scholarly journals Antioxidant CR-6 Protects against Reperfusion Injury after a Transient Episode of Focal Brain Ischemia in Rats

2009 ◽  
Vol 30 (3) ◽  
pp. 638-652 ◽  
Author(s):  
Fernando J Pérez-Asensio ◽  
Xavier de la Rosa ◽  
Francesc Jiménez-Altayó ◽  
Roser Gorina ◽  
Emili Martínez ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Neurological Deficit ◽  
Nitrosative Stress ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Reactive Hyperemia ◽  
Sprague Dawley ◽  
Neutrophil Accumulation ◽  
Oxidative And Nitrosative Stress ◽  
Doppler Flowmetry

Oxidative and nitrosative stress are targets for intervention after ischemia/reperfusion. The aim of this study was to explore the effect of CR-6, a vitamin-E analogue that is antioxidant and scavenger of nitrogen-reactive species. Sprague–Dawley rats had the middle cerebral artery (MCA) occluded either for 90 mins or permanently. Cortical perfusion was continuously monitored by laser–Doppler flowmetry. CR-6 (100 mg/kg) was administered orally either at 2 and 8 h after MCA occlusion, or at 2 h only. Infarct volume, neurological deficit, and signs of reperfusion injury were evaluated. CR-6 was detected in plasma and brain by HPLC. CR-6 reduced glutathione consumption in the ischemic brain and superoxide generation in the isolated MCA. CR-6 decreased infarct volume and attenuated the neurological deficit at 1 and 7 days after ischemia/reperfusion, but not after permanent ischemia. Immediately after reperfusion, cortical blood flow values returned to their baseline (±20%) in several animals, whereas others showed hyper-perfusion (>20% of baseline). Reactive hyperemia was associated with adverse events such as increased cortical BBB leakage, edema, protein nitrotyrosination, COX-2 expression, and neutrophil accumulation; and with a poorer outcome, and CR-6 attenuated these effects. In conclusion, oral CR-6 administration after transient ischemia protects the brain from reperfusion injury.

ADAMTS13 Gene Deletion Aggravates Ischemic Brain Damage

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 260-260 ◽  
Author(s):  
Kenji Nishio ◽  
Masayuki Fujioka ◽  
Kazuhide Hayakawa ◽  
Kenichi Mishima ◽  
Michihiro Fujiwara ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Arterial Occlusion ◽  
Neurological Deficits ◽  
Doppler Flowmetry ◽  
Adamts13 Deficiency ◽  
Cerebral Arterial Occlusion ◽  
The Brain

Abstract Background: The proteolytic activity of human ADAMTS13 regulates the size of von Willebrand factor (VWF) multimers, controlling excessive platelet aggregation and preventing microvascular thrombus formation. Deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP) and patients with TTP often have neurological deficits such as stupor or coma. Therefore, ADAMTS13 appears necessary for vascular homeostasis in the brain and may also influence the response to brain injury during ischemic stroke. Method and Result: We investigated the role of ADAMTS13 in a mouse middle cerebral arterial occlusion (MCAO) model of ischemia-reperfusion injury in the brain. We compared 24 wild type mice (WT) and 24 ADAMTS13 gene deleted mice (KO), which are healthy and fertile. All mice were males 6–8 weeks of age. Investigators were blinded to the genotype until all analyses were finished. We applied MCAO for 30 minutes followed by 23.5 hours of reperfusion. The cerebral blood flow (CBF) around the cortex of the ischemic region was measured by laser Doppler flowmetry for 60 minutes after MCAO. In both WT and KO mice, the CBF decreased to less than 20% of baseline during MCAO and returned to normal immediately after reperfusion. However, during the subsequent 30 min the CBF decreased to 34.6±5.8% of baseline for KO mice compared to 83.2±6.8% of baseline for WT mice (P < 0.01) and remained significantly decreased at 24 hours, suggesting that ADAMTS13 deficiency promotes thrombosis after reperfusion injury. The infarction volumes of the brain were determined from the area not stained by 2,3,5,-triphenyltetrazolium chloride (TTC) 24 hours after MCAO. KO mice had significantly increased volume of brain infarction compared with WT (31.0±6.5mm3 vs 11.4±1.9 mm3, P < 0.01). The degree of post-ischemic inflammation was estimated by Western blotting of plasma HMGB1 (high-mobility group box1) 24 hours after MCAO. Plasma HMGB1 was increased to 34.4 ± 5.3 ng/ml in KO mice, compared to 19.6 ± 3.5 ng/ml in WT mice (P < 0.05). The KO and WT mice did not differ during the MCAO procedure in body temperature, survival (80% vs 85%) at 24 hours, prothrombin time, arterial pH, pO2 or pCO2. Conclusion: ADAMTS13 deficiency aggravates the extent of persistent brain ischemia, infarct volume and inflammatory response after brief MCAO. Therefore, ADAMTS13 plays a neuroprotective role against ischemia-reperfusion injury.

scholarly journals Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR

2017 ◽  
Vol 5 (6) ◽  
pp. 131-131 ◽  
Author(s):  
Jan F. Gielis ◽  
Paul A. J. Beckers ◽  
Jacco J. Briedé ◽  
Paul Cos ◽  
Paul E. Van Schil
Keyword(s):  
Reperfusion Injury ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxidative And Nitrosative Stress ◽  
Pulmonary Ischemia

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Brain Damage ◽  
Neurological Deficit ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Degradation Products ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

scholarly journals Methane and Inflammation - A Review (Fight Fire with Fire)

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Marietta Zita Poles ◽  
László Juhász ◽  
Mihály Boros
Keyword(s):  
Stress Responses ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion ◽  
Signalling Pathways ◽  
Experimental Conditions ◽  
Neuroprotective Effects ◽  
Oxidative And Nitrosative Stress ◽  
Carbohydrate Fermentation ◽  
Insight Into

AbstractMammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.

scholarly journals Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin Guo ◽  
Zhixuan Huang ◽  
Lijuan Huang ◽  
Jia Liang ◽  
Peng Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Targeted Delivery ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Therapeutic Drug ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background The incidence of ischemic stroke in the context of vascular disease is high, and the expression of growth-associated protein-43 (GAP43) increases when neurons are damaged or stimulated, especially in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Experimental design We bioengineered neuron-targeting exosomes (Exo) conjugated to a monoclonal antibody against GAP43 (mAb GAP43) to promote the targeted delivery of quercetin (Que) to ischemic neurons with high GAP43 expression and investigated the ability of Exo to treat cerebral ischemia by scavenging reactive oxygen species (ROS). Results Our results suggested that Que loaded mAb GAP43 conjugated exosomes (Que/mAb GAP43-Exo) can specifically target damaged neurons through the interaction between Exo-delivered mAb GAP43 and GAP43 expressed in damaged neurons and improve survival of neurons by inhibiting ROS production through the activation of the Nrf2/HO-1 pathway. The brain infarct volume is smaller, and neurological recovery is more markedly improved following Que/mAb GAP43-Exo treatment than following free Que or Que-carrying exosome (Que-Exo) treatment in a rat induced by MCAO/R. Conclusions Que/mAb GAP43-Exo may serve a promising dual targeting and therapeutic drug delivery system for alleviating cerebral ischemia/reperfusion injury.

MicroRNA-330-5p inhibits NLRP3 inflammasome-mediated myocardial ischemia-reperfusion injury by targeting TIM3

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Zuo ◽  
R Tian ◽  
Q Chen ◽  
L Wang ◽  
Q Gu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is one of the leading causes of human death. Nod-like receptor protein-3 (NLRP3) inflammasome signaling pathway involved in the pathogenesis of MIRI. However, the upstream regulating mechanisms of NLRP3 at molecular level remains unknown. Purpose This study investigated the role of microRNA330-5p (miR-330-5p) in NLRP3 inflammasome-mediated MIRI and the associated mechanism. Methods Mice underwent 45 min occlusion of the left anterior descending coronary artery followed by different times of reperfusion. Myocardial miR-330-5p expression was examined by quantitative polymerase chain reaction (PCR), and miR-330-5p antagomir and agomir were used to regulate miR-330-5p expression. To evaluate the role of miR-330-5p in MIRI, Evans Blue (EB)/2, 3, 5-triphenyltetrazolium chloride (TTC) staining, echocardiography, and immunoblotting were used to assess infarct volume, cardiac function, and NLRP3 inflammasome activation, respectively. Further, in vitro myocardial ischemia-reperfusion model was established in cardiomyocytes (H9C2 cell line). A luciferase binding assay was used to examine whether miR-330-5p directly bound to T-cell immunoglobulin domain and mucin domain-containing molecule-3 (TIM3). Finally, the role of miR-330-5p/TIM3 axis in regulating apoptosis and NLRP3 inflammasome formation were evaluated using flow cytometry assay and immunofluorescence staining. Results Compared to the model group, inhibiting miR-330-5p significantly aggravated MIRI resulting in increased infarct volume (58.09±6.39% vs. 37.82±8.86%, P&lt;0.01) and more severe cardiac dysfunction (left ventricular ejection fraction [LVEF] 12.77%±6.07% vs. 27.44%±4.47%, P&lt;0.01; left ventricular end-diastolic volume [LVEDV] 147.18±25.82 vs. 101.31±33.20, P&lt;0.05; left ventricular end-systolic volume [LVESV] 129.11±30.17 vs. 74.29±28.54, P&lt;0.05). Moreover, inhibiting miR-330-5p significantly increased the levels of NLRP3 inflammasome related proteins including caspase-1 (0.80±0.083 vs. 0.60±0.062, P&lt;0.05), interleukin (IL)-1β (0.87±0.053 vs. 0.79±0.083, P&lt;0.05), IL-18 (0.52±0.063 vs. 0.49±0.098, P&lt;0.05) and tissue necrosis factor (TNF)-α (1.47±0.17 vs. 1.03±0.11, P&lt;0.05). Furthermore, TIM3 was confirmed as a potential target of miR-330-5p. As predicted, suppression of TIM3 by small interfering RNA (siRNA) ameliorated the anti-miR-330-5p-mediated apoptosis of cardiomyocytes and activation of NLRP3 inflammasome signaling pathway (Figure 1). Conclusion Overall, our study indicated that miR-330-5p/TIM3 axis involved in the regulating mechanism of NLRP3 inflammasome-mediated myocardial ischemia-reperfusion injury. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China Grants

Abstract 193: Antithrombin Perfluorocarbon Nanoparticles Ameliorate Renal Injury Following Transient Warm Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Chandu Vemuri ◽  
Junjie Chen ◽  
Rohun U Palekar ◽  
John S Allen ◽  
Xiaoxia Yang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Warm Ischemia ◽  
P Value ◽  
Sprague Dawley ◽  
Histologic Analysis ◽  
Microvascular Thrombosis

Objective: Thrombin mediated microvascular thrombosis plays a crucial role in the pathogenesis of acute renal reperfusion injury following transient ischemia. We hypothesize that anti-thrombin nanoparticles will ameliorate acute renal injury by inhibiting microvascular thrombosis. Methods: Adult, male Sprague Dawley rats were randomized into two groups of 5 to receive tail vein injections of saline or nanoparticles loaded with Phe[D]-Pro-Arg-Chloromethylketone (NP-PPACK). Immediately following injection, all animals underwent operative bilateral renal artery occlusion to create 45 minutes of warm ischemia, followed by restoration of renal blood flow. Blood samples were drawn daily and animals were euthanized on day 1 or 7 for histologic analysis of kidney injury (H&E, TUNEL and thrombin staining). Results: Histologic analysis of renal tissue revealed significant apoptosis, necrosis and thrombin accumulation 1 day after ischemia-reperfusion, confirming acute kidney injury. The peak creatinine (mg/dl) on day 1 was significantly lower in NP-PPACK treated animals (0.57 +/- 0.07 (SEM)) than in saline treated controls (1.40 +/- 0.20 (SEM); p-value <0.01). Furthermore, animals treated with NP-PPACK continued to exhibit less renal dysfunction for 7 days after injury (Figure 1). Conclusion: Histologically confirmed intrarenal thrombosis was detected one day after ischemia-reperfusion injury. Targeted inhibition of thrombin with NP-PPACK prevented a decline in renal function following transient occlusion. Future work will focus on defining the underlying mechanisms of this effect.

scholarly journals Protective effect of alpha lipoic acid on diabetic nephropathy in rats

2019 ◽  
Vol 20 (3) ◽  
pp. 19-23
Author(s):  
Samar Yabes ◽  
Mohamed EL-Adl ◽  
Mohamed Hamed ◽  
Gehad El-Sayed
Keyword(s):  
Diabetic Nephropathy ◽  
Lipoic Acid ◽  
Nitrosative Stress ◽  
Acid Group ◽  
Controlled Study ◽  
Alpha Lipoic Acid ◽  
Sprague Dawley ◽  
Glycemic Status ◽  
Oxidative And Nitrosative Stress ◽  
Tissue Samples

Objective: To evaluate the protective role of alpha lipoic acid in rats affected with experimentally-induced diabetes and secondarily complicated with nephropathy. Design: Randomized controlled study. Animals: Forty-eight Sprague Dawley rats. Procedures: Rats were allocated randomly into four groups (12 each); Control rats (Group 1); alpha lipoic acid (ALA) supplemented rats (Group 2); rats with induced diabetic nephropathy (Group 3), and rats with diabetic nephropathy and supplemented with alpha lipoic acid (Group 4). After one month of experimental induction, serum, plasma and renal tissue samples were harvested to determine glycemic status, renal damage markers, antioxidant status, oxidative and nitrosative stress markers, apoptotic marker and histopathology of kidney tissues. Results: In comparison with non-supplemented diabetic rats, alpha lipoic acid reduced renal malondialdehyde (5.74± 0.26 vs 11.3± 1.96 nmol/g. tissue) and renal nitric oxide (30.06± 2.07 vs 36.6± 1.07 nmol/g. tissue). ALA significantly improved the antioxidant enzyme activity (catalase and reduced glutathione), glycemic status, and decreased caspase 3 concentration (P<0.05). Conclusion and clinical relevance: Alpha lipoic acid may be an alternative intervention to alleviate nephropathy as a complication of diabetes. Further studies need to be done in naturally occurring cases.

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