Vortioxetine mitigates neuronal damage by restricting PERK/eIF2α/ATF4/CHOP signaling pathway in rats subjected to focal cerebral ischemia-reperfusion

Life Sciences ◽  
2021 ◽  
pp. 119865
Author(s):  
Amr M. Emam ◽  
Muhammad A. Saad ◽  
Naglaa A. Ahmed ◽  
Hala F. Zaki
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion

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 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.

scholarly journals Electroacupuncture Could Regulate the NF-κB Signaling Pathway to Ameliorate the Inflammatory Injury in Focal Cerebral Ischemia/Reperfusion Model Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Wen-yi Qin ◽  
Yong Luo ◽  
Ling Chen ◽  
Tao Tao ◽  
Yang Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Inflammatory Injury ◽  
Cerebral Ischemia Reperfusion

The activated nuclear factor-KappaB signaling pathway plays a critical role in inducing inflammatory injury. It has been reported that electroacupuncture could be an effective anti-inflammatory treatment. We aimed to explore the complex mechanism by which EA inhibits the activation of the NF-κB signal pathway and ameliorate inflammatory injury in the short term; the effects of NEMO Binding Domain peptide for this purpose were compared. Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 hrs. Total 380 male Sprague-Dawley rats are in the study. The neurobehavioral scores, infarction volumes, and the levels of IL-1βand IL-13 were detected. NF-κB p65, IκBα, IKKα, and IKKβwere analyzed and the ability of NF-κB binding DNA was investigated. The EA treatment and the NBD peptide treatment both reduced infarct size, improved neurological scores, and regulated the levels of IL-1βand IL-13. The treatment reduced the expression of IKKαand IKKβand altered the expression of NF-κB p65 and IκBαin the cytoplasm and nucleus; the activity of NF-κB was effectively reduced. We conclude that EA treatment might interfere with the process of NF-κB nuclear translocation. And it also could suppress the activity of NF-κB signaling pathway to ameliorate the inflammatory injury after focal cerebral ischemia/reperfusion.

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