scholarly journals Neuroprotection of Sanhua Decoction against Focal Cerebral Ischemia/Reperfusion Injury in Rats through a Mechanism Targeting Aquaporin 4

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Lin Lu ◽  
Hui-qin Li ◽  
Ji-huang Li ◽  
Ai-ju Liu ◽  
Guo-qing Zheng
Keyword(s):  
Cerebral Ischemia ◽  
Water Content ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Aquaporin 4 ◽  
Brain Water Content ◽  
Aqp4 Expression ◽  
Cerebral Ischemia Reperfusion ◽  
Brain Water

Sanhua decoction (SHD) is a famous classic Chinese herbal prescription for ischemic stroke, and aquaporin 4 (AQP4) is reported to play a key role in ischemic brain edema. This study aimed to investigate neuroprotection of SHD against focal cerebral ischemia/reperfusion (I/R) injury in rats and explore the hypothesis that AQP4 probably is the target of SHD neuroprotection against I/R rats. Lentiviral-mediated AQP4-siRNA was inducted into adult male Sprague-Dawley rats via intracerebroventricular injection. The focal cerebral ischemia/reperfusion model was established by occluding middle cerebral artery. Neurological examinations were performed according to Longa Scale. Brain water content, was determined by wet and dry weight measurement. Western blot was adopted to test the AQP4 expression in ipsilateral hippocampus. After the treatment, SHD alleviated neurological deficits, reduced brain water content and downregulated the expression of AQP4 at different time points following I/R injury. Furthermore, neurobehavioral function and brain edema after I/R were significantly attenuated via downregulation of AQP4 expression when combined with AQP4-siRNA technology. In conclusion, SHD exerted neuroprotection against focal cerebral I/R injury in rats mainly through a mechanism targeting AQP4.

scholarly journals Tea Polysaccharide (TPS) Reduces Astrocytes Apoptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation by Regulating the miR-375/SRXN1 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ying Jiang ◽  
Hongmei Sun ◽  
Zhiqi Yin ◽  
Jun Yan
Keyword(s):  
Cerebral Ischemia ◽  
Cell Viability ◽  
Water Content ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Brain Water Content ◽  
Cerebral Ischemia Reperfusion ◽  
Brain Water

Objective. To investigate the effect of tea polysaccharides (TPS) mediated by miR-375/SRXN1 axis on mice with cerebral ischemia-reperfusion injury and proliferation and apoptosis of astrocytes (AS) conducted with oxygen-glucose deprivation/reoxygenation (OGD/R). Methods. Mouse model of middle cerebral artery occlusion (MCAO) and OGD/R-induced AS injury model were established; brain obstruction volume was measured by TTC staining; dry/wet weight ratio was used for measuring brain water content; hydrogen peroxide (H2O2) content in brain tissue was measured by H2O2 assay kit; cell viability and apoptosis rate were detected by MTT assay and flow cytometry, respectively; the expression level of miR-375 in OGD/R-AS was detected using qPCR; dual-luciferase reporter assay was used to verify the targeting relationship between miR-375 and SRXN1; mRNA levels of miR-375, SRXN1, Bcl-2, Bax, and caspase-3 were measured by qPCR; the protein levels of SRXN1, Bcl-2, Bax, and caspase-3 were measured by Western blotting. Results. The volume of cerebral obstruction, brain water content and H2O2 content in mice decreased gradually with the increase of TPS concentration. TPS treatment in vitro could effectively improve OGD/R-AS viability and reduce the apoptotic rate; overexpression of miR-375 inhibited AS viability but increased the apoptotic rate; TPS treatment resulted in a decrease in the expression of miR-375 in OGD/R-AS; MiR-375 targeted SRXN1 in AS; inhibition of miR-375 expression significantly upregulated SRXN1 levels; TPS treatment with simultaneous overexpression of SRXN1 significantly increased OGD/R-AS activity and reduced apoptosis; however, TPS treatment with simultaneous overexpression of SRXN1 and miR-375 resulted in no significant difference in cell viability and apoptosis rate compared with the control group. Conclusion. TPS reduces astrocyte injury induced by cerebral ischemia-reperfusion in mice by regulating the miR-375/SRXN1 molecular axis.

