Role of xanthine dehydrogenase and oxidase in focal cerebral ischemic injury to rat

1991 ◽  
Vol 261 (6) ◽  
pp. H2051-H2057 ◽  
Author(s):  
S. Lindsay ◽  
T. H. Liu ◽  
J. A. Xu ◽  
P. A. Marshall ◽  
J. K. Thompson ◽  
...  
Keyword(s):  
Free Radical ◽  
Xanthine Oxidase ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Primary Source ◽  
Ischemic Injury ◽  
Xanthine Dehydrogenase ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

The role of xanthine dehydrogenase and oxidase as a source of free radicals contributing to focal cerebral ischemic injury was evaluated in Long-Evans rats after the middle cerebral artery was permanently occluded and both carotid arteries were clamped for 90 min. The fraction of xanthine dehydrogenase present as the free radical producing oxidase increased slightly from 22% in control cortex to 30% in the ischemic right cortex during the first 3 h of reperfusion and then remained relatively unchanged over the next 24 h. This increase may in part be due to entrapped plasma, which contained 4.5 +/- 0.8 nmol.min-1.ml-1 xanthine oxidase entirely in the free radical-producing form. Infarct volume was unaffected by pretreatment with 50 mg allopurinol/kg per day over 3 days before surgery but was decreased by 8% with 100 mg/kg and 24% with 150 mg/kg of allopurinol (P less than 0.05). However, inhibition of xanthine oxidase by dietary depletion of the essential molybdenum cofactor increased infarct volume by 19%, suggesting that protection by allopurinol at higher dosages was independent of xanthine oxidase inhibition. Neither xanthine oxidase present in rat brain nor circulating in plasma appears to be the primary source of oxygen radicals that contributes to infarction in focal cerebral ischemia.

scholarly journals Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Zun-Jing Liu ◽  
Wei Liu ◽  
Lei Liu ◽  
Cheng Xiao ◽  
Yu Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Infarct Volume ◽  
Critical Role ◽  
Ischemic Injury ◽  
Ppar Gamma ◽  
Neurological Deficits ◽  
Protective Effects ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγagonist in that it upregulated PPARγexpression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγinteracted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγinduced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

Role of the neurovascular unit in the process of cerebral ischemic injury

2020 ◽  
Vol 160 ◽  
pp. 105103 ◽  
Author(s):  
Yu Zhao ◽  
Jiehong Yang ◽  
Chang Li ◽  
Guoying Zhou ◽  
Haofang Wan ◽  
...  
Keyword(s):  
Neurovascular Unit ◽  
Ischemic Injury ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

miR-137 alleviates focal cerebral ischemic injury in rats by regulating JAK1/STAT1 signaling pathway

2020 ◽  
Vol 39 (6) ◽  
pp. 816-827
Author(s):  
M Zhang ◽  
DJ Ge ◽  
Z Su ◽  
B Qi
Keyword(s):  
Brain Tissue ◽  
Hippocampal Neurons ◽  
Focal Cerebral Ischemia ◽  
Cell Damage ◽  
Ischemic Injury ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

The repairing effect and potential mechanism of miR-137 on cerebral ischemic injury in rats was investigated. The volume of cerebral infarction and calculated brain water content was detected by triphenyltetrazolium chloride staining. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay. The pathological damage of brain tissue was analyzed by hematoxylin and eosin and Nissl staining. The apoptosis in ischemic brain tissue was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. The levels of STAT1 and JAK1 proteins were analyzed by Western blot. The expression of miR-137 in primary hippocampal neurons was detected by reverse transcription polymerase chain reaction. miR-137 overexpression significantly improved brain damage in rats. miR-137 overexpression can reduce the expression of TNF-α, IL-1β, and IL-6. miR-137 overexpression can reduce the degree of brain tissue damage and inhibit the expression of JAK1 and STAT1 proteins. miR-137 overexpression can reduce oxygen-glucose deprivation (OGD)/R-induced cell damage, improve cell proliferation, and reduce apoptotic rate. JAK1 and STAT1 protein expression was inhibited in hippocampal neurons after OGD/R treatment after transfection with miR-137 mimic. After the addition of the Filgotinib inhibitor, the levels of JAK1 and STAT1 proteins were significantly reduced. The results suggested that miR-137 overexpression can effectively improve ischemic injury after focal cerebral ischemia and protect against by inhibiting JAK1/STAT1 pathway.

The role of long non-coding RNA SNHG12 in neuroprotection following cerebral ischemic injury

Neuroreport ◽  
2019 ◽  
Vol 30 (14) ◽  
pp. 945-952
Author(s):  
Yanyong Cheng ◽  
Yunfeng Jiang ◽  
Yu Sun ◽  
Hong Jiang
Keyword(s):  
Ischemic Injury ◽  
Non Coding Rna ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Long Non Coding Rna

scholarly journals Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels

2004 ◽  
Vol 89 (5) ◽  
pp. 1283-1292 ◽  
Author(s):  
Fabienne de Bilbao ◽  
Denis Arsenijevic ◽  
Philippe Vallet ◽  
Ole Petter Hjelle ◽  
Ole Petter Ottersen ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Ischemic Injury ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Mitochondrial Glutathione

Abstract TP100: Pharmacological Inhibition of ACC1 Restrains Peripheral T Cell Activation and Protects Against Cerebral Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Peiying Li ◽  
Long Wang ◽  
Yuxi Zhou ◽  
Xing Wang ◽  
Weifeng Yu
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Infarct Volume ◽  
Ischemic Injury ◽  
Ischemic Brain ◽  
Soraphen A ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Adhesive Removal

