scholarly journals Liraglutide Activates the Nrf2/HO-1 Antioxidant Pathway and Protects Brain Nerve Cells against Cerebral Ischemia in Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Caihong Deng ◽  
Jun Cao ◽  
Jiangquan Han ◽  
Jianguo Li ◽  
Zhaohun Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Diabetic Rats ◽  
Neurological Deficits ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Sprague Dawley ◽  
Significant Difference

This study aimed to determine the effect of liraglutide pretreatment and to elucidate the mechanism of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) signaling after focal cerebral ischemia injury in diabetic rats model. Adult male Sprague-Dawley rats were randomly divided into the sham-operated (S) group, diabetes mellitus ischemia (DM + MCAO) group, liraglutide pretreatment normal blood glucose ischemia (NDM+MCAO+L) group, and liraglutide pretreatment diabetes ischemia (DM + MCAO + L) group. At 48 h after middle cerebral artery occlusion (MCAO), neurological deficits and infarct volume of brain were measured. Oxidative stress brain tissue was determined by superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. The expression levels of Nrf2 and HO-1 of brain tissue were analyzed by western blotting. In the DM + MCAO + L group, neurological deficits scores and cerebral infarct volume seemed to decrease at 48 h after MCAO cerebral ischemia compared with those in DM + MCAO group (P<0.05). In addition, the expression of Nrf2 and HO-1 increased in 48 h at liraglutide pretreatment groups after MCAO cerebral ischemia if compared with those in the DM + MCAO group (P<0.05). Furthermore, the DM + MCAO + L group has no significant difference compared with the NDM + MCAO + L group (P>0.05). To sum up, alleviating effects of liraglutide on diabetes complicated with cerebral ischemia injury rats would be related to Nrf2/HO-1 signaling pathway.

scholarly journals Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage

2018 ◽  
Vol 125 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Chun Li ◽  
Hong Sun ◽  
Guodong Xu ◽  
Kimberly D. McCarter ◽  
Jiyu Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neutrophil Infiltration ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Ischemic Brain Damage ◽  
Mitochondrial Oxidative Stress ◽  
Ischemic Brain

Nicotine may contribute to the pathogenesis of cerebrovascular disease via the generation of reactive oxygen species (ROS). Overproduction of ROS leads to brain damage by intensifying postischemic inflammation. Our goal was to determine the effect of Mito-Tempo, a mitochondria-targeted antioxidant, on ischemic brain damage and postischemic inflammation during chronic exposure to nicotine. Male Sprague-Dawley rats were divided into four groups: control, nicotine, Mito-Tempo-treated control, and Mito-Tempo-treated nicotine. Nicotine (2 mg·kg−1·day−1) was administered via an osmotic minipump for 4 wk. Mito-Tempo (0.7 mg·kg−1·day−1ip) was given for 7 days before cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h. Brain damage and inflammation were evaluated after 24 h of reperfusion by measuring infarct volume, expression of adhesion molecules, activity of matrix metalloproteinase, brain edema, microglial activation, and neutrophil infiltration. Nicotine exacerbated infarct volume and worsened neurological deficits. Nicotine did not alter baseline ICAM-1 expression, matrix metallopeptidase-2 activity, microglia activation, or neutrophil infiltration but increased these parameters after cerebral ischemia. Mito-Tempo did not have an effect in control rats but prevented the chronic nicotine-induced augmentation of ischemic brain damage and postischemic inflammation. We suggest that nicotine increases brain damage following cerebral ischemia via an increase in mitochondrial oxidative stress, which, in turn, contributes to postischemic inflammation.NEW & NOTEWORTHY Our findings have important implications for the understanding of mechanisms contributing to increased susceptibility of the brain to damage in smokers and users of nicotine-containing tobacco products.

scholarly journals Stigmasterol alleviates cerebral ischemia/reperfusion injury by attenuating inflammation and improving antioxidant defenses in rats

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Qilong Liang ◽  
Jun Yang ◽  
Jiaji He ◽  
Xiaoling Chen ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Antioxidant Defenses ◽  
Neurological Deficits ◽  
Inflammatory Factors ◽  
Tunel Staining ◽  
Heme Oxygenase 1 ◽  
Cerebral Ischemia Reperfusion

