MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2

Acute focal ischemia is a main factor of pathogenesis of a number of widespread cardiovascular and cerebrovascular diseases, in particular, myocardial infarction and ischemic stroke. It is known that under the conditions of ischemia expression of intracellular heat shock proteins (HSPs), especially HSP70, grows greatly irrespective of the cell type. This stress-induced cell response is connected with cytoprotective properties of HSP70. The protective functions of HSP70 contribute to the cell survival under adverse conditions and inhibit development of programmed cell death. It was shown, that the level of HSP70 increases in cardiomyocytes and brain cells in response to ischemia, that was connected with cardioprotective and neuroprotective effects. Besides, in recent years, clinical studies of HSP70 have demonstrated elevated level of HSP70 in peripheral blood lymphocytes in groups of patients with ischemic stroke and myocardial infarction. This review indicates that HSP70 can serve as a target for developing new approaches to diagnostics and therapy of cardiovascular and cerebrovascular diseases.

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NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats

Neural Plasticity ◽

10.1155/2019/3591605 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Zheng-De Du ◽

Wei Wei ◽

Shukui Yu ◽

Qing-Ling Song ◽

Ke Liu ◽

...

Keyword(s):

Oxidative Damage ◽

Nadph Oxidase ◽

Auditory Cortex ◽

Auditory System ◽

Auditory Brainstem ◽

Secondary Symptom ◽

Zucker Diabetic Fatty Rats ◽

Brainstem Response ◽

Zdf Rats ◽

Nadph Oxidase 2

Clinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker diabetic fatty (ZDF) rats were used as a T2DM rat model to observe ultrastructural alterations in the auditory cortex and investigate possible mechanisms underlying CAS damage in T2DM. The auditory brainstem response (ABR) of ZDF rats was found to be markedly elevated in low (8 kHz) and high (32 kHz) frequencies. Protein expression of NADPH oxidase 2 (NOX2) and its matching subunits P22phox, P47phox, and P67phox was increased in the auditory cortex of ZDF rats. Expression of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, was also increased in the neuronal mitochondria of the auditory cortex of ZDF rats. Additionally, decreases in the mitochondrial total antioxidant capabilities (T-AOC), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (MMP) were detected in the auditory cortex of ZDF rats, suggesting mitochondrial dysfunction. Transmission electron microscopy results indicated that ultrastructural damage had occurred to neurovascular units and mitochondria in the auditory cortex of ZDF rats. Furthermore, cytochrome c (Cyt c) translocation from mitochondria to cytoplasm and caspase 3-dependent apoptosis were also detected in the auditory cortex of ZDF rats. Consequently, the study demonstrated that T2DM may cause morphological damage to the CAS and that NOX2-associated mitochondrial oxidative damage and apoptosis may be partly responsible for this insult.

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Nrf2 promotes reparative angiogenesis through regulation of NADPH oxidase-2 in oxygen-induced retinopathy

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2016.08.013 ◽

2016 ◽

Vol 99 ◽

pp. 234-243 ◽

Cited By ~ 27

Author(s):

Yanhong Wei ◽

Junsong Gong ◽

Zhenhua Xu ◽

Elia J. Duh

Keyword(s):

Nadph Oxidase ◽

Oxygen Induced Retinopathy ◽

Nadph Oxidase 2 ◽

Reparative Angiogenesis

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The Effects ofChunghyul-Dan(A Korean Medicine Herbal Complex) on Cardiovascular and Cerebrovascular Diseases: A Narrative Review

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/2601740 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Woo-Sang Jung ◽

Seungwon Kwon ◽

Seung-Yeon Cho ◽

Seong-Uk Park ◽

Sang-Kwan Moon ◽

...

Keyword(s):

Ischemic Stroke ◽

Ethanol Extract ◽

Inhibitory Effect ◽

Cerebrovascular Diseases ◽

Stroke Recurrence ◽

Neuroprotective Effects ◽

Clinical Safety ◽

Endogenous Catecholamine ◽

Rhei Rhizoma ◽

Coa Reductase

Chunghyul-dan(CHD) is a herbal complex containing 80% ethanol extract and is composed ofScutellariae Radix,Coptidis Rhizoma,Phellodendri Cortex,Gardeniae Fructus, andRhei Rhizoma. We have published several experimental and clinical research articles on CHD. It has shown antilipidemic, antihypertensive, antiatherosclerotic, and inhibitory effects on ischemic stroke recurrence with clinical safety in the previous studies. The antilipidemic effect of CHD results from 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and pancreatic lipase-inhibitory activity. The antihypertensive effect likely results from the inhibitory effect on endogenous catecholamine(s) release and harmonization of all components showing the antihypertensive effects. Furthermore, anti-inflammatory and antioxidant effects on endothelial cells are implicated to dictate the antiatherosclerotic effects of CHD. It also showed neuroprotective effects on cerebrovascular and parkinsonian models. These effects of CHD could be helpful for the prevention of the recurrence of ischemic stroke. Therefore, we suggest that CHD could be a promising medication for treating and preventing cerebrovascular and cardiovascular diseases. However, to validate and better understand these findings, well-designed clinical studies are required.

