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.

A Critical Review of Models of Perinatal Infection

2015 ◽  
Vol 37 (4-5) ◽  
pp. 289-304 ◽  
Author(s):  
Justin M. Dean ◽  
Zhongjie Shi ◽  
Bobbi Fleiss ◽  
Katherine C. Gunn ◽  
Floris Groenendaal ◽  
...  
Keyword(s):  
Brain Injury ◽  
Time Course ◽  
Clinical Evidence ◽  
Postnatal Life ◽  
Perinatal Brain Injury ◽  
Neuroprotective Strategies ◽  
Infection And Inflammation ◽  
Precise Time ◽  
Nonspecific Inflammation

One of the central, unanswered questions in perinatology is why preterm infants continue to have such poor long-term neurodevelopmental, cognitive and learning outcomes, even though severe brain injury is now rare. There is now strong clinical evidence that one factor underlying disability may be infection, as well as nonspecific inflammation, during fetal and early postnatal life. In this review, we examine the experimental evidence linking both acute and chronic infection/inflammation with perinatal brain injury and consider key experimental determinants, including the microglia response, relative brain and immune maturity and the pattern of exposure to infection. We highlight the importance of the origin and derivation of the bacterial cell wall component lipopolysaccharide. Such experimental paradigms are essential to determine the precise time course of the inflammatory reaction and to design targeted neuroprotective strategies to protect the perinatal brain from infection and inflammation.

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 Crosstalk between Environmental Inflammatory Stimuli and Non-Coding RNA in Cancer Occurrence and Development

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4436
Author(s):  
Tingting Xu ◽  
Mengyan Xie ◽  
Xinming Jing ◽  
Jiahua Cui ◽  
Xi Wu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Air Pollutants ◽  
Therapeutic Strategy ◽  
Tumor Development ◽  
Causative Role ◽  
Cancer Occurrence ◽  
Non Coding Rna ◽  
Inflammatory Stimuli ◽  
Infection And Inflammation ◽  
Non Coding Rnas

There is a clear relationship between inflammatory response and different stages of tumor development. Common inflammation-related carcinogens include viruses, bacteria, and environmental mutagens, such as air pollutants, toxic metals, and ultraviolet light. The expression pattern of ncRNA changes in a variety of disease conditions, including inflammation and cancer. Non-coding RNAs (ncRNAs) have a causative role in enhancing inflammatory stimulation and evading immune responses, which are particularly important in persistent pathogen infection and inflammation-to-cancer transformation. In this review, we investigated the mechanism of ncRNA expression imbalance in inflammation-related cancers. A better understanding of the function of inflammation-associated ncRNAs may help to reveal the potential of ncRNAs as a new therapeutic strategy.

scholarly journals Traditional Chinese Medicine Protects against Cytokine Production as the Potential Immunosuppressive Agents in Atherosclerosis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yan Ren ◽  
Wei Qiao ◽  
Dongliang Fu ◽  
Zhiwei Han ◽  
Wei Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Therapeutic Strategy ◽  
Immunosuppressive Agents ◽  
Critical Factor ◽  
Chronic Inflammatory Disease ◽  
Atherosclerosis Progression ◽  
Adaptive Immune ◽  
Chinese Medicinal Plants ◽  
Anti Inflammatory ◽  
Accelerate Atherosclerosis

Atherosclerosis is a chronic inflammatory disease caused by dyslipidemia and mediated by both innate and adaptive immune responses. Inflammation is a critical factor at all stages of atherosclerosis progression. Proinflammatory cytokines accelerate atherosclerosis progression, while anti-inflammatory cytokines ameliorate the disease. Accordingly, strategies to inhibit immune activation and impede immune responses towards anti-inflammatory activity are an alternative therapeutic strategy to conventional chemotherapy on cardiocerebrovascular outcomes. Since a number of Chinese medicinal plants have been used traditionally to prevent and treat atherosclerosis, it is reasonable to assume that the plants used for such disease may suppress the immune responses and the resultant inflammation. This review focuses on plants that have immunomodulatory effects on the production of inflammatory cytokine burst and are used in Chinese traditional medicine for the prevention and therapy of atherosclerosis.

scholarly journals Inflammatory Neuropsychiatric Disorders and COVID-19 Neuroinflammation

2021 ◽  
pp. 1-55
Author(s):  
Siu Wa Tang ◽  
Daiga Helmeste ◽  
Brian Leonard
Keyword(s):  
Immune Responses ◽  
Clinical Management ◽  
Neuronal Damage ◽  
Treatment Resistance ◽  
Neuropsychiatric Disorders ◽  
Acute Stage ◽  
Management Approach ◽  
Neuropsychiatric Diseases ◽  
Anti Inflammatory

Abstract Neuropsychiatric sequalae to COVID-19 infection are beginning to emerge, like previous Spanish influenza and SARS episodes. Streptococcal infection in pediatric patients causing OCD (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, wide-spread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long term specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favorable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease modifying therapies are increasingly being applied to neuropsychiatric diseases characterized by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Enriching neural stem cell and anti‐inflammatory glial phenotypes with electrical stimulation after traumatic brain injury in male rats

2021 ◽  
Author(s):  
Eunyoung Park ◽  
Johnathan G. Lyon ◽  
Melissa Alvarado‐Velez ◽  
Martha I. Betancur ◽  
Nassir Mokarram ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cell ◽  
Electrical Stimulation ◽  
Brain Injury ◽  
Neural Stem Cell ◽  
Male Rats ◽  
Anti Inflammatory

scholarly journals Targeted Drug Delivery Technologies Potentiate the Overall Therapeutic Efficacy of an Indole Derivative in a Mouse Cystic Fibrosis Setting

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1601
Author(s):  
Matteo Puccetti ◽  
Marilena Pariano ◽  
Giorgia Renga ◽  
Ilaria Santarelli ◽  
Fiorella D’Onofrio ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Targeted Drug Delivery ◽  
Fungal Infections ◽  
Murine Models ◽  
Multisystem Disease ◽  
Aryl Hydrocarbon ◽  
Target Organs ◽  
Infection And Inflammation ◽  
Anti Inflammatory ◽  
Inflammatory Toxicity

Inflammation plays a major role in the pathophysiology of cystic fibrosis (CF), a multisystem disease. Anti-inflammatory therapies are, therefore, of interest in CF, provided that the inhibition of inflammation does not compromise the ability to fight pathogens. Here, we assess whether indole-3-aldehyde (3-IAld), a ligand of the aryl hydrocarbon receptor (AhR), may encompass such an activity. We resorted to biopharmaceutical technologies in order to deliver 3-IAld directly into the lung, via dry powder inhalation, or into the gut, via enteric microparticles, in murine models of CF infection and inflammation. We found the site-specific delivery of 3-IAld to be an efficient strategy to restore immune and microbial homeostasis in CF organs, and mitigate lung and gut inflammatory pathology in response to fungal infections, in the relative absence of local and systemic inflammatory toxicity. Thus, enhanced delivery to target organs of AhR agonists, such as 3-IAld, may pave the way for the development of safe and effective anti-inflammatory agents in CF.

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