Death receptors on reactive astrocytes

Neurology ◽  
2003 ◽  
Vol 60 (4) ◽  
pp. 548-554 ◽  
Author(s):  
Pierre-Yves Dietrich ◽  
Paul R. Walker ◽  
Philippe Saas
Keyword(s):  
Brain Injury ◽  
Immune Responses ◽  
Death Receptors ◽  
Reactive Astrocytes ◽  
Brain Inflammation ◽  
Fine Tuning ◽  
Immune Mediated ◽  
Anti Inflammatory ◽  
The Brain

Immune responses protect the CNS against pathogens. However, the fact that there is little dispensable tissue in the brain makes regulation necessary to avoid disastrous immune-mediated damage. Astrocytes respond vigorously to any brain injury (e.g., tumor, stroke, AD, MS, HIV) and are postulated to play an important role in the fine tuning of brain inflammation. The authors propose that astrocytes use death receptors to modulate pro- and anti-inflammatory effects.

scholarly journals Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage

2021 ◽  
Vol 6 (56) ◽  
pp. eabd6279
Author(s):  
Michael H. Askenase ◽  
Brittany A. Goods ◽  
Hannah E. Beatty ◽  
Arthur F. Steinschneider ◽  
Sofia E. Velazquez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Injury ◽  
Immune Responses ◽  
Intracerebral Hemorrhage ◽  
Human Brain ◽  
Inflammatory Factors ◽  
Lipid Mediator ◽  
Prostaglandin E ◽  
Anti Inflammatory ◽  
Over Time

Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14+ monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort. Initially, hematoma myeloid cells expressed a robust anabolic proinflammatory profile characterized by activation of hypoxia-inducible factors (HIFs) and expression of genes encoding immune factors and glycolysis. Subsequently, inflammatory gene expression decreased over time, whereas anti-inflammatory circuits were maintained and phagocytic and antioxidative pathways up-regulated. During this transition to immune resolution, glycolysis gene expression and levels of the potent proresolution lipid mediator prostaglandin E2 remained elevated in the hematoma, and unexpectedly, these elevations correlated with positive patient outcomes. Ex vivo activation of human macrophages by ICH-associated stimuli highlighted an important role for HIFs in production of both inflammatory and anti-inflammatory factors, including PGE2, which, in turn, augmented VEGF production. Our findings define the time course of myeloid activation in the human brain after ICH, revealing a conserved progression of immune responses from proinflammatory to proresolution states in humans after brain injury and identifying transcriptional programs associated with neurological recovery.

scholarly journals “Corneal Nerves, CD11c+ Dendritic Cells and Their Impact on Ocular Immune Privilege”

2021 ◽  
Vol 12 ◽  
Author(s):  
Jerry Y. Niederkorn
Keyword(s):  
Immune Responses ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Immune Privilege ◽  
Innate Immune Responses ◽  
Regulatory Processes ◽  
Immune Mediated ◽  
Corneal Nerves ◽  
The Central Nervous System ◽  
The Brain

The eye and the brain have limited capacities for regeneration and as such, immune-mediated inflammation can produce devastating consequences in the form of neurodegenerative diseases of the central nervous system or blindness as a result of ocular inflammatory diseases such as uveitis. Accordingly, both the eye and the brain are designed to limit immune responses and inflammation – a condition known as “immune privilege”. Immune privilege is sustained by physiological, anatomical, and regulatory processes that conspire to restrict both adaptive and innate immune responses.

scholarly journals Systemic inflammation in hemorrhagic strokes – A novel neurological sign and therapeutic target?

2019 ◽  
Vol 39 (6) ◽  
pp. 959-988 ◽  
Author(s):  
Aisha R Saand ◽  
Fang Yu ◽  
Jun Chen ◽  
Sherry H-Y Chou
Keyword(s):  
Brain Injury ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Systemic Inflammation ◽  
Systemic Disease ◽  
Systemic Inflammatory Response ◽  
Organ Systems ◽  
Novel Therapeutic Strategies ◽  
The Impact ◽  
The Brain