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Neuroprotective Effects of Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), in Ischemic Stroke of Rats

Journal of Agricultural and Food Chemistry ◽

10.1021/jf204909p ◽

2012 ◽

Vol 60 (8) ◽

pp. 1937-1944 ◽

Cited By ~ 52

Author(s):

Ting-Lin Yen ◽

Chung-King Hsu ◽

Wan-Jung Lu ◽

Cheng-Ying Hsieh ◽

George Hsiao ◽

...

Keyword(s):

Ischemic Stroke ◽

Humulus Lupulus ◽

Neuroprotective Effects

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Temporospatial production of reactive oxygen species in articular chondrocytes is induced by the endocytosis of fibronectin fragments, alpha 5 beta 1 integrin and NADPH oxidase 2

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2021.02.159 ◽

2021 ◽

Vol 29 ◽

pp. S114-S115

Author(s):

M.Z Miao ◽

J.A. Collins ◽

E.M. Bahnson ◽

B.O. Diekman ◽

P.Q. Su ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Articular Chondrocytes ◽

Reactive Oxygen ◽

Oxygen Species ◽

Fibronectin Fragments ◽

Beta 1 Integrin ◽

Nadph Oxidase 2

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Abstract TMP46: Is There an Effect of Statins on Ischemic Stroke Functional Outcomes in the Oldest Old?

Stroke ◽

10.1161/str.48.suppl_1.tmp46 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Matthew Alcusky ◽

Anne L Hume ◽

Kate L Lapane

Keyword(s):

Ischemic Stroke ◽

Functional Status ◽

Functional Outcomes ◽

Acute Treatment ◽

Functional Dependence ◽

Oldest Old ◽

Health Benefit ◽

Neuroprotective Effects ◽

Data Set ◽

Statin Use

Background: The net health benefit of statin use in the oldest patients remains controversial. Preclinical models and previous clinical studies have suggested statins may exhibit neuroprotective effects in stroke, however evidence in the very old remains limited. Our objective was to compare changes in functional status before and after acute ischemic stroke (AIS) between statin users and non-users in a national cohort. Methods: A patient’s first hospitalization for AIS from 04/01/11 to 12/31/2012 was selected from Medicare Part A claims. Patients with a pre-hospitalization nursing home Minimum Data Set assessment and a post-hospitalization assessment in a skilled nursing facility were included. Pre-stroke statin exposure was defined using Part D claims. Functional status was measured continuously and categorically (dependent:<20, partially dependent(PD):20-59, assisted independent(AI):60-100) using Shah’s modified Barthel Index (mBI). Multivariable logistic regression examined the association of statins with a minimum clinically important mBI decrease of 10 points among non-dependent patients. Results: Among 10,203 patients with an assessment before hospitalization, 7.2% died, and 48.7% were included (mean age: 83.6±9.6; 74.5% women). Statin use was common (36.5%), while acute treatment was infrequent (thrombolysis: 4.9%; thrombectomy: 0.1%). The distribution of functional dependence, PD, and AI shifted from 17.3%, 56.1%, and 26.7% at baseline to 49.7%, 44.4%, and 5.9% post-stroke, respectively. A consistent association with 10-point mBI decline was observed for statin exposure among all non-dependent (OR: 0.8; 95%CI: 0.7-1.0) and within strata of PD (OR:0.8; 95%CI: 0.7-1.0) and AI patients (OR: 0.8; 95%CI: 0.5-1.3). In contrast, acute treatment was more strongly associated with function in AI (OR: 0.5; 95%CI: 0.2-1.0) versus PD patients (OR: 1.0; 95%CI: 0.7-1.5). Conclusion: In this high-burden population, our results are suggestive of a possible protective association for pre-stroke statin exposure. Further research is needed to examine temporal and dose-response relationships between statin exposure and functional outcomes across diverse patient populations.

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Protective effects of the angiotensin II AT2 receptor agonist compound 21 in ischemic stroke: a nose-to-brain delivery approach

Clinical Science ◽

10.1042/cs20180100 ◽

2018 ◽

Vol 132 (5) ◽

pp. 581-593 ◽

Cited By ~ 11

Author(s):

Douglas M. Bennion ◽

Chad H. Jones ◽

Alex N. Dang ◽

Jacob Isenberg ◽

Justin T. Graham ◽

...

Keyword(s):

Ischemic Stroke ◽

Angiotensin Ii ◽

Receptor Agonist ◽

At2 Receptor ◽

Protective Effects ◽

Neuroprotective Effects ◽

Receptor Agonists ◽

Compound 21 ◽

Neuroprotective Actions

Significant neuroprotective effects of angiotensin II type 2 (AT2) receptor (AT2 receptor) agonists in ischemic stroke have been previously demonstrated in multiple studies. However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular (ICV) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2 receptor agonists are blood–brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver the selective AT2 receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1 (ET-1)-induced ischemic stroke. The results obtained from the present study indicated that C21 applied N2B entered the cerebral cortex and striatum within 30 min in amounts that are therapeutically relevant (8.4–9 nM), regardless of whether BBB was intact or disintegrated. C21 was first applied N2B at 1.5 h after stroke indeed provided neuroprotection, as evidenced by a highly significant, 57% reduction in cerebral infarct size and significant improvements in Bederson and Garcia neurological scores. N2B-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2 receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective in certain human central nervous system diseases, the N2B application of AT2 receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.

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