scholarly journals Induction of gp91-phox, a Component of the Phagocyte NADPH Oxidase, in Microglial Cells during Central Nervous System Inflammation

2001 ◽  
Vol 21 (4) ◽  
pp. 374-384 ◽  
Author(s):  
Simon P. Green ◽  
Belinda Cairns ◽  
Julie Rae ◽  
Carol Errett-Baroncini ◽  
Jo-Anne S. Hongo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Microglial Cells ◽  
Cns Inflammation ◽  
Nadph Oxidase Complex

Gp91- phox is an integral component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex that generates reactive oxygen species (ROS) in activated circulating phagocytes. The authors previously demonstrated that gp91- phox knockout (KO) mice show significant protection from neuronal injury after cerebral ischemia–reperfusion injury, suggesting a pivotal role for this enzyme. Moreover, results from chimeric mice suggested that elimination of gp91- phox from both circulating phagocytes and a putative central nervous system (CNS) source were required to confer neuroprotection. In the current study, the authors demonstrated gp91- phox–specific immunostaining of perivascular cells in the CNS of control rats. However, after transient cerebral ischemia, gp91- phox–positive phagocytes were observed within the core ischemic region and activated microglial cells were positive in the penumbra. Such activated microglial cells were also gp91- phox–positive in the CNS of a chimpanzee with mild meningitis. Finally, in humans, both normal adult CNS tissues and isolated fetal microglial cells expressed gp91- phox mRNA. These microglia also expressed mRNA for the five other known components that comprise the NADPH oxidase complex. These data strongly suggest that microglial cells may contain a functionally active NADPH oxidase capable of generating ROS during CNS inflammation.

NADPH oxidase inhibitor improves outcome of mechanical reperfusion by suppressing hemorrhagic transformation

2016 ◽  
Vol 9 (5) ◽  
pp. 492-498 ◽  
Author(s):  
Yong-Hua Tuo ◽  
Zhong Liu ◽  
Jian-Wen Chen ◽  
Qing-Yuan Wang ◽  
Song-Lin Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Acute Stroke ◽  
Neuronal Apoptosis ◽  
Mechanical Thrombectomy ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Hemorrhagic Transformation ◽  
Stroke Treatment

BackgroundSevere hemorrhagic transformation (HT) after mechanical thrombectomy predicts a poor clinical outcome in acute ischemic stroke. To better understand the mechanism of HT, we investigated the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in HT after reperfusion during acute stroke and whether NOX2/4 inhibitor VAS2870 reduces reperfusion-induced HT after mechanical recanalization.MethodsA model of reperfusion-induced HT was established in rats (n=182) with hyperglycemic challenge and 5 h middle cerebral artery occlusion followed by 19 h reperfusion. NOX inhibitor VAS2870 was delivered intravenously 30 min before reperfusion. Infarct volume, brain water content, HT, neurological score, mortality rate, blood–brain barrier (BBB) damage, neuronal apoptosis, and reactive oxygen species were determined at 24 h after cerebral ischemia. The expressions of NOX1, NOX2, NOX4, and BBB-associated proteins were measured.ResultsNOX2 and NOX4 upregulation and severe HT were observed in hyperglycemic rats after cerebral ischemia/reperfusion. VAS2870 suppressed oxidative stress, neuronal apoptosis, and NOX2/4 upregulation in the ischemic hemisphere. VAS2870 reduced infarct volume (17.2±5.3% vs 37.4±9.2%, p<0.01) and the frequency of reperfusion-induced parenchymal hematoma (29.7% vs 59.5%, p<0.05) at 24 h after ischemia compared with the ischemia/reperfusion group. VAS2870 attenuated brain edema and reduced reperfusion-induced BBB breakdown, resulting in improved neurological outcome (neurological deficit score 1.43±0.50 vs 2.43±0.93, p<0.001) and reduced mortality (11.9% vs 64.1%, p<0.001).ConclusionsNOX2 and NOX4 may mediate HT in rats with large vessel stroke after mechanical reperfusion. Infusion of NOX inhibitor VAS2870 before mechanical thrombectomy represents a novel adjunctive therapeutic strategy to prevent reperfusion-induced HT and improve outcome of acute stroke treatment.

scholarly journals A review of the relationship between long noncoding RNA and post-stroke injury repair

2019 ◽  
Vol 47 (10) ◽  
pp. 4619-4624
Author(s):  
Yao Wang ◽  
Wei-Yi Pan ◽  
Jun-Sheng Ge ◽  
Xiao-Dong Wang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Noncoding Rna ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Regulatory Sequences ◽  
Post Injury ◽  
Injury Repair ◽  
Post Stroke ◽  
The Central Nervous System

Stroke is a cerebrovascular circulation disorder with sudden onset, which causes disorder of ion balance, inflammation, and acidosis, and that in turn induces ischemia-reperfusion injury, influencing the prognosis of stroke patients. Long noncoding RNAs (lncRNAs) are regulatory sequences involved at the transcriptional, post-transcriptional, and epigenetic levels, have high specific expression in the central nervous system, and effectively regulate the development of the central nervous system and progression of diseases. Stroke induces changes in the expression of many lncRNAs. Therefore, lncRNAs play an important role in the complex pathological process of stroke. Exploring lncRNA could facilitate a comprehensive understanding of the pathological mechanism of stroke and the post-injury molecular regulatory network. However, there are few reports on the role of lncRNA in the pathological development of stroke. In the present review, we discuss the association of lncRNA with post-stroke injury repair.

scholarly journals The Roles of GABA in Ischemia-Reperfusion Injury in the Central Nervous System and Peripheral Organs

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Chaoran Chen ◽  
Xiang Zhou ◽  
Jialiang He ◽  
Zhenxing Xie ◽  
Shufang Xia ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Vital Role ◽  
Pathological Process ◽  
Peripheral Organs ◽  
Multiple Organs ◽  
Long Time ◽  
The Central Nervous System

Ischemia-reperfusion (I/R) injury is a common pathological process, which may lead to dysfunctions and failures of multiple organs. A flawless medical way of endogenous therapeutic target can illuminate accurate clinical applications. γ-Aminobutyric acid (GABA) has been known as a marker in I/R injury of the central nervous system (mainly in the brain) for a long time, and it may play a vital role in the occurrence of I/R injury. It has been observed that throughout cerebral I/R, levels, syntheses, releases, metabolisms, receptors, and transmissions of GABA undergo complex pathological variations. Scientists have investigated the GABAergic enhancers for attenuating cerebral I/R injury; however, discussions on existing problems and mechanisms of available drugs were seldom carried out so far. Therefore, this review would summarize the process of pathological variations in the GABA system under cerebral I/R injury and will cover corresponding probable issues and mechanisms in using GABA-related drugs to illuminate the concern about clinical illness for accurately preventing cerebral I/R injury. In addition, the study will summarize the increasing GABA signals that can prevent I/R injuries occurring in peripheral organs, and the roles of GABA were also discussed correspondingly.

scholarly journals NLRC5: A Potential Target for Central Nervous System Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Lu Zhang ◽  
Cui Jiao ◽  
Lingjuan Liu ◽  
Aiping Wang ◽  
Li Tang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Development ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nuclear Factor Κb ◽  
Research Progress ◽  
Cns Infection ◽  
Type I ◽  
Nucleotide Oligomerization

Nucleotide oligomerization domain-like receptors (NLRs), a class of pattern recognition receptors, participate in the host’s first line of defense against invading pathogenic microorganisms. NLR family caspase recruitment domain containing 5 (NLRC5) is the largest member of the NLR family and has been shown to play an important role in inflammatory processes, angiogenesis, immunity, and apoptosis by regulating the nuclear factor-κB, type I interferon, and inflammasome signaling pathways, as well as the expression of major histocompatibility complex I genes. Recent studies have found that NLRC5 is also associated with neuronal development and central nervous system (CNS) diseases, such as CNS infection, cerebral ischemia/reperfusion injury, glioma, multiple sclerosis, and epilepsy. This review summarizes the research progress in the structure, expression, and biological characteristics of NLRC5 and its relationship with the CNS.

Modulation of NADPH oxidase activation in cerebral ischemia/reperfusion injury in rats

2011 ◽  
Vol 1372 ◽  
pp. 92-102 ◽  
Author(s):  
Tiziana Genovese ◽  
Emanuela Mazzon ◽  
Irene Paterniti ◽  
Emanuela Esposito ◽  
Placido Bramanti ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Nadph Oxidase Activation

scholarly journals Immunocytochemical localization of catalase in the central nervous system of the rat.

1995 ◽  
Vol 43 (12) ◽  
pp. 1253-1267 ◽  
Author(s):  
S Moreno ◽  
E Mugnaini ◽  
M P Cerù
Keyword(s):  
Reactive Oxygen Species ◽  
Central Nervous System ◽  
Nervous System ◽  
Reperfusion Injury ◽  
Brain Aging ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Ependymal Cells ◽  
Oxygen Species

Catalase is a marker for peroxisomes, which are ubiquitous cytoplasmic organelles. Although the distribution and features of peroxisomes are well known in liver and kidney, these organelles have been rarely studied in neural tissues. Catalase is an important scavenging enzyme against reactive oxygen species, as it removes H2O2 produced during metabolic processes. Reactive oxygen species are involved in a number of brain lesions and in brain aging. We investigated the distribution of catalase in rat central nervous system by means of a newly developed immunocytochemical procedure for signal enhancement, using an affinity-purified polyclonal antiserum. The data show that catalase immunoreactivity is present in all neural cells, both neuronal and glial, albeit at different concentrations. Among glial cells, ependymal cells and tanycytes of the third ventricle and the median eminence show the most intense immunoreaction; positivity is also found in oligodendrocytes and astrocytes. In general, neurons in the brainstem are relatively more immunoreactive than those in the forebrain although, within these respective brain regions, there are areas with low and high staining intensity. Moreover, within the same area, certain types of neuron appear more immunoreactive than others. The cell bodies in the septal nuclei, pallidum, reticular thalamic nucleus, mesencephalic nucleus of the trigeminal nerve, Deiter's nucleus, locus ceruleus, cranial and spinal motor nuclei, and the Golgi cells of the cerebellar cortex are among the most densely stained neurons. Catalase immunoreactivity of the cell bodies, which presumably is proportional to catalase content, appears to be only partially correlated with cell size or type of neurotransmitter used in the nerve endings; it is likely that other unknown parameters regulate the abundance of the enzyme. In many cases, highly immunoreactive cells correspond to neurons known to be resistant to ischemia-reperfusion injury, whereas weakly stained cells correspond to neurons that are more susceptible to ischemic damage. The amount of catalase may be critical for a protective effect against oxidative stress under pathological conditions, such as ischemia-reperfusion injury.

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