scholarly journals Exendin-4, a Glucagon-Like Peptide-1 Receptor Agonist, Provides Neuroprotection in Mice Transient Focal Cerebral Ischemia

2011 ◽  
Vol 31 (8) ◽  
pp. 1696-1705 ◽  
Author(s):  
Shinichiro Teramoto ◽  
Nobukazu Miyamoto ◽  
Kenji Yatomi ◽  
Yasutaka Tanaka ◽  
Hidenori Oishi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Receptor Agonist ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Vehicle Group ◽  
Intracellular Camp ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Camp Levels

Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia–reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.

Abstract W P369: Inhibitory Effect of FTY720 on Neuroinflammation in Cerebral Ischemia-reperfusion

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Haoliang Xu ◽  
Pratik Shah ◽  
Dale Pelligrino ◽  
Fernando D Testai
Keyword(s):  
Cerebral Ischemia ◽  
Water Content ◽  
Brain Edema ◽  
Leukocyte Adhesion ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Therapeutic Window ◽  
Vehicle Group ◽  
Leukocyte Trafficking ◽  
Cerebral Ischemia Reperfusion

Background: Neuroinflammation is a key contributor to brain injury in cerebral ischemia-reperfusion (CIR). FTY720 has been shown to be neuroprotective in animal stroke models. In most studies, FTY720 treatment was initiated either before or shortly after the cerebral insult. The goal of this study is to investigate the effect of FTY720 on CIR-associated neuroinflammation and outcome using a therapeutic window similar to the one utilized in clinical practice. Methods: We used the rat middle cerebral artery (MCA) occlusion model for CIR. The right MCA was occluded for 1h followed by reperfusion. Animals were treated with vehicle or 0.5 mg/kg FTY720 intraperitoneally at 3h post-reperfusion. Neurobehavioral test battery (scale from 0 to 21 points with lower scores representing increased neurological deficits), grid-walking test, infarct volume, and brain water content were determined 24h post CIR. A cranial window was established at 24h post occlusion and leukocyte trafficking behavior was monitored by direct microscopic observation of surface venules. Pial venular leukocyte adhesion was expressed as the % of vascular area occupied by adherent rhodamine-6G-labeled leukocytes. Statistical analysis was performed by t test. Results: Compared to the vehicle group (n=10), FTY720 animals (n=10) had improved neurological score (8.6±1.9 vs. 13.7±1.9; p<0.001) and better motor performance throughout all subsections of the grid test (p<0.001). FTY720 treatment also decreased infarct volume (vehicle: 342±182; FTY720: 122±138 mm 3 ; p=0.04) and ipsilateral brain edema, measured as water content (vehicle: 84.5±1.05%; FTY720: 79.4±0.87%, p=0.003). Leukocyte trafficking study showed a significant increase in vascular leukocyte adhesion 24 h post reperfusion in the vehicle group which was markedly decreased by FTY720 treatment (sham: 3.0±0.6%; vehicle: 11.4±2.6%; FTY720: 5.2±1.4%; p<0.001). Conclusion: FTY720 given at 3h post reperfusion reduces infarct volume, brain edema, neurological disability, and vascular leukocyte adhesion. These results support the beneficial effect of FTY720 when used in a clinically relevant timeframe and provides direct evidence of the anti-inflammatory effect of FTY720 on CIR.

scholarly journals Neuroprotective Effect of DAHP via Antiapoptosis in Cerebral Ischemia

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yanhua Qin ◽  
Weiming Hu ◽  
Yang Yang ◽  
Zhiying Hu ◽  
Weiyun Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Caspase 3 ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Tunel Staining ◽  
Cox 2

Aberrant production of nitric oxide following inducible nitric oxide synthase (iNOS) expression has been implicated in cell death and contributes to ischemic brain injury. Tetrahydrobiopterin (BH4) is an essential cofactor of NOS activity. Herein, we evaluated antiapoptotic and anti-inflammatory effects of diamino-6-hydroxypyrimidine (DAHP), a guanosine 5′-triphosphate cyclohydrolase 1 (GTPCH1) inhibitor on focal cerebral ischemia-reperfusion injury by middle cerebral artery occlusion and reperfusion (MCAO) and investigated the underlying mechanism. Sprague-Dawley rats were divided into five groups. Experimental groups were subjected to 1.5 h transient MCAO. T2-weighted imaging was performed to evaluate brain edema lesions in the stroke rats. Infarct volume was estimated by 2,3,5-triphenyltetrazolium chloride (TTC) staining after 24 h reperfusion. Western blotting and immunohistochemistry were performed to detect iNOS, caspase-3, Bcl-2, COX-2, and TNF-α protein expressions. Apoptosis was determined by TUNEL staining. T2 hyperintensity changes were observed in primary ischemic region. DAHP pretreatment significantly suppressed iNOS overexpression, caspase-3, and TNF-α. There was also attenuation of neuronal apoptosis with decrement in proteins Bcl-2 and COX-2 expressions. On the basis of our results, we hypothesize DAHP to have a neuroprotective function against focal cerebral ischemia and might attenuate brain injury by decreasing reactive oxygen species (ROS) production, subsequently inhibiting apoptosis.

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 Rapamycin Pretreatment Alleviates Cerebral Ischemia/Reperfusion Injury in Dose-Response Manner Through Inhibition of the Autophagy and NFκB Pathways in Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094619
Author(s):  
Liru Li ◽  
Jie Huang
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Vehicle Group ◽  
Sprague Dawley ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion ◽  
Y Maze

Although rapamycin can attenuate cerebral ischemia/reperfusion (I/R) injury, the potential roles of rapamycin on cerebral I/R injury remain largely controversial. The present work aims to evaluate underlying molecular mechanisms of rapamycin pretreatment on I/R injury. In total, 34 Sprague-Dawley rats were randomly grouped to 3 groups: sham group (n = 2), vehicle group (n = 16), and rapamycin-pretreatment group (n = 16). Before the focal cerebral ischemia was induced, those rats in the pretreatment group were intraperitoneally injected rapamycin (1 mg/kg body) for 20 hours, while rats in the vehicle group received same-volume saline. Then, rats in these 2 groups received focal cerebral ischemia for 3 and 6 hours, respectively (n = 8 in each group), which was followed by the application of reperfusion for 4, 24, 72 hours, and 1 week (n = 2 in each group). The results showed that the rapamycin pretreatment improved the memory functions of rats after I/R injury, which was evaluated using a Y-maze test. Rapamycin pretreatment significantly reduced the size of triphenyltetrazolium chloride infarction and decreased the expression of I/R injury markers. Moreover, the expression of LC-3 and NFκB was also significantly reduced after rapamycin pretreatment. Taken together, rapamycin pretreatment may alleviate cerebral I/R injury partly through inhibiting autophagic activities and NFκB pathways in rats.

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