The Neuroprotection of 1,2,4‐Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke
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| Formato: | Artículo Open Access |
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Wiley
2024
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| _version_ | 1867002333110468608 |
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| author | Xuan Liu Jingning Luo Jianwen Chen Ping Huang Gongyun He Xueshi Ye Ruiqi Su Yaoqiang Lao Yang Wang Xiangjun He Jingxia Zhang |
| author_facet | Xuan Liu Jingning Luo Jianwen Chen Ping Huang Gongyun He Xueshi Ye Ruiqi Su Yaoqiang Lao Yang Wang Xiangjun He Jingxia Zhang Xuan Liu Jingning Luo Jianwen Chen Ping Huang Gongyun He Xueshi Ye Ruiqi Su Yaoqiang Lao Yang Wang Xiangjun He Jingxia Zhang |
| collection | Wiley Open Access |
| contents | The Neuroprotection of 1,2,4‐Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke Xuan Liu Jingning Luo Jianwen Chen Ping Huang Gongyun He Xueshi Ye Ruiqi Su Yaoqiang Lao Yang Wang Xiangjun He Jingxia Zhang CNS Neuroscience & Therapeutics ABSTRACTBackgroundThe 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.AimIn this study, we continue to investigate its neuroprotection by anti‐inflammatory effects and protecting BBB integrity in AIS.Methods and ResultsFirst, 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.ConclusionBased on these findings, SYS18 has a strong potential to become a neuroprotectant in the future. 10.1111/cns.70113 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1111/cns.70113 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_cns_70113 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | The Neuroprotection of 1,2,4‐Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke Xuan Liu Jingning Luo Jianwen Chen Ping Huang Gongyun He Xueshi Ye Ruiqi Su Yaoqiang Lao Yang Wang Xiangjun He Jingxia Zhang CNS Neuroscience & Therapeutics The Neuroprotection of 1,2,4‐Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke Xuan Liu Jingning Luo Jianwen Chen Ping Huang Gongyun He Xueshi Ye Ruiqi Su Yaoqiang Lao Yang Wang Xiangjun He Jingxia Zhang CNS Neuroscience & Therapeutics ABSTRACTBackgroundThe 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.AimIn this study, we continue to investigate its neuroprotection by anti‐inflammatory effects and protecting BBB integrity in AIS.Methods and ResultsFirst, 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.ConclusionBased on these findings, SYS18 has a strong potential to become a neuroprotectant in the future. 10.1111/cns.70113 http://creativecommons.org/licenses/by/4.0/ |
| title | The Neuroprotection of 1,2,4‐Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke |
| topic | CNS Neuroscience & Therapeutics |
| url | https://onlinelibrary.wiley.com/doi/10.1111/cns.70113 |