Background and purpose: T cell activation, which is detrimental to the ischemic brain, requires metabolic reprogramming to meet the increased fuel demanding. ACC1 is an enzyme catalyzing the carboxylation of acetyl-CoA to malonyl CoA, a key substrate in the glycolytic-lipogenic pathway, which is extremely critical for T cell differentiation and phenotype polarization. We tested the hypothesis that pharmacologically inhibiting the enzyme ACC1 early after stroke may restrain T cell activation and protect against cerebral ischemic injury. Methods: Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 60 minutes in C57/B6 mice. Soraphen A, the specific pharmacological inhibitor of ACC1 was administered at 1 hour after reperfusion at the dose of 1mg/kg, 5mg/kg, 10mg/kg and 50mg/kg intraperitoneally. Infarct volume was assess at 3 days after surgery by staining with 2,3,5-triphenyltetrazolium chloride. Behavior assessments, such as body proprioception, climbing, forelimb walking, lateral turning, foot fault and adhesive removal were examined at 3, 5, 7, 14, 21 and 28 days after stroke. T cell infiltration into the ischemic brain was examined by immunofluorescent staining. Results: Mice treated with 5mg/kg or 10mg/kg soraphen A exhibited significantly smaller infarct volume at 3 days after stroke. 5mg/kg was chosen as the dose for further experiments. Soraphen A treatment improved the overall neurological assessment and enhanced the performance of mice in adhesive removal test and grid walking test. Soraphen A treatment significantly attenuated the CD3+ T cell and Gr-1+ neutrophil infiltration in the ischemic mice brain at 3 days after surgery. Conclusion: Pharmacological inhibition of T cell activation by soraphen A is protective against cerebral ischemic injury and may represent a novel strategy for stroke therapy.

scholarly journals The Role of TRPC6 in the Neuroprotection of Calycosin Against Cerebral Ischemic Injury

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Chao Guo ◽  
Yongyuan Ma ◽  
Shanbo Ma ◽  
Fei Mu ◽  
Jiao Deng ◽  
...  
Keyword(s):  
Ischemic Injury ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

scholarly journals CELSR1 Promotes Neuroprotection in Cerebral Ischemic Injury Mainly through the Wnt/PKC Signaling Pathway

2020 ◽  
Vol 21 (4) ◽  
pp. 1267 ◽  
Author(s):  
Li-Hong Wang ◽  
Geng-Lin Zhang ◽  
Xing-Yu Liu ◽  
Ai Peng ◽  
Hai-Yuan Ren ◽  
...  
Keyword(s):  
Motor Function ◽  
Cell Apoptosis ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Cerebral Artery Occlusion

Cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1) is a member of a special subgroup of adhesion G protein-coupled receptors. Although Celsr1 has been reported to be a sensitive gene for stroke, the effect of CELSR1 in ischemic stroke is still not known. Here, we investigated the effect of CELSR1 on neuroprotection, neurogenesis and angiogenesis in middle cerebral artery occlusion (MCAO) rats. The mRNA expression of Celsr1 was upregulated in the subventricular zone (SVZ), hippocampus and ischemic penumbra after cerebral ischemic injury. Knocking down the expression of Celsr1 in the SVZ with a lentivirus significantly reduced the proliferation of neuroblasts, the number of CD31-positive cells, motor function and rat survival and increased cell apoptosis and the infarct volume in MCAO rats. In addition, the expression of p-PKC in the SVZ and peri-infarct tissue was downregulated after ischemia/ reperfusion. Meanwhile, in the dentate gyrus of the hippocampus, knocking down the expression of Celsr1 significantly reduced the proliferation of neuroblasts; however, it had no influence on motor function, cell apoptosis or angiogenesis. These data indicate that CELSR1 has a neuroprotective effect on cerebral ischemia injury by reducing cell apoptosis in the peri-infarct cerebral cortex and promoting neurogenesis and angiogenesis, mainly through the Wnt/PKC pathway.

scholarly journals The Roles of High Mobility Group Box 1 in Cerebral Ischemic Injury

2020 ◽  
Vol 14 ◽  
Author(s):  
Xiaoyun Gou ◽  
Junjie Ying ◽  
Yan Yue ◽  
Xia Qiu ◽  
Peng Hu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
High Mobility ◽  
Ischemic Injury ◽  
High Mobility Group ◽  
Cellular Functions ◽  
Surface Receptors ◽  
Hypoxic Ischemia ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that plays an important role in stabilizing nucleosomes and DNA repair. HMGB1 can be passively released from necrotic neurons or actively secreted by microglia, macrophages/monocytes, and neutrophils. Cerebral ischemia is a major cause of mortality and disability worldwide, and its outcome depends on the number of neurons dying due to hypoxia in the ischemic area. HMGB1 contributes to the pathogenesis of cerebral ischemia via mediating neuroinflammatory responses to cerebral ischemic injury. Extracellular HMGB1 regulates many neuroinflammatory events by interacting with its different cell surface receptors, such as receptors for advanced glycation end products, toll-like receptor (TLR)-2, and TLR-4. Additionally, HMGB1 can be redox-modified, thus exerting specific cellular functions in the ischemic brain and has different roles in the acute and late stages of cerebral ischemic injury. However, the role of HMGB1 in cerebral ischemia is complex and remains unclear. Herein, we summarize and review the research on HMGB1 in cerebral ischemia, focusing especially on the role of HMGB1 in hypoxic ischemia in the immature brain and in white matter ischemic injury. We also outline the possible mechanisms of HMGB1 in cerebral ischemia and the main strategies to inhibit HMGB1 pertaining to its potential as a novel critical molecular target in cerebral ischemic injury.

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