scholarly journals AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3

2015 ◽  
Vol 112 (13) ◽  
pp. 4050-4055 ◽  
Author(s):  
Adam Denes ◽  
Graham Coutts ◽  
Nikolett Lénárt ◽  
Sheena M. Cruickshank ◽  
Pablo Pelegrin ◽  
...  
Keyword(s):  
Brain Injury ◽  
Protein Complexes ◽  
Interleukin 1 ◽  
Adaptor Protein ◽  
Acute Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Pyrin Domain ◽  
Card Domain ◽  
The Brain

Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and is known to exacerbate resulting injury. The activity of interleukin-1 is regulated by multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet the nature of the inflammasomes involved in brain injury is currently unknown. Here, using a rodent model of stroke, we show that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to brain injury. We also show that acute ischemic brain injury is regulated by mechanisms that require ASC (apoptosis-associated speck-like protein containing a CARD), a common adaptor protein for several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3) inflammasome is not involved in this process. These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain.

Interleukin-1 and Ischemic Brain Injury in the Newborn: Development of a Small Molecule Inhibitor of IL-1 Receptor

2008 ◽  
Vol 32 (5) ◽  
pp. 325-333 ◽  
Author(s):  
Christiane Quiniou ◽  
Emna Kooli ◽  
Jean-Sébastien Joyal ◽  
Przemyslaw Sapieha ◽  
Florian Sennlaub ◽  
...  
Keyword(s):  
Brain Injury ◽  
Small Molecule ◽  
Interleukin 1 ◽  
Small Molecule Inhibitor ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Molecule Inhibitor

scholarly journals Necroptosis and microglia activation after chronic ischemic brain injury in mice

2017 ◽  
Vol 15 (2) ◽  
pp. 78-84 ◽  
Author(s):  
Shehong Zhang ◽  
Yuyang Wang ◽  
Hongyu Xie ◽  
Qing Yu ◽  
Junfa Wu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Calcium Binding ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Interferon Γ ◽  
Microglia Activation ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Bilateral Carotid ◽  
The Brain

Microglia, which are the resident macrophages and the first line of defense in the brain, can be activated within hours and migrate toward the injury sites after acute and chronic ischemic brain injury. However, a few studies have reported the interaction between microglia activation and necroptosis signaling following ischemic damage to the brain. In this study, chronic ischemic brain injury was induced by bilateral carotid artery stenosis (BCAS) and mice were sacrificed at 30 days after surgery. Ionized calcium-binding adaptor molecule 1 (IBA1) and glial fibrillary acidic protein (GFAP) immunostaining were performed to determine glial cell activation and inflammatory response. Tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and interleukin-1β (IL-1β) proteins from the brains were examined to confirm inflammatory cytokines after BCAS. RIP1 and RIP3 proteins were detected to determine necroptosis signaling by Western blot. The data suggested that inflammatory responses, microglia activation, and necroptosis signaling are features of brain tissue pathology following BCAS-induced chronic ischemic brain injury.

scholarly journals Ion Channels and Zinc: Mechanisms of Neurotoxicity and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Deborah R. Morris ◽  
Cathy W. Levenson
Keyword(s):  
Brain Injury ◽  
Ion Channels ◽  
Kainate Receptors ◽  
Zinc Toxicity ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
The Central Nervous System ◽  
Excitatory Neurotransmission ◽  
The Brain

Ionotropic glutamate receptors, such as NMDA, AMPA and kainate receptors, are ligand-gated ion channels that mediate much of the excitatory neurotransmission in the brain. Not only do these receptors bind glutamate, but they are also regulated by and facilitate the postsynaptic uptake of the trace metal zinc. This paper discusses the role of the excitotoxic influx and accumulation of zinc, the mechanisms responsible for its cytotoxicity, and a number of disorders of the central nervous system that have been linked to these neuronal ion channels and zinc toxicity including ischemic brain injury, traumatic brain injury, and epilepsy.

Anoxic-Ischemic Encephalopathy

2021 ◽  
pp. 485-488
Author(s):  
Tia Chakraborty ◽  
Jennifer E. Fugate
Keyword(s):  
Cardiac Arrest ◽  
Prognostic Factors ◽  
Brain Injury ◽  
Cardiopulmonary Resuscitation ◽  
Respiratory Arrest ◽  
Clinical State ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
The Brain ◽  
Ischemic Encephalopathy

Anoxic-ischemic brain injury occurs when no blood is flowing to the brain. Neurologists commonly encounter this clinical state when evaluating comatose patients who have had a cardiac arrest and prolonged cardiopulmonary resuscitation attempts. Anoxic-ischemic injury may also occur in primary respiratory arrest or severe hypoxemia (eg, asphyxia, anaphylaxis, drug intoxication), but it is less well understood in these circumstances. This chapter reviews the pathophysiologic factors, clinical management, and prognostic factors in anoxic-ischemic brain injury.

scholarly journals Fyn in Neurodevelopment and Ischemic Brain Injury

2015 ◽  
Vol 37 (4-5) ◽  
pp. 311-320 ◽  
Author(s):  
Renatta Knox ◽  
Xiangning Jiang
Keyword(s):  
Nervous System ◽  
Brain Injury ◽  
Tyrosine Kinases ◽  
Src Family Kinases ◽  
Mutant Mice ◽  
Protein Tyrosine Kinases ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
The Brain ◽  
Nonreceptor Protein Tyrosine Kinases

