scholarly journals Scavenger Receptor Class-A Has a Central Role in Cerebral Ischemia–Reperfusion Injury

2010 ◽  
Vol 30 (12) ◽  
pp. 1972-1981 ◽  
Author(s):  
Chen Lu ◽  
Fang Hua ◽  
Li Liu ◽  
Tuanzhu Ha ◽  
John Kalbfleisch ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Intracellular Signaling ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Scavenger Receptor ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion

The innate immune response is involved in the pathophysiology of cerebral ischemia–reperfusion (I/R) injury. Recent evidence suggests that scavenger receptors have a role in the induction of innate immunity. In this study, we examined the role of scavenger receptor A (SR-A) in focal cerebral I/R injury. Both SR-A−/− mice ( n=10) and age-matched wild-type (WT) mice ( n=9) were subjected to focal cerebral ischemia (60 minutes), followed by reperfusion (for 24 hours). Infarct size was determined by TTC (triphenyltetrazolium chloride) staining. The morphology of neurons in the brain sections was examined by Nissl's staining. Activation of intracellular signaling was analyzed by western blot. Cerebral infarct size in SR-A−/− mice was significantly reduced by 63.9% compared with WT mice after cerebral I/R. In SR-A−/− mice, there was less neuronal damage in the hippocampus compared with WT mice. Levels of FasL, Fas, FADD, caspase-3 activity, and terminal deoynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling-positive apoptotic cells were significantly increased in WT mice after cerebral I/R, but not in SR-A−/− mice. Cerebral I/R increased nuclear factor-κB activation in WT mice, but not in SR-A−/− mice. These data suggest that SR-A has a central role in cerebral I/R injury and that suppression of SR-A may be a useful approach for ameliorating brain injury in stroke patients.

Neuroprotective Effect of Urinary Trypsin Inhibitor against Focal Cerebral Ischemia–Reperfusion Injury in Rats

2003 ◽  
Vol 98 (2) ◽  
pp. 465-473 ◽  
Author(s):  
Toshiyuki Yano ◽  
Sakiko Anraku ◽  
Ryosuke Nakayama ◽  
Kazuo Ushijima
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Trypsin Inhibitor ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Saline Control ◽  
Urinary Trypsin Inhibitor ◽  
Cerebral Ischemia Reperfusion

Background Acute inflammatory reactions cause neuronal damage in cerebral ischemia-reperfusion. Urinary trypsin inhibitor (UTI), a serine protease inhibitor, is cytoprotective against ischemia-reperfusion injury in the liver, intestine, kidney, heart, and lung through its antiinflammatory activity. Neuroprotective action of UTI on transient global cerebral ischemia has been documented. This is the first study to determine whether UTI is neuroprotective against transient focal cerebral ischemia. Methods Adult male Wistar rats were randomly assigned to the following treatment groups: 0.9% saline (control, n = 9); 100,000 U/kg UTI (n = 9); and 300,000 U/kg UTI (n = 9). Treatments were performed intravenously 10 min before right middle cerebral artery occlusion for 2 h and subsequent reperfusion. Ninety-six hours after the onset of reperfusion, the motor neurologic deficit and the cerebral infarct size were evaluated. Furthermore, immunohistochemical staining for myeloperoxidase and nitrotyrosine to count infiltrating neutrophils and nitrated cells, respectively, was performed on the brain sections. Results Infarct volume in the 300,000 U/kg UTI group was smaller than in the 100,000 U/kg UTI and saline control groups (P < 0.05). Treatment with 300,000 U/kg UTI showed a trend to improve neurologic outcome but did not reach statistical significance (P = 0.0693). The significant decrease in neutrophil infiltration was observed in the ischemic hemisphere treated with 300,000 U/kg UTI compared with saline control (P < 0.05). Nitrotyrosine deposition in the ischemic hemisphere was significantly reduced in the 300,000 U/kg UTI group compared with saline control and 100,000 U/kg UTI groups (P < 0.05). Conclusions Intravenous pretreatment with 300,000 U/kg UTI reduces focal ischemia-reperfusion injury in the rat brain, potentially opening a novel therapeutic avenue for the treatment of cerebral ischemia.

scholarly journals DJ-1 Protects against Neurodegeneration Caused by Focal Cerebral Ischemia and Reperfusion in Rats

2007 ◽  
Vol 28 (3) ◽  
pp. 563-578 ◽  
Author(s):  
Daijiro Yanagisawa ◽  
Yoshihisa Kitamura ◽  
Masatoshi Inden ◽  
Kazuyuki Takata ◽  
Takashi Taniguchi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Ischemia And Reperfusion ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia And Reperfusion

Reactive oxygen species (ROS) is massively produced in the brain after cerebral ischemia and reperfusion. It reacts strongly with cellular components, which has detrimental effects and leads to neuronal cell death. DJ-1, which was found to be the causative gene of familial Parkinson's disease PARK7, is a multifunction protein, which plays a key role in transcriptional regulation, and a molecular chaperone. In this study, we investigated the neuroprotective effect of DJ-1 against neurodegeneration caused by ischemia/reperfusion injury. Cerebral ischemia was induced in rats by 120 mins of middle cerebral artery occlusion (MCAO) using an intraluminal introduction method. The intrastriatal injection of recombinant glutathione S-transferase-tagged human DJ-1 (GST-DJ-1) markedly reduced infarct size in 2,3,5-triphenyltetrazolium chloride staining at 3 days after MCAO. In addition, we performed a noninvasive evaluation of ischemic size using magnetic resonance imaging and found a significant reduction of infarct size with the administration of GST-DJ-1. In GST-DJ-1-treated rats, behavioral dysfunction and nitrotyrosine formation were significantly inhibited. Furthermore, GST-DJ-1 markedly inhibited H2O2-mediated ROS production in SH-SY5Y cells. These results indicate that GST-DJ-1 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that DJ-1 may be a useful therapeutic target for ischemic neurodegeneration.

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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