{"title":"Dl-3-正丁基苯酞通过调节蛛网膜下腔出血后的NLRP3炎性体,减轻早期脑损伤和迟发性神经功能障碍。","authors":"Fangfang Gao , Shujin Zeng , Dachong Chao , Liangmiao Wu","doi":"10.1016/j.brainresbull.2024.111084","DOIUrl":null,"url":null,"abstract":"<div><div>Subarachnoid hemorrhage (SAH) is a severe neurological event lacking of effective therapy. Early brain injury (EBI) and delayed neurological dysfunction are important cause in the poor prognosis of patients with SAH. Nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation has been implicated in many inflammatory lesion pathogeneses including SAH. Dl-3-n-butylphthalide (NBP) has been reported to possess substantial anti-inflammatory properties, which is beneficial for various neurodegenerative diseases. However, the effect and molecular mechanisms of NBP on SAH have not been clearly identified. We designed this study to investigate the effect of NBP against EBI and delayed neurological dysfunction after SAH and to reveal the possible underlying mechanism. The adult mice were subjected to endovascular perforation SAH model or sham operation. Mice were randomized to sham group, SAH group, or SAH+NBP group. The EBI (short-term study) was studied at 48 h post-SAH and delayed neurological dysfunction (long-term study) at 21 days post-SAH. The results suggested that NBP evidently alleviated the EBI in mice at 48 h post-SAH, as shown by elevating neurological score, reducing brain edema, blood–brain barrier disruption, neuronal loss, and astrocyte aggregation, as well as ameliorating cerebral vasospasm. Moreover, NBP was able to improve long-term neurobehavioral functions and decrease neuronal apoptosis at 21 days after SAH. Significantly, NBP treatment also inhibited the expressions of NLRP3, ASC, caspase-1, cleaved-caspase-1, IL-1β, IL-18, GSDMD and GSDMD-N in both EBI and delayed neurological dysfunction induced by SAH. Our findings suggested that NBP treatment exerts a profound neuroprotective effect against early brain injury and delayed neurological dysfunction induced by SAH, at least partially through regulating NLRP3 inflammasome signaling pathway and its related inflammation and pyroptosis,</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"217 ","pages":"Article 111084"},"PeriodicalIF":3.5000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024002181/pdfft?md5=cdcf36de51801cfaa0d0c81e96f22db4&pid=1-s2.0-S0361923024002181-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Dl-3-n-Butylphthalide attenuates early brain injury and delayed neurological dysfunction by regulating NLRP3 inflammasome after subarachnoid hemorrhage\",\"authors\":\"Fangfang Gao , Shujin Zeng , Dachong Chao , Liangmiao Wu\",\"doi\":\"10.1016/j.brainresbull.2024.111084\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Subarachnoid hemorrhage (SAH) is a severe neurological event lacking of effective therapy. Early brain injury (EBI) and delayed neurological dysfunction are important cause in the poor prognosis of patients with SAH. Nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation has been implicated in many inflammatory lesion pathogeneses including SAH. Dl-3-n-butylphthalide (NBP) has been reported to possess substantial anti-inflammatory properties, which is beneficial for various neurodegenerative diseases. However, the effect and molecular mechanisms of NBP on SAH have not been clearly identified. We designed this study to investigate the effect of NBP against EBI and delayed neurological dysfunction after SAH and to reveal the possible underlying mechanism. The adult mice were subjected to endovascular perforation SAH model or sham operation. Mice were randomized to sham group, SAH group, or SAH+NBP group. The EBI (short-term study) was studied at 48 h post-SAH and delayed neurological dysfunction (long-term study) at 21 days post-SAH. The results suggested that NBP evidently alleviated the EBI in mice at 48 h post-SAH, as shown by elevating neurological score, reducing brain edema, blood–brain barrier disruption, neuronal loss, and astrocyte aggregation, as well as ameliorating cerebral vasospasm. Moreover, NBP was able to improve long-term neurobehavioral functions and decrease neuronal apoptosis at 21 days after SAH. Significantly, NBP treatment also inhibited the expressions of NLRP3, ASC, caspase-1, cleaved-caspase-1, IL-1β, IL-18, GSDMD and GSDMD-N in both EBI and delayed neurological dysfunction induced by SAH. Our findings suggested that NBP treatment exerts a profound neuroprotective effect against early brain injury and delayed neurological dysfunction induced by SAH, at least partially through regulating NLRP3 inflammasome signaling pathway and its related inflammation and pyroptosis,</div></div>\",\"PeriodicalId\":9302,\"journal\":{\"name\":\"Brain Research Bulletin\",\"volume\":\"217 \",\"pages\":\"Article 111084\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0361923024002181/pdfft?md5=cdcf36de51801cfaa0d0c81e96f22db4&pid=1-s2.0-S0361923024002181-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain Research Bulletin\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0361923024002181\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Research Bulletin","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0361923024002181","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Dl-3-n-Butylphthalide attenuates early brain injury and delayed neurological dysfunction by regulating NLRP3 inflammasome after subarachnoid hemorrhage
Subarachnoid hemorrhage (SAH) is a severe neurological event lacking of effective therapy. Early brain injury (EBI) and delayed neurological dysfunction are important cause in the poor prognosis of patients with SAH. Nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation has been implicated in many inflammatory lesion pathogeneses including SAH. Dl-3-n-butylphthalide (NBP) has been reported to possess substantial anti-inflammatory properties, which is beneficial for various neurodegenerative diseases. However, the effect and molecular mechanisms of NBP on SAH have not been clearly identified. We designed this study to investigate the effect of NBP against EBI and delayed neurological dysfunction after SAH and to reveal the possible underlying mechanism. The adult mice were subjected to endovascular perforation SAH model or sham operation. Mice were randomized to sham group, SAH group, or SAH+NBP group. The EBI (short-term study) was studied at 48 h post-SAH and delayed neurological dysfunction (long-term study) at 21 days post-SAH. The results suggested that NBP evidently alleviated the EBI in mice at 48 h post-SAH, as shown by elevating neurological score, reducing brain edema, blood–brain barrier disruption, neuronal loss, and astrocyte aggregation, as well as ameliorating cerebral vasospasm. Moreover, NBP was able to improve long-term neurobehavioral functions and decrease neuronal apoptosis at 21 days after SAH. Significantly, NBP treatment also inhibited the expressions of NLRP3, ASC, caspase-1, cleaved-caspase-1, IL-1β, IL-18, GSDMD and GSDMD-N in both EBI and delayed neurological dysfunction induced by SAH. Our findings suggested that NBP treatment exerts a profound neuroprotective effect against early brain injury and delayed neurological dysfunction induced by SAH, at least partially through regulating NLRP3 inflammasome signaling pathway and its related inflammation and pyroptosis,
期刊介绍:
The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.