Abstract Background/aims: The paper aimed to investigate the effects of Stigmasterol on inflammatory factors, antioxidant capacity, and apoptotic signaling pathways in brain tissue of rats with cerebral ischemia/reperfusion (I/R) injury. Methods: The neurological deficits of the rats were analyzed and HE staining was performed. The cerebral infarct volume was calculated by means of TTC staining, and neuronal apoptosis was detected by TUNEL staining. At the same time, the contents of glutathione peroxidase, glutathione, superoxide dismutase (SOD), nitric oxide, and malondialdehyde in brain tissue were measured. The expression of the relevant protein was detected by means of Western blotting. Results: The results showed that the neurological deficit score and infarct area of the I/R rats in the soy sterol treatment group were significantly lower than those in the I/R group. Moreover, the levels of carbon monoxide and malondialdehyde in the soysterol group were significantly lower than those in the I/R group, and the expressions of cyclooxygenase-2 (Cox-2) and NF-κB (p65) in the soysterol group were also significantly lower than those in the I/R group. The expression of Nrf2 (nucleus) and heme oxygenase-1 (HO-1) increased significantly, and the activities of antioxidant enzymes and SOD were increased. In addition, the stigmasterol treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, and up-regulate Bcl-Xl expression. Conclusion: Stigmasterol protects the brain from brain I/R damage by reducing oxidative stress and inflammation.

Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury

2004 ◽  
Vol 286 (6) ◽  
pp. H2442-H2451 ◽  
Author(s):  
Ikuyo Kusaka ◽  
Gen Kusaka ◽  
Changman Zhou ◽  
Mami Ishikawa ◽  
Anil Nanda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Focal Cerebral Ischemia ◽  
Lipid Hydroperoxide ◽  
Neurological Deficits ◽  
Sprague Dawley

The objective of the present study was to examine the role of the angiotensin II type 1 receptor (AT1-R) in the diabetes-aggravated oxidative stress and brain injury observed in a rat model of combined diabetes and focal cerebral ischemia. Diabetes was induced by an injection of streptozotoxin (STZ; 55 mg/kg iv) at 8 wk of age. Two weeks after the induction of diabetes, some animals received continuous subcutaneous infusion of the AT1-R antagonist candesartan (0.5 mg·kg−1·day−1) for 14 days. Focal cerebral ischemia, induced by middle cerebral artery occlusion/reperfusion (MCAO), was conducted at 4 wk after STZ injection. Male Sprague-Dawley rats ( n = 189) were divided into five groups: normal control, diabetes, MCAO, diabetes + MCAO, and diabetes + MCAO + candesartan. The major observations were that 1) MCAO produced typical cerebral infarction and neurological deficits at 24 h that were accompanied by elevation of NAD(P)H oxidase gp91phox and p22phox mRNAs, and lipid hydroperoxide production in the ipsilateral hemisphere; 2) diabetes enhanced NAD(P)H oxidase gp91phox and p22phox mRNA expression, potentiated lipid peroxidation, aggravated neurological deficits, and enlarged cerebral infarction; and 3) candesartan reduced the expression of gp91phox and p22phox, decreased lipid peroxidation, lessened cerebral infarction, and improved the neurological outcome. We conclude that diabetes exaggerates the oxidative stress, NAD(P)H oxidase induction, and brain injury induced by focal cerebral ischemia. The diabetes-aggravated brain injury involves AT1-Rs. We have shown for the first time that candesartan reduces brain injury in a combined model of diabetes and cerebral ischemia.

scholarly journals Sevoflurane Preconditioning against Focal Cerebral Ischemia

2009 ◽  
Vol 110 (6) ◽  
pp. 1271-1278 ◽  
Author(s):  
Jean-Laurent Codaccioni ◽  
Lionel J. Velly ◽  
Chahrazad Moubarik ◽  
Nicolas J. Bruder ◽  
Pascale S. Pisano ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Cerebral Injury ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Sprague Dawley ◽  
Nissl Staining ◽  
Neuroprotective Effects ◽  
Sevoflurane Preconditioning

