{"title":"异丙酚通过阻断TLR4通路改善小鼠缺血性脑损伤。","authors":"Kazuha Mitsui, Masakazu Kotoda, Sohei Hishiyama, Ayasa Takamino, Sho Morikawa, Tadahiko Ishiyama, Takashi Matsukawa","doi":"10.1515/tnsci-2022-0238","DOIUrl":null,"url":null,"abstract":"<p><p>Ischemic brain injury is one of the most serious perioperative complications. However, effective preventative methods have not yet been established. This study aimed to investigate whether propofol has neuroprotective effects against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4). Focal brain ischemia was induced via a combination of left common carotid artery occlusion and distal left middle cerebral artery coagulation in mice. Either propofol (10 mg/kg) or vehicle was intravenously injected 10 min prior to the induction of brain ischemia in wild-type and TLR4 knockout mice. Infarct volume, pro-inflammatory cytokine expression, inflammatory cell infiltration, and neurobehavioral function were assessed. Propofol administration significantly reduced infarct volume in wild-type mice (26.9 ± 2.7 vs 15.7 ± 2.0 mm<sup>3</sup> at day 7), but not in TLR4 knockout mice. Compared with the control mice, the propofol-treated wild-type mice exhibited lower levels of IL-6 (0.57 ± 0.23 vs 1.00 ± 0.39 at 24 h), and smaller numbers of TLR4-expressing microglia in the penumbra (11.7 ± 3.1 vs 25.1 ± 4.7 cells/0.1 mm<sup>2</sup>). In conclusion, propofol administration prior to ischemic brain insult attenuated brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438965/pdf/","citationCount":"0","resultStr":"{\"title\":\"Propofol ameliorates ischemic brain injury by blocking TLR4 pathway in mice.\",\"authors\":\"Kazuha Mitsui, Masakazu Kotoda, Sohei Hishiyama, Ayasa Takamino, Sho Morikawa, Tadahiko Ishiyama, Takashi Matsukawa\",\"doi\":\"10.1515/tnsci-2022-0238\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ischemic brain injury is one of the most serious perioperative complications. However, effective preventative methods have not yet been established. This study aimed to investigate whether propofol has neuroprotective effects against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4). Focal brain ischemia was induced via a combination of left common carotid artery occlusion and distal left middle cerebral artery coagulation in mice. Either propofol (10 mg/kg) or vehicle was intravenously injected 10 min prior to the induction of brain ischemia in wild-type and TLR4 knockout mice. Infarct volume, pro-inflammatory cytokine expression, inflammatory cell infiltration, and neurobehavioral function were assessed. Propofol administration significantly reduced infarct volume in wild-type mice (26.9 ± 2.7 vs 15.7 ± 2.0 mm<sup>3</sup> at day 7), but not in TLR4 knockout mice. Compared with the control mice, the propofol-treated wild-type mice exhibited lower levels of IL-6 (0.57 ± 0.23 vs 1.00 ± 0.39 at 24 h), and smaller numbers of TLR4-expressing microglia in the penumbra (11.7 ± 3.1 vs 25.1 ± 4.7 cells/0.1 mm<sup>2</sup>). In conclusion, propofol administration prior to ischemic brain insult attenuated brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production.</p>\",\"PeriodicalId\":23227,\"journal\":{\"name\":\"Translational Neuroscience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2022-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438965/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1515/tnsci-2022-0238\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1515/tnsci-2022-0238","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
缺血性脑损伤是围手术期最严重的并发症之一。然而,有效的预防方法尚未确立。本研究旨在探讨异丙酚是否对缺血性脑损伤具有神经保护作用,并特别关注toll样受体4 (TLR4)。采用左颈总动脉闭塞联合左大脑中远端动脉凝固的方法诱导小鼠局灶性脑缺血。在野生型和TLR4基因敲除小鼠脑缺血诱导前10分钟静脉注射异丙酚(10 mg/kg)或对照物。评估梗死体积、促炎细胞因子表达、炎症细胞浸润和神经行为功能。异丙酚可显著减少野生型小鼠的梗死体积(第7天26.9±2.7 vs 15.7±2.0 mm3),但在TLR4敲除小鼠中没有。与对照组相比,异丙酚野生型小鼠IL-6水平较低(24 h时为0.57±0.23 vs 1.00±0.39),半暗带表达tlr4的小胶质细胞数量较少(11.7±3.1 vs 25.1±4.7细胞/0.1 mm2)。结论:缺血性脑损伤前异丙酚通过阻断tlr4依赖通路和抑制促炎细胞因子的产生来减轻脑损伤。
Propofol ameliorates ischemic brain injury by blocking TLR4 pathway in mice.
Ischemic brain injury is one of the most serious perioperative complications. However, effective preventative methods have not yet been established. This study aimed to investigate whether propofol has neuroprotective effects against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4). Focal brain ischemia was induced via a combination of left common carotid artery occlusion and distal left middle cerebral artery coagulation in mice. Either propofol (10 mg/kg) or vehicle was intravenously injected 10 min prior to the induction of brain ischemia in wild-type and TLR4 knockout mice. Infarct volume, pro-inflammatory cytokine expression, inflammatory cell infiltration, and neurobehavioral function were assessed. Propofol administration significantly reduced infarct volume in wild-type mice (26.9 ± 2.7 vs 15.7 ± 2.0 mm3 at day 7), but not in TLR4 knockout mice. Compared with the control mice, the propofol-treated wild-type mice exhibited lower levels of IL-6 (0.57 ± 0.23 vs 1.00 ± 0.39 at 24 h), and smaller numbers of TLR4-expressing microglia in the penumbra (11.7 ± 3.1 vs 25.1 ± 4.7 cells/0.1 mm2). In conclusion, propofol administration prior to ischemic brain insult attenuated brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production.
期刊介绍:
Translational Neuroscience provides a closer interaction between basic and clinical neuroscientists to expand understanding of brain structure, function and disease, and translate this knowledge into clinical applications and novel therapies of nervous system disorders.