The Src family kinases (SFKs) are nonreceptor protein tyrosine kinases that are implicated in many normal and pathological processes in the nervous system. The SFKs Fyn, Src, Yes, Lyn, and Lck are expressed in the brain. This review will focus on Fyn, as Fyn mutant mice have striking phenotypes in the brain and Fyn has been shown to be involved in ischemic brain injury in adult rodents and, with our work, in neonatal animals. An understanding of Fyn's role in neurodevelopment and disease will allow researchers to target pathological pathways while preserving protective ones.

scholarly journals Immunomodulation with Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis

2019 ◽  
Vol 28 (7) ◽  
pp. 864-873 ◽  
Author(s):  
Maple L. Shiao ◽  
Ce Yuan ◽  
Andrew T. Crane ◽  
Joseph P. Voth ◽  
Mario Juliano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Injury ◽  
Umbilical Cord Blood ◽  
Ischemic Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Brain Transcriptome ◽  
Blood Stem Cells ◽  
Cord Blood Stem Cells ◽  
The Brain

Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that were significantly differentially expressed after ischemic injury compared with control brains. Following UCBSC treatment, 220 of the 275 differentially expressed genes returned to normal levels. Detailed analysis of these altered transcripts revealed that the vast majority were associated with activation of the immune system following cerebral ischemia which were normalized following UCBSC therapy. Major alterations in gene expression profiles after ischemia include blood-brain-barrier breakdown, cytokine production, and immune cell infiltration. These results suggest that UCBSC protect the brain following ischemic injury by down regulating the aberrant activation of innate and adaptive immune responses.

scholarly journals Lipopolysaccharide Worsens the Prognosis of Experimental Cerebral Ischemia via Interferon Gamma-Induced Protein 10 Recruit in the Acute Stage

2019 ◽  
Author(s):  
Ping Wang ◽  
Jiaqi ZHANG ◽  
Feifei GUO ◽  
Shuang Wang ◽  
Yi ZHANG ◽  
...  
Keyword(s):  
Brain Injury ◽  
Interferon Gamma ◽  
Infarct Volume ◽  
Brain Homogenate ◽  
Acute Stage ◽  
Male Rats ◽  
Ischemic Brain Injury ◽  
Ppi Network ◽  
Ischemic Brain ◽  
The Brain

Abstract Background: Infection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood. Aims: We tried to explore the mechanisms that inflammation caused by infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO). Methods: We used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO.Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT 2 Profiler TM PCR array, and quantitative real-time PCR.The differential genes were subjected to Gene Ontology enrichment analysis and Protein-Protein interaction (PPI) network construction. Results: LPS profoundly aggravated the brain damage after 24 hrs post-MCAO. At the acute stage (Ischemia/Reperfusion 90min/3h), the brain homogenate gene expression of Interleukin 6 (IL-6), Tumor necrosis factor a(TNF-a), Interleukin 1b(IL-1b)and Interferon Gamma-Induced Protein 10 (IP-10)was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO+LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO+LPS group, which was also in an important position with degrees of ³14 in PPI network. Conclusions: It was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 hrs post-MCAO.

scholarly journals Reduced Ischemic Brain Injury in Interleukin-1β Converting Enzyme—Deficient Mice

1998 ◽  
Vol 18 (2) ◽  
pp. 180-185 ◽  
Author(s):  
Gerald P. Schielke ◽  
Guo-Yuan Yang ◽  
Brenda D. Shivers ◽  
A. Lorris Betz
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Interleukin 1 ◽  
Active Form ◽  
Brain Lesion ◽  
Biologically Active ◽  
Ischemic Brain Injury ◽  
Converting Enzyme ◽  
Ischemic Brain

A variety of recent studies suggest a role for both inflammatory cytokines such as interleukin-1 beta (IL-1β), and apoptosis in ischemic brain injury. Because IL-1β converting enzyme (ICE) is required for the conversion of proIL-1β to its biologically active form, and has homology with proteins that regulate apoptosis in invertebrates, we studied the effect of cerebral ischemia on brain injury in mutant mice deficient in the ICE gene (ICE knockout [KO] mice). Focal cerebral ischemia, produced by occlusion of the middle cerebral artery, resulted in brain edema (increased water and sodium content) at 4 hours and a histologically defined brain lesion at 24 hours. Both of these markers of brain injury were significantly reduced in the ICE KO mice as compared to wild-type C57BL/6 mice. Regional cerebral blood flow, determined using the flow tracer, N-isopropyl [methyl 1,3-14C] p-iodoamphetamine (14C-IMP), was similar in the two strains of mice, indicating that the reduced brain injury in the KO mice was not a result of a lesser degree of ischemia. These data show that ICE contributes to the development of ischemic brain damage, and that it plays a role at an early time in the pathologic process. Although the mechanism of this effect is uncertain, our results suggest that pharmacologic inhibition of ICE may be a useful treatment for stroke.

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