scholarly journals Quantitation of Photochemically Induced Focal Cerebral Ischemia in the Rat

1988 ◽  
Vol 8 (1) ◽  
pp. 89-95 ◽  
Author(s):  
John J. Grome ◽  
Gerlinde Gojowczyk ◽  
Wolfgang Hofmann ◽  
David I. Graham
Keyword(s):  
Cerebral Ischemia ◽  
Water Content ◽  
Rose Bengal ◽  
Tissue Damage ◽  
Focal Cerebral Ischemia ◽  
Ischemic Damage ◽  
Brain Water Content ◽  
Ischemic Insult ◽  
Ischemic Lesion ◽  
Brain Water

This study was carried out with a recently developed model of focal cerebral ischemia in the rat based on the photochemical induction of thrombotic stroke using the dye Rose Bengal. We examined the change in the volume of the lesion and brain water content, in separate groups of rats, at different times (1, 4, 24, 72, and 168 h) after the induction of the ischemic lesion. The volume of ischemic damage increased rapidly between 1 and 24 h after the ischemic insult and decreased between 24 and 168 h. The lesion at 168 h was significantly larger than that following 1 h of ischemia and similar to that obtained at 4 h, suggesting that the maximum extent of tissue damage (without the involvement of significant edema) was reached within the first 4 h in this model. The enlargement of the lesion after 4 h correlated closely with changes in brain water content.

Brain edema after intracerebral hemorrhage in rats: the role of iron overload and aquaporin 4

2009 ◽  
Vol 110 (3) ◽  
pp. 462-468 ◽  
Author(s):  
Wang Gai Qing ◽  
Yang Qi Dong ◽  
Tang Qing Ping ◽  
Li Guang Lai ◽  
Li Dong Fang ◽  
...  
Keyword(s):  
Iron Overload ◽  
Water Content ◽  
Brain Edema ◽  
Time Course ◽  
Iron Chelator ◽  
Brain Water Content ◽  
Edema Formation ◽  
Aqp4 Expression ◽  
The Right ◽  
Brain Water

Object Brain edema formation following intracerebral hemorrhage (ICH) appears to be partly related to erythrocyte lysis and hemoglobin release. An increase of brain water content was associated with an increase of brain iron, which is an erythrocyte degradation product. Expression of AQP4 is highly modified in several brain disorders, and it can play a key role in cerebral edema formation. However, the question whether AQP4 is regulated by drugs lacks reliable evidence, and the interacting roles of iron overload and AQP4 in brain edema after ICH are unknown. The goal of this study was to clarify the relationship between iron overload and AQP4 expression and to characterize the effects of the iron chelator deferoxamine (DFO) on delayed brain edema after experimental ICH. Methods A total of 144 Sprague-Dawley rats weighing between 250 and 300 g were used in this work. The animals were randomly divided into 4 groups. The ICH models (Group C) were generated by injecting 100 μl autologous blood stereotactically into the right caudate nucleus; surgical control rats (Group B) were generated in a similar fashion, by injecting 100 μl saline into the right caudate nucleus. Intervention models (Group D) were established by intraperitoneal injection of DFO into rats in the ICH group. Healthy rats (Group A) were used for normal control models. Brain water content, iron deposition, and AQP4 in perihematomal brain tissue were evaluated over the time course of the study (1, 3, 7, and 14 days) in each group. Results Iron deposition was found in the perihematomal zone as early as the 1st day after ICH, reaching a peak after 7 days and remaining at a high level thereafter for at least 14 days following ICH. Rat brain water content around the hematoma increased progressively over the time course, reached its peak at Day 3, and still was evident at Day 7 post-ICH. Immunohistochemical analysis showed that AQP4 was richly expressed over glial cell processes surrounding microvessels in the rat brain; there was upregulation of the AQP4 expression in perihematomal brain during the observation period, and it reached maximum at 3 to 7 days after ICH. The changes of brain water content were accompanied by an alteration of AQP4. The application of the iron chelator DFO significantly reduced iron overload, brain water content, and AQP4 level in the perihematomal area compared with the control group. Conclusions Iron overload and AQP4 may play a critical role in the formation of brain edema after ICH. In addition, AQP4 expression was affected by iron concentration. Importantly, treatment with DFO significantly reduced brain edema in rats and inhibited the AQP4 upregulation after ICH. Deferoxamine may be a potential therapeutic agent for treating ICH.

