{"title":"骨膜蛋白参与小鼠蛛网膜下腔出血所致急性神经元凋亡及克拉霉素的抑制作用。","authors":"Hiroki Oinaka, Hideki Kanamaru, Fumihiro Kawakita, Yume Suzuki, Hideki Nakajima, Mai Nampei, Hidenori Suzuki","doi":"10.1007/s12028-025-02348-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Periostin is an inflammation-related matricellular protein that has been reported to increase in the acute phase after subarachnoid hemorrhage (SAH) in clinical settings. However, its relationship with neuronal apoptosis, a characteristic of early brain injury, remains unknown. The purpose of this study was to investigate the involvement of periostin in SAH-induced acute neuronal apoptosis and to determine whