scholarly journals Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats

2022 ◽  
Vol 66 (1) ◽  
Author(s):  
Zhen Wang ◽  
Xiaoyan Du ◽  
Daoyang Yu ◽  
Yang Yang ◽  
Gaoen Ma ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Brain Tissue ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Collagen Iv ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Stroke is a brain system disease with a high fatality rate and disability rate. About 80% of strokes are ischemic strokes. Cerebral ischemia-reperfusion injury (CIRI) caused by ischemic stroke seriously affects the prognosis of stroke patients. The purpose of this study is to investigate the effect of sufentanil (SUF) on CIRI model rats. We used middle cerebral artery occlusion (MCAO) to make the CIRI model in rats and monitored region cerebral blood flow (rCBF) to ensure that blood flow was blocked and recanalized. We used ELISA and RT-PCR to detect the expression of inflammatory factors in rat serum and brain tissue. In addition, we detected the expression of metalloproteinase (MMP) 2, MMP9 and collagen IV in brain tissues and performed Evans blue (EB) assay to determine the permeability of the blood-brain barrier (BBB). Finally, we clarified the apoptosis of brain tissue through the TUNEL staining and the detection of caspase3, Bcl2 and Bax. Various concentrations of SUF, especially 5, 10 and 25 μg/kg of SUF, all alleviated the infarct size, neurological function and brain edema of MCAO rats. SUF pretreatment also effectively reduced the expression of inflammatory cytokines in MCAO rats, including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α. In addition, SUF also inhibited MMP2 and MMP9 and promoted the expression of collagen IV, indicating that SUF attenuated the destruction of the BBB. SUF also inhibited caspase3 and Bax rats and promoted Bcl2 in MCAO rats, thus inhibiting cell apoptosis. SUF pretreatment effectively improved the neurological function and cerebral infarction of MCAO rats, inhibited excessive inflammation in rats, protected the BBB, and inhibited cell apoptosis in brain tissue.

Abstract 2473: Ubiquitin Ligase Huwe1 Modulates Prongf/p75ntr In Monkey Cerebral Ischemia-reperfusion Injury

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Qian G He ◽  
Lihua Yu ◽  
Wenming Xu ◽  
Jiachuan Duan ◽  
Jian Guo ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ubiquitin Ligase ◽  
Cell Apoptosis ◽  
Sham Group ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Model Group ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Background: Ischemic neuronal cell apoptosis is a principal neuropathological feature of stroke. The p75 neurotrophin receptor (p75NTR) induces apoptosis associated with JNK-p53-BAX pathway, p53 is the substrate of the HECT domain-containing E3 ubiquitin ligase Huwe1. Recent studies suggest that the precursor form of NGF (proNGF) binds to p75NTR, and withhold the interaction of proNGF/p75NTR is efficacious in reducing neuronal apoptosis. Studies on tumor and phylogeny, show that Huwe1 highly expressed in CNS, playing a role in the regulation of cell apoptosis and a variety of injury types. Our aim is to examine whether Huwe1 modulates proNGF/p75NTR in cerebral ischemia-reperfusion injury. Methods: Eight male rhesus monkey were randomly divided into two groups: sham(n=2) and model group(n=6). The model group was administered equal volume of PBS, or silencing huwe1 Lentiviral Vector or empty Vector in right caudatum and putamen using brain stereotaxic technology and subjected to transient right middle cerebral artery occlusion (MCAO) a month later. A battery of neurological evaluation and magnetic resonance imaging (MRI) were employed to evaluate animals. Animals were sacrificed 3 days after MCAO and brains were processed for testing transfection efficiency using GFP fluorescence and evaluating cell apoptosis using TUNEL staining. The related factors in caudatum, putamen, temporal lobe and hippocampus was analyzed with QPCR, western blotting with loading control GADPH, and Immunohistochemistry. Results: The model group showed significant functional deficit than sham group with neurological evaluation (p<0.05), whereas the silencing Huwe1 group’s was the most serious. In right caudatum and putament, ischemia-reperfusion injury increased the number of TUNEL+cells(p<0.05 vs sham group) and upregulation of huwe1, proNGF and p75NTR in protein and nucleotides level (p<0.05 vs sham group), but silencing Huwe1 group increased TUNEL+cells most significantly, produced profound modulation with decreased expression of Huwe1 and obvious upregulation of proNGF and p75NTR(p<0.05 vs PBS or empty Vector group) ( Figure 1 ). However, there is no significant difference in other positions (data not show). Conclusions: Huwe1 modulates proNGF/p75NTR in the cerebral ischemia-reperfusion injury, and p53 may be as a indirect fator involved in this process. Our findings provide a novel mechanism in regulating proNGF/p75NTR signaling, suggesting its potential therapeutic target in ischemic stroke.

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