Growing evidences suggest that stroke is a systemic disease affecting many organ systems beyond the brain. Stroke-related systemic inflammatory response and immune dysregulations may play an important role in brain injury, recovery, and stroke outcome. The two main phenomena in stroke-related peripheral immune dysregulations are systemic inflammation and post-stroke immunosuppression. There is emerging evidence suggesting that the spleen contracts following ischemic stroke, activates peripheral immune response and this may further potentiate brain injury. Whether similar brain–immune crosstalk occurs in hemorrhagic strokes such as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is not established. In this review, we systematically examined animal and human evidence to date on peripheral immune responses associated with hemorrhagic strokes. Specifically, we reviewed the impact of clinical systemic inflammatory response syndrome (SIRS), inflammation- and immune-associated biomarkers, the brain–spleen interaction, and cellular mediators of peripheral immune responses to ICH and SAH including regulatory T cells (Tregs). While there is growing data suggesting that peripheral immune dysregulation following hemorrhagic strokes may be important in brain injury pathogenesis and outcome, details of this brain-immune system cross-talk remain insufficiently understood. This is an important unmet scientific need that may lead to novel therapeutic strategies in this highly morbid condition.

Carrageenan-induced brain inflammation

1986 ◽  
Vol 65 (5) ◽  
pp. 679-685 ◽  
Author(s):  
Daniel A. Gamache ◽  
John T. Povlishock ◽  
Earl F. Ellis
Keyword(s):  
Arachidonic Acid ◽  
Vascular Permeability ◽  
Brain Inflammation ◽  
Intraventricular Injection ◽  
Arachidonic Acid Metabolite ◽  
Maximum Increase ◽  
Peripheral Tissues ◽  
Neutrophil Extravasation ◽  
Anti Inflammatory ◽  
The Brain

✓ Administration of the mucopolysaccharide, carrageenan (CAR), into the hind paw of the rat or mouse induces a local inflammation characterized by increased arachidonic acid metabolism, increased vascular permeability, edema, and neutrophil extravasation. Carrageenan-induced hind-paw inflammation is inhibited by prostaglandin synthesis inhibitors, and this assay predicts the clinical success of anti-inflammatory agents in reducing peripheral inflammation. The purpose of this study was to determine if intraventricular injection of CAR would induce brain inflammation similar to that evoked by CAR in peripheral tissues. The present study demonstrates that CAR injection into the ventricles of the mouse brain does in fact induce an inflammatory response very similar to that caused by injection of CAR into the peripheral tissues. The brain response to CAR was dose-dependent, with the maximum increase in cerebrovascular permeability to iodine-125-labeled human serum albumin and percent brain water occurring after injection of 50 µg CAR. As is seen in CAR-induced inflammation of the hind paw, the maximum increase in brain vascular permeability occurred 4 hours after CAR injection. Histological analysis of brains 4 hours after CAR administration showed global neutrophil extravasation into the subarachnoid space and evidence of focal neuronal swelling. Methotrexate-induced neutropenia, however, failed to diminish the permeability response to CAR. Gas chromatographic and mass spectrometric measurements of brain prostaglandins 4 hours after CAR injection revealed a significantly increased level of 6-keto-prostaglandin F1α. These results indicate that a significant increase in prostacyclin, the pro-inflammatory arachidonic acid metabolite, during CAR-induced brain inflammation is likely. These studies suggest that CAR-induced brain inflammation may be a useful model on which to test the efficacy of anti-inflammatory agents in the brain, as well as providing information concerning the mediators and mechanisms by which the brain may sustain inflammatory injury.

scholarly journals A Programmed Anti‐Inflammatory Nanoscaffold (PAIN) as a 3D Tool to Understand the Brain Injury Response

2018 ◽  
Vol 30 (50) ◽  
pp. 1805209 ◽  
Author(s):  
Francesca L. Maclean ◽  
Georgina M. Ims ◽  
Malcolm K. Horne ◽  
Richard J. Williams ◽  
David R. Nisbet
Keyword(s):  
Brain Injury ◽  
Injury Response ◽  
Anti Inflammatory ◽  
The Brain

scholarly journals Exercise conditioned plasma dampens inflammation via clusterin and boosts memory

2019 ◽  
Author(s):  
Zurine De Miguel ◽  
Michael J. Betley ◽  
Drew Willoughby ◽  
Benoit Lehallier ◽  
Niclas Olsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Aging ◽  
Animal Health ◽  
Brain Inflammation ◽  
Cognitively Impaired ◽  
Complement Cascade ◽  
Striking Increase ◽  
Cognitive Benefits ◽  
Anti Inflammatory ◽  
The Brain

Physical exercise seems universally beneficial to human and animal health, slowing cognitive aging and neurodegeneration. Cognitive benefits are tied to increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms mediating these effects. We discovered “runner” plasma, collected from voluntarily running mice, infused into sedentary mice recapitulates the cellular and functional benefits of exercise on the brain. Importantly, runner plasma reduces baseline neuroinflammatory gene expression and prominently suppresses experimentally induced brain inflammation. Plasma proteomic analysis shows a striking increase in complement cascade inhibitors including clusterin, which is necessary for the anti-inflammatory effects of runner plasma. Cognitively impaired patients participating in structured exercise for 6 months showed higher plasma clusterin levels, which correlated positively with improvements in endurance and aerobic capacity. These findings demonstrate the existence of anti-inflammatory “exercise factors” that are transferrable, benefit the brain, and are present in humans engaging in exercise.

scholarly journals Gut Microbiome Influences The Neuroinflammatory Response To Traumatic Brain Injury

2021 ◽  
Author(s):  
Akshita Jade Kumar ◽  
Supinder Singh Bedi ◽  
Naama Toledano-Furman ◽  
Louis Carrillo ◽  
Fanni Cardenas ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Gut Microbiome ◽  
Central Component ◽  
Post Injury ◽  
Probiotic Treatment ◽  
Anti Inflammatory ◽  
Microglial Response ◽  
The Brain

Abstract Background: Traumatic brain injury (TBI) is a systemic injury that disrupts a complex arrangement of interacting cells in the brain and in the gastrointestinal tract (GI). Disruption in the brain results in neuroinflammation, in which microglia are a central component along with cytokines and other soluble factors [pro and anti-inflammatory microglia (M1:M2)]. Disruption in the GI due to TBI results in a systemic inflammation which is dependent upon the gut microbiome (GM). Gut microbiome can influence microglia in the brain via the gut-brain axis. In order to determine if the microbiome-microglia connections via the gut-brain axis can be modulated, we used probiotics and antibiotics in a rodent TBI model to evaluate the microbiome-microglial connections in acute and chronic experiments.Methods: The temporal effects of treatment (probiotics or antibiotics) were used to evaluate the gut-associated lymphoid tissue (GALT) influence on the microglial response at 72 hours or 21 days after a cortical contusion injury (CCI), a rodent model of TBI. Injured animals received daily probiotics, antibiotics, or no treatment. Sham-injured animals (controls) did not receive any treatment.Results: Twenty-one days of probiotic treatment attenuated the pro-inflammatory response of microglia (M1:M2) after CCI. The post-injury inflammatory response was heightened in the GALT with antibiotic-induced dysbiosis which resulted in amplification of the pro-inflammatory microglial response. Conclusions: Probiotic treatment after TBI is a potential therapeutic in attenuating microglial activation through anti-inflammatory signaling.

scholarly journals Cellular infiltration in traumatic brain injury

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Aftab Alam ◽  
Eric P. Thelin ◽  
Tamara Tajsic ◽  
Danyal Z. Khan ◽  
Abdelhakim Khellaf ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Recovery Phase ◽  
Brain Inflammation ◽  
Cellular Damage ◽  
Injury Site ◽  
Cytokines And Chemokines ◽  
Injured Brain ◽  
Cellular Debris ◽  
The Brain

Abstract Traumatic brain injury leads to cellular damage which in turn results in the rapid release of damage-associated molecular patterns (DAMPs) that prompt resident cells to release cytokines and chemokines. These in turn rapidly recruit neutrophils, which assist in limiting the spread of injury and removing cellular debris. Microglia continuously survey the CNS (central nervous system) compartment and identify structural abnormalities in neurons contributing to the response. After some days, when neutrophil numbers start to decline, activated microglia and astrocytes assemble at the injury site—segregating injured tissue from healthy tissue and facilitating restorative processes. Monocytes infiltrate the injury site to produce chemokines that recruit astrocytes which successively extend their processes towards monocytes during the recovery phase. In this fashion, monocytes infiltration serves to help repair the injured brain. Neurons and astrocytes also moderate brain inflammation via downregulation of cytotoxic inflammation. Depending on the severity of the brain injury, T and B cells can also be recruited to the brain pathology sites at later time points.

scholarly journals Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury

2021 ◽  
Vol 22 (8) ◽  
pp. 4008
Author(s):  
Jaya D. Prasad ◽  
Katherine C. Gunn ◽  
Joanne O. Davidson ◽  
Robert Galinsky ◽  
Scott E. Graham ◽  
...  
Keyword(s):  
Brain Injury ◽  
Immune Responses ◽  
Therapeutic Strategy ◽  
Brain Cell ◽  
Neonatal Immunity ◽  
Neuroprotective Strategies ◽  
Infection And Inflammation ◽  
Anti Inflammatory ◽  
Neurobehavioral Deficits ◽  
Nonspecific Inflammation

Despite the prevalence of preterm brain injury, there are no established neuroprotective strategies to prevent or alleviate mild-to-moderate inflammation-related brain injury. Perinatal infection and inflammation have been shown to trigger acute neuroinflammation, including proinflammatory cytokine release and gliosis, which are associated with acute and chronic disturbances in brain cell survival and maturation. These findings suggest the hypothesis that the inhibition of peripheral immune responses following infection or nonspecific inflammation may be a therapeutic strategy to reduce the associated brain injury and neurobehavioral deficits. This review provides an overview of the neonatal immunity, neuroinflammation, and mechanisms of inflammation-related brain injury in preterm infants and explores the safety and efficacy of anti-inflammatory agents as potentially neurotherapeutics.

scholarly journals PD-L1-expressing astrocytes act as a gate-keeper for neuroinflammation in the central nervous system of mice with traumatic brain injury

2021 ◽  
Author(s):  
Xiang Gao ◽  
Wei Li ◽  
Fahim Syed ◽  
Fang Yuan ◽  
Ping Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
De Novo ◽  
Gene Knockout ◽  
Reactive Astrocytes ◽  
Immune Checkpoints ◽  
Enhanced Production ◽  
The Brain

Background: Tissue damage and cellular destruction are the major events in traumatic brain injury (TBI), which trigger sterile neuroimmune and neuroinflammatory responses in the brain. While appropriate acute and transient neuroimmune and neuroinflammatory responses facilitate the repair and adaptation of injured brain tissues, prolonged and excessive neuroimmune and neuroinflammatory responses exacerbate brain damage. The mechanisms that control the intensity and duration of neuroimmune and neuroinflammatory responses in TBI largely remain elusive. Methods: We used the controlled cortical impact (CCI) model of TBI to study the role of immune checkpoints (ICPs), key regulators of immune homeostasis, in the regulation of neuroimmune and neuroinflammatory responses in the brain in vivo. Results: We found that de novo expression of PD-L1, a potent inhibitory ICP, was robustly and transiently induced in reactive astrocytes, but not in microglial cells, neurons, or oligodendrocyte progenitor cells (OPCs). These PD-L1+ reactive astrocytes were highly enriched to form a dense zone around the TBI lesion. Blockade of PD-L1 signaling enlarged brain tissue cavity size, increased infiltration of inflammatory Ly-6CHigh monocytes/macrophages (M/Mɸ) but not tissue-repairing Ly-6CLow/F4/80+ M/Mɸ, and worsened TBI outcomes in mice. PD-L1 gene knockout enhanced production of CCL2 that interacted with its cognate receptor CCR2 on Ly-6CHigh M/Mϕ to chemotactically recruit these cells into inflammatory sites. Mechanically, PD-L1 signaling in astrocytes likely exhibits dual inhibitory activities for the prevention of excessive neuroimmune and neuroinflammatory responses to TBI through (1) the PD-1/PD-L1 axis to suppress the activity of brain-infiltrating PD-1+ immune cells such as PD-1+ T cells, and (2) PD-L1 reverse signaling to regulate the timing and intensity of astrocyte reactions to TBI. Conclusions: PD-L1+ astrocytes act as a gatekeeper to the brain to control TBI-related neuroimmune and neuroinflammatory responses, thereby opening a novel avenue to study the role of ICP-neuroimmune axes in the pathophysiology of TBI and other neurological disorders.

Sign in / Sign up

Export Citation Format

Share Document