Background Preconditioning the brain with volatile anesthetics seems to be a viable option for reducing ischemic cerebral injury. However, it is uncertain whether this preconditioning effect extends over a longer period of time. The purpose of this study was to determine if sevoflurane preconditioning offers durable neuroprotection against cerebral ischemia. Methods Rats (Sprague-Dawley) were randomly allocated to two groups: nonpreconditioned control group (n = 44) and preconditioned group (n = 45) exposed to 2.7 vol% sevoflurane (45 min) 60 min before surgery. Animals in both groups were anesthetized with 3.0 vol% sevoflurane and subjected to transient middle cerebral artery occlusion. After 60 min of awake focal ischemia, the filament was removed. Functional neurologic outcome (range 0-18; 0 = no deficit), cerebral infarct size (Nissl staining), and apoptosis (Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling; cleaved caspase-3 staining) were evaluated at 3, 7, and 14 days after ischemia. Results Sevoflurane preconditioning significantly improved functional outcome and reduced infarct volume (109 +/- 43 vs. 148 +/- 56 mm(3)) 3 days after ischemia compared to the control group. However, after 7- and 14-day recovery periods, no significant differences were observed between groups. The number of apoptotic cells was significantly lower in the preconditioned group than in the control group after 3- and 7-day recovery periods. Fourteen days after ischemia, no differences were observed between groups. Conclusion In this model of transient focal cerebral ischemia, sevoflurane preconditioning induced effective but transient neuroprotective effects. Sevoflurane preconditioning also decreased ischemia-induced apoptosis in a more sustained way because it was observed up to 7 days after injury.

scholarly journals A Selective N-Type Calcium Channel Antagonist Reduces Extracellular Glutamate Release and Infarct Volume in Focal Cerebral Ischemia

1995 ◽  
Vol 15 (4) ◽  
pp. 611-618 ◽  
Author(s):  
Shunya Takizawa ◽  
Kazushi Matsushima ◽  
Hitoshi Fujita ◽  
Kazunori Nanri ◽  
Saori Ogawa ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Calcium Channel ◽  
Calcium Channel Antagonist ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Glutamate Release ◽  
Extracellular Glutamate ◽  
Neuroprotective Effects ◽  
Significant Difference ◽  
The Right

Although a number of studies have demonstrated the neuroprotective effects of antagonists of postsynaptic N-methyl-d-aspartate (NMDA) and non-NMDA receptors in cerebral ischemia, little is known about the treatment of cerebral infarction through presynaptic blocking of extracellular glutamate release. We evaluated the effects of a presynaptic selective N-type calcium channel antagonist (SNX-111, given intravenously by continuous infusion at 5 mg/kg/h from 20 min prior to occlusion until 2 h postocclusion) on blood flow, extracellular glutamate, and infarct volume in rats with permanent occlusions of the right middle cerebral and right common carotid arteries plus 1-h transient occlusion of the left common carotid artery. There was no significant difference in CBF in the occluded cortex during the experiment between the treated and vehicle groups. SNX-111 significantly reduced total amount of extracellular glutamate during the experiment and the peak value of the glutamate after occlusion from 44.2 ± 15.8 μ M (mean ± SD) to 21.4 ± 11.4 μ M (p < 0.01). Infusion of SNX-111 also significantly reduced the cortical volume of infarction from 47.2 ± 5.8 to 19.9 ± 7.3% (p < 0.0001). These results suggest that SNX-111 has a protective effect against focal ischemia through the inhibition of glutamate release from presynaptic sites, although SNX-111 may also affect the release of other neurotransmitters.

scholarly journals Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Min Jae Kim ◽  
Seo-Yeon Lee ◽  
Ji Young Hwang ◽  
Hyunha Kim ◽  
Ki-Tae Ha ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Mouse Model ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Immunohistochemical Analysis ◽  
Medicinal Herbs ◽  
Neurological Deficits ◽  
Dependent Manner

Aim. Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods. Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4) was performed following ischemic injury. Results. Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB) breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg), while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1) expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions. These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

scholarly journals Delayed Treatment with Intravenous Basic Fibroblast Growth Factor Reduces Infarct Size following Permanent Focal Cerebral Ischemia in Rats

1995 ◽  
Vol 15 (6) ◽  
pp. 953-959 ◽  
Author(s):  
Marc Fisher ◽  
Mary-Ellen Meadows ◽  
Tuyen Do ◽  
Jens Weise ◽  
Vladimir Trubetskoy ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Focal Cerebral Ischemia ◽  
Brain Temperature ◽  
Infarct Volume ◽  
Fibroblast Growth ◽  
Sprague Dawley ◽  
Arterial Blood

Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 μg/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague–Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 ± 1.0 in vehicle-treated and 1.5 ± 1.3 in bFGF-treated rats (mean ± SD; TV = 12 vs. 11; p = 0.009). Infarct volume was 297 ± 65 mm3 in vehicle- and 143 ± 135 mm3 in bFGF-treated animals ( p = 0.002). During infusion, there was a modest decrease in mean arterial blood pressure but no changes in arterial blood gases or core or brain temperature in bFGF-treated rats. Autoradiography following intravenous administration of 111In-labeled bFGF showed that labeled bFGF crossed the damaged blood–brain barrier to enter the ischemic (but not the nonischemic) hemisphere. Whether the infarct-reducing effects of bFGF depend on intraparenchymal or intravascular mechanisms requires further study.

scholarly journals Astragaloside IV for Experimental Focal Cerebral Ischemia: Preclinical Evidence and Possible Mechanisms

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Hui-Lin Wang ◽  
Qi-Hui Zhou ◽  
Meng-Bei Xu ◽  
Xiao-Li Zhou ◽  
Guo-Qing Zheng
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Quality Score ◽  
Neurological Deficits ◽  
Study Quality ◽  
Astragaloside Iv ◽  
Anti Inflammatory

Astragaloside IV (AST-IV) is a principal component of Radix Astragali seu Hedysari (Huangqi) and exerts potential neuroprotection in experimental ischemic stroke. Here, we systematically assessed the effectiveness and possible mechanisms of AST-IV for experimental acute ischemic stroke. An electronic search in eight databases was conducted from inception to March 2016. The study quality score was evaluated using the CAMARADES. Rev Man 5.0 software was used for data analyses. Thirteen studies with 244 animals were identified. The study quality score of included studies ranged from 3/10 to 8/10. Eleven studies showed significant effects of AST-IV for ameliorating the neurological function score (P<0.05); seven studies for reducing the infarct volume (P<0.05); and three or two studies for reducing the brain water content and Evans blue leakage (P<0.05), respectively, compared with the control. The mechanisms of AST-IV for ischemic stroke are multiple such as antioxidative/nitration stress reaction, anti-inflammatory, and antiapoptosis. In conclusion, the findings of present study indicated that AST-IV could improve neurological deficits and infarct volume and reduce the blood-brain barrier permeability in experimental cerebral ischemia despite some methodological flaws. Thus, AST-IV exerted a possible neuroprotective effect during the cerebral ischemia/reperfusion injury largely through its antioxidant, anti-inflammatory, and antiapoptosis properties.

scholarly journals A20-Binding Inhibitor of NF-κB 1 Ameliorates Neuroinflammation and Mediates Antineuroinflammatory Effect of Electroacupuncture in Cerebral Ischemia/Reperfusion Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xueling Zhou ◽  
Wenhao Lu ◽  
You Wang ◽  
Jiani Li ◽  
Yong Luo
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Cerebral Ischemia Reperfusion ◽  
Neuroprotective Strategy

A20-binding inhibitor of NF-κB 1 (ABIN1) is an inhibitor of NF-κB and exerts anti-inflammatory effect. Electroacupuncture (EA) is considered as a neuroprotective strategy by inhibiting neuroinflammatory damage after cerebral ischemia. This study was performed to explore the role of ABIN1 and investigate whether the ABIN1 is involved in the mechanism of EA in cerebral ischemia/reperfusion (I/R) rats. Male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and received EA after reperfusion once a day. Lentivirus-mediated ABIN1 gene knockdown was used to detect the role of ABIN1 in neuroinflammation after I/R. ABIN1 expression, proinflammatory cytokine levels, microglial activation, neurological function, infarct volumes, and NF-κB activation were assessed. ABIN1 expression was elevated in the peri-infarct cortex and was further upregulated by EA. ABIN1 knockdown increased the levels of proinflammatory cytokines and activation of microglia, worsened neurological deficits, and enlarged the infarct volume. Moreover, ABIN1 was blocked to partially reverse the neuroprotective effect of EA, and this treatment weakened the ability of EA to suppress NF-κB activity. Based on these findings, ABIN1 is a potential suppressor of neuroinflammation and ABIN1 mediates the antineuroinflammatory effect of EA in cerebral I/R rats.

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