Xuan Liu, Jingning Luo, Jianwen Chen, Ping Huang, Gongyun He, Xueshi Ye, Ruiqi Su, Yaoqiang Lao, Yang Wang, Xiangjun He, Jingxia Zhang
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Then, the MCAO cerebral edema models were built to evaluate its neuroprotection by reducing the neurological score, cerebral edema, improving the biochemical indicators, and pathological damage of brain tissue. At the same time, its protection on blood–brain barrier (BBB) integrity was proved by decreasing the BBB permeability and inhibiting glycocalyx degradation and regulating the BBB tight junction proteins expression of matrix metalloproteinase- 9 (MMP- 9) and claudin- 5 in brain tissue. Meanwhile, pharmacokinetic experiments showed that the compound had good BBB penetration. It has some advantages in the intensity of efficacy compared with the marketed drug edaravone.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Based on these findings, SYS18 has a strong potential to become a neuroprotectant in the future.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537802/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Neuroprotection of 1,2,4-Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke\",\"authors\":\"Xuan Liu, Jingning Luo, Jianwen Chen, Ping Huang, Gongyun He, Xueshi Ye, Ruiqi Su, Yaoqiang Lao, Yang Wang, Xiangjun He, Jingxia Zhang\",\"doi\":\"10.1111/cns.70113\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>The oxidative stress and neuroinflammation are important factors in acute ischemic stroke (AIS). 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The Neuroprotection of 1,2,4-Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke
Background
The oxidative stress and neuroinflammation are important factors in acute ischemic stroke (AIS). Our former study showed the 1,2,4- triazole derivative (SYS18) had obviously neuroprotection by anti- oxidative stress on rat middle cerebral artery occlusion (MCAO) model.
Aim
In this study, we continue to investigate its neuroprotection by anti-inflammatory effects and protecting BBB integrity in AIS.
Methods and Results
First, its effect on acute inflammation was evaluated by the mice model of increased peritoneal capillary permeability. Then, the MCAO cerebral edema models were built to evaluate its neuroprotection by reducing the neurological score, cerebral edema, improving the biochemical indicators, and pathological damage of brain tissue. At the same time, its protection on blood–brain barrier (BBB) integrity was proved by decreasing the BBB permeability and inhibiting glycocalyx degradation and regulating the BBB tight junction proteins expression of matrix metalloproteinase- 9 (MMP- 9) and claudin- 5 in brain tissue. Meanwhile, pharmacokinetic experiments showed that the compound had good BBB penetration. It has some advantages in the intensity of efficacy compared with the marketed drug edaravone.
Conclusion
Based on these findings, SYS18 has a strong potential to become a neuroprotectant in the future.
期刊介绍：
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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