is dedicated to research that can increase the current knowledge of cell interactions in neuroinflammation and their role in normal conditions. In addition, studies regarding how these interactions are affected by, or may affect, the extracellular matrix will also be considered for publication. This could inspire the concept of the nervous tissue as a microsystem, whose properties are affected by lifespan adaptations to a changing microenvironment.

Dr. Daniele Nosi
Dr. Jacopo Junio Valerio Branca
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30 pages, 40572 KiB

Open AccessArticle

Sex Dependent Disparities in the Central Innate Immune Response after Moderate Spinal Cord Contusion in Rat

by Mousumi Ghosh, Jinyoung Lee, Ashley N. Burke, Thomas A. Strong, Jacqueline Sagen and Damien D. Pearse

Cells 2024, 13(7), 645; https://doi.org/10.3390/cells13070645 - 06 Apr 2024

Viewed by 614

Abstract

Subacute spinal cord injury (SCI) displays a complex pathophysiology associated with pro-inflammation and ensuing tissue damage. Microglia, the resident innate immune cells of the CNS, in concert with infiltrating macrophages, are the primary contributors to SCI-induced inflammation. However, subpopulations of activated microglia can also possess immunomodulatory activities that are essential for tissue remodeling and repair, including the production of anti-inflammatory cytokines and growth factors that are vital for SCI recovery. Recently, reports have provided convincing evidence that sex-dependent differences exist in how microglia function during CNS pathologies and the extent to which these cells contribute to neurorepair and endogenous recovery. Herein we employed flow cytometry and immunohistochemical methods to characterize the phenotype and population dynamics of activated innate immune cells within the injured spinal cord of age-matched male and female rats within the first week (7 days) following thoracic SCI contusion. This assessment included the analysis of pro- and anti-inflammatory markers, as well as the expression of critical immunomodulatory kinases, including P38 MAPK, and transcription factors, such as NFκB, which play pivotal roles in injury-induced inflammation. We demonstrate that activated microglia from the injured spinal cord of female rats exhibited a significantly diminutive pro-inflammatory response, but enhanced anti-inflammatory activity compared to males. These changes included lower levels of iNOS and TLR4 expression but increased levels of ARG-1 and CD68 in females after SCI. The altered expression of these markers is indicative of a disparate secretome between the microglia of males and females after SCI and that the female microglia possesses higher phagocytic capabilities (increased CD68). The examination of immunoregulatory kinases and transcription factors revealed that female microglia had higher levels of phosphorylated P38^{Thr180/Tyr182} MAPK and nuclear NFκB pp50^Ser337 but lower amounts of nuclear NFκB pp65^Ser536, suggestive of an attenuated pro-inflammatory phenotype in females compared to males after SCI. Collectively, this work provides novel insight into some of the sex disparities that exist in the innate immune response after SCI and indicates that sex is an important variable when designing and testing new therapeutic interventions or interpretating positive or negative responses to an intervention. Full article

(This article belongs to the Special Issue Behind and beyond Neuroinflammation: State-of-Art and New Perspectives)

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