Protective Effect of Astragaloside on Focal Cerebral Ischemia/Reperfusion Injury in Rats

2010 ◽  
Vol 38 (03) ◽  
pp. 517-527 ◽  
Author(s):  
Yan-Yan Yin ◽  
Wei-Ping Li ◽  
Hui-Ling Gong ◽  
Fen-Fang Zhu ◽  
Wei-Zu Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Water Content ◽  
Neurological Deficit ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Content Increase ◽  
Protective Effects ◽  
Neurological Deficit Score ◽  
Cerebral Ischemia Reperfusion

This study was to observe the neurological protective effects of astragalosides (AST) on focal cerebral ischemia-reperfusion (I/R) injury in rats and to explore its possible mechanism. Male SD rats received right middle cerebral artery occlusion for 120 min and AST (40 mg/kg) was orally administered. The rats were decapitated 1, 3, 7, and 14 days after reperfusion. The neurological deficit score, infarct volume and water content of brain were measured; the activity of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and nitric oxide synthase (NOS), and the content of malondialdehyde (MDA), lactate (LD) and nitric oxide (NO) of brain tissue were detected too. The expression of inducible nitric synthase (iNOS), nerve growth factor (NGF) and tropomyosin receptor kinase A (TrkA) mRNA were measured by RT-PCR or real-time PCR. AST could significantly reduce the neurological deficit score; infract volume and water content, increase SOD and LDH activities, decrease NOS activity and MDA, LD and NO content. AST treatment could down-regulate expression of iNOS mRNA, while, NGF and TrkA mRNA were up-regulated. Our data suggest that AST have the protective effects on focal cerebral ischemia in rats at the different reperfusion time points, the mechanism may be related to the antioxidation, regulated the expressions of iNOS, NGF and TrkA mRNA.

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 Molecular mechanisms for NG-nitro-L-arginine methyl ester action against cerebral ischemia–reperfusion injury-induced blood–brain barrier dysfunction

2014 ◽  
Vol 8 (2) ◽  
pp. 173-184
Author(s):  
Hanghui Wang ◽  
Yixin Song ◽  
Dingjun Hao ◽  
Lianfang Du
Keyword(s):  
Electron Microscope ◽  
Cerebral Ischemia ◽  
Methyl Ester ◽  
Evans Blue ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Brain Water Content ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Brain Water

Abstract Background: Ischemic stroke, an acute neurological injury lacking an effective therapy, is a leading cause of death worldwide. The unmet need in stroke research is to identify viable therapeutic targets and to understand their interplay during cerebral ischemia-reperfusion (I/R) injury. Objective: To explore the protective effects and molecular mechanism of NG-nitro-L-arginine methyl ester (L-NAME) in cerebral ischemia-reperfusion injury-induced blood-brain barrier (BBB) dysfunction. Methods: Two hundred fifty-six rats were randomly assigned to a sham operation group, I/R group, and I/R with L-NAME treatment group. Brain water content was determined by calculating dry/wet weight. The permeability of the BBB was observed using an electron microscope and by determining the Evans Blue leakage from brain tissue on the ischemic side. The expression of brain MMP-9 and GFAP was determined using an immunohistochemical method. The expression of ZO-1 protein was determined by western blotting. Results: We found that L-NAME remarkably attenuated the permeability of the BBB after I/R as assessed by Evans Blue leakage and brain water content (p < 0.05). This was further confirmed by examination of the ultrastructural morphology of the BBB using a transmission electron microscope. Furthermore, we found that expression of the zonae occludens-1 (ZO-1) was decreased in endothelial cells, and expression of MMP-9 and GFAP was increased in the basement membrane and astrocyte end-feet in vehicle control groups, respectively, but these changes could be prevented by L-NAME pretreatment. Conclusion: These results suggested that the neuroprotective effects of L-NAME against BBB damage induced by I/R might be related to the upregulation of tight junction proteins and inhibition of MMP-9 and GFAP expression. L-NAME can be used as a potential MMP-9-based multiple targeting therapeutic strategy in cerebral I/R injury.

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