The ischemic environment drives microglia and macrophage function.
Stefano Fumagalli,Stefano Fumagalli,Carlo Perego,Francesca Pischiutta,Elisa R. Zanier,Maria Grazia De Simoni +5 more
TLDR
The selective responses of microglia and macrophages to hypoxia after stroke are discussed and relevant markers are reviewed with the aim of defining the different subpopulations of myeloid cells that are recruited to the injured site.Abstract:
Cells of myeloid origin, such as microglia and macrophages, act at the crossroads of several inflammatory mechanisms during pathophysiology. Besides pro-inflammatory activity (M1 polarization), myeloid cells acquire protective functions (M2) and participate in the neuroprotective innate mechanisms after brain injury. Experimental research is making considerable efforts to understand the rules that regulate the balance between toxic and protective brain innate immunity. Environmental changes affect microglia/macrophage functions. Hypoxia can affect myeloid cell distribution, activity, and phenotype. With their intrinsic differences, microglia and macrophages respond differently to hypoxia, the former depending on ATP to activate and the latter switching to anaerobic metabolism and adapting to hypoxia. Myeloid cell functions include homeostasis control, damage-sensing activity, chemotaxis, and phagocytosis, all distinctive features of these cells. Specific markers and morphologies enable to recognize each functional state. To ensure homeostasis and activate when needed, microglia/macrophage physiology is finely tuned. Microglia are controlled by several neuron-derived components, including contact-dependent inhibitory signals and soluble molecules. Changes in this control can cause chronic activation or priming with specific functional consequences. Strategies, such as stem cell treatment, may enhance microglia protective polarization. This review presents data from the literature that has greatly advanced our understanding of myeloid cell action in brain injury. We discuss the selective responses of microglia and macrophages to hypoxia after stroke and review relevant markers with the aim of defining the different subpopulations of myeloid cells that are recruited to the injured site. We also cover the functional consequences of chronically active microglia and review pivotal works on microglia regulation that offer new therapeutic possibilities for acute brain injury.read more
Citations
More filters
Journal ArticleDOI
Comparative Use of Contralateral and Sham-Operated Controls Reveals Traces of a Bilateral Genetic Response in the Rat Brain after Focal Stroke
Ivan B. Filippenkov,Julia A Remizova,Alina E. Denisova,Vasily V. Stavchansky,Ksenia D Golovina,Leonid V. Gubsky,Svetlana A. Limborska,Lyudmila V. Dergunova +7 more
TL;DR: It is believed that both sets of non-overlapping genes recorded transcriptome changes in IH cells associated with transhemispheric differences after focal cerebral ischemia, which should be considered when using the CH transcriptome as a control in studies of target brain regions in diseases that induce a global bilateral genetic response, such as stroke.
Journal ArticleDOI
Sickle cell disease mice have cerebral oxidative stress and vascular and white matter abnormalities.
Alfia Khaibullina,Luis E.F. Almeida,Sayuri Kamimura,Patricia M. Zerfas,Meghann L. Smith,Sebastian Vogel,Paul Wakim,Olavo M. Vasconcelos,Martha Quezado,Iren Horkayne-Szakaly,Zenaide M.N. Quezado +10 more
TL;DR: It is shown that SCD mice have increased levels of reactive oxygen species, protein carbonylation, and lipid peroxidation in hippocampus and cortex, thus suggesting increased cerebral oxidative stress, and this indicates that oxidative stress and stress-induced tissue damage is increased in susceptible brain regions, which may, in turn, contribute to neurocognitive deficits inSCD mice.
Dissertation
In vitro phenotypical and transcriptomic characterization of canine macrophages
TL;DR: Different morphologic and antigenic variances in DH82 cells depending on the passage number might in part explain the divergent reports on cell surface marker expression in the literature and comprehensively characterize the polarization properties of canine macrophages in vitro.
Journal ArticleDOI
Tackling Neuroinflammation After Traumatic Brain Injury: Complement Inhibition as a Therapy for Secondary Injury
Inge A van Erp,Iliana Michailidou,Thomas A. van Essen,Mathieu van der Jagt,Wouter A. Moojen,Wilco C. Peul,Frank Baas,Kees Fluiter +7 more
TL;DR: In this paper , the authors summarized the most important neuroinflammatory pathophysiology resulting from Traumatic Brain Injury (TBI) and the clinical trials performed to attenuate neuroinflammation, and presented the first clinical trial aimed at inhibition of complement activation in the early days after brain injury to reduce the risk of morbidity and mortality following severe TBI.
Journal ArticleDOI
X, but not Y, Chromosomal Complement Contributes to Stroke Sensitivity in Aged Animals.
Shaohua Qi,Conelius Ngwa,Abdullah Al Mamun,Sharmeen Romana,Ting Wu,Sean P. Marrelli,Arthur P. Arnold,Louise D. McCullough,Fu-zhong Liu +8 more
TL;DR: Mice with two copies of the X chromosome showed more robust microglial activation, higher brain-infiltrating leukocytes, elevated plasma cytokine levels, and enhanced co-localization of KDM6A and KDM5C with Iba1+ cells after stroke than mice with one X chromosome.
References
More filters
Journal ArticleDOI
Alternative activation of macrophages
TL;DR: The evidence in favour of alternative macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 is assessed, and its limits and relevance to a range of immune and inflammatory conditions are defined.
Journal ArticleDOI
The chemokine system in diverse forms of macrophage activation and polarization.
Alberto Mantovani,Alberto Mantovani,Antonio Sica,Silvano Sozzani,Silvano Sozzani,Paola Allavena,Annunciata Vecchi,Massimo Locati +7 more
TL;DR: Recent evidence suggests that differential modulation of the chemokine system integrates polarized macrophages in pathways of resistance to, or promotion of, microbial pathogens and tumors, or immunoregulation, tissue repair and remodeling.
Journal ArticleDOI
Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes
Alberto Mantovani,Silvano Sozzani,Silvano Sozzani,Massimo Locati,Paola Allavena,Antonio Sica +5 more
TL;DR: These functionally polarized cells, and similarly oriented or immature dendritic cells present in tumors, have a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression.
Journal ArticleDOI
Macrophage plasticity and polarization: in vivo veritas
Antonio Sica,Alberto Mantovani +1 more
TL;DR: The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for Macrophage-centered diagnostic and therapeutic strategies.
Journal ArticleDOI
Protective and pathogenic functions of macrophage subsets
Peter J. Murray,Thomas A. Wynn +1 more
TL;DR: The four stages of orderly inflammation mediated by macrophages are discussed: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis.