Propagermanium, a CCR2 inhibitor, attenuates cerebral ischemia/reperfusion injury through inhibiting inflammatory response induced by microglia

2019 ◽  
Vol 125 ◽  
pp. 99-110 ◽  
Author(s):  
Shucheng He ◽  
Rui Liu ◽  
Binbin Li ◽  
Liangliang Huang ◽  
Wenxiang Fan ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

scholarly journals Tibetan Medicine Qishiwei Zhenzhu Pills Can Reduce Cerebral Ischemia-Reperfusion Injury by Regulating Gut Microbiota and Inhibiting Inflammation

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ke Fu ◽  
Dewei Zhang ◽  
Yinglian Song ◽  
Min Xu ◽  
Ruixia Wu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Cerebral Infarction ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tibetan Medicine ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Cerebral ischemia is a series of harmful reactions, such as acute necrosis of tissue, inflammation, apoptosis, autophagy, and blood-brain barrier injury, due to the insufficient blood supply to the brain. Inflammatory response and gut microbiota imbalance are important concomitant factors of cerebral ischemia and may increase the severity of cerebral ischemia through the gut-brain axis. Qishiwei Zhenzhu pills (QSW) contain more than 70 kinds of medicinal materials, which have the effects of anti-cerebral infarction, anti-convulsion, anti-dementia, and so on. It is a treasure of Tibetan medicine commonly used in the treatment of cerebral ischemia in Tibetan areas. In this study, we gave rats QSW (66.68 mg/kg) once by gavage in advance and then immediately established the rat middle cerebral artery occlusion (MCAO) model. After 24 hours of treatment, the neuroprotection, intestinal pathology, and gut microbiota were examined. The results showed that QSW could significantly reduce the neurobehavioral abnormalities and cerebral infarction rate in MCAO rats. Furthermore, qPCR, western blot, and immunohistochemistry results showed that QSW could effectively inhibit IL-6, IL-1β, and other inflammatory factors so as to effectively reduce the inflammatory response of MCAO rats. Furthermore, QSW could improve intestinal integrity and reduce intestinal injury. 16S rRNA sequencing showed that QSW could significantly improve the gut microbiota disorder of MCAO rats. Specifically, at the phylum level, it can regulate the abundance of Firmicutes and Proteobacteria in the gut microbiota of rats with MCAO. At the genus level, it can adjust the abundance of Escherichia and Shigella. At the species level, it can adjust the abundance of Lactobacillus johnsonii and Lactobacillus reuteri. All in all, this study is the first to show that QSW can reduce the severity of cerebral ischemia-reperfusion injury by regulating gut microbiota and inhibiting the inflammatory response.

scholarly journals Neuroprotection in Ischemia–Reperfusion Injury: An Antiinflammatory Approach Using a Novel Broad-Spectrum Chemokine Inhibitor

2001 ◽  
Vol 21 (6) ◽  
pp. 683-689 ◽  
Author(s):  
John S. Beech ◽  
Jill Reckless ◽  
David E. Mosedale ◽  
David J. Grainger ◽  
Steve C. R. Williams ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Inflammatory Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lesion Volume ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Cerebral ischemia–reperfusion injury is associated with a developing inflammatory response with pathologic contributions from vascular leukocytes and endogenous microglia. Signaling chemokines orchestrate the communication between the different inflammatory cell types and the damaged tissue leading to cellular chemotaxis and lesion occupation. Several therapies aimed at preventing this inflammatory response have demonstrated neuroprotective efficacy in experimental models of stroke, but to date, few investigators have used the chemokines as potential therapeutic targets. In the current study, the authors investigate the neuroprotective action of NR58–3.14.3, a novel broad-spectrum inhibitor of chemokine function (both CXC and CC types), in a rat model of cerebral ischemia–reperfusion injury. Rats were subjected to 90 minutes of focal ischemia by the filament method followed by 72 hours of reperfusion. Both the lesion volume, measured by serial magnetic resonance imaging, and the neurologic function were assessed daily. Intravenous NR58–3.14.3 was administered, 2 mg/kg bolus followed by 0.5 mg/kg · hour constant infusion for the entire 72-hour period. At 72 hours, the cerebral leukocytic infiltrate, tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8)-like cytokines were analyzed by quantitative immunofluorescence. NR58–3.14.3 significantly reduced the lesion volume by up to 50% at 24, 48, and 72 hours post–middle cerebral artery occlusion, which was associated with a marked functional improvement to 48 hours. In NR58–3.14.3-treated rats, the number of infiltrating granulocytes and macrophages within perilesional regions were reduced, but there were no detectable differences in inflammatory cell numbers within core ischemic areas. The authors reported increased expression of the cytokines, TNF-α, and IL-8–like cytokines within the ischemic lesion, but no differences between the NR58–3.14.3-treated rats and controls were reported. Although chemokines can have pro-or antiinflammatory action, these data suggest the overall effect of chemokine up-regulation and expression in ischemia–reperfusion injury is detrimental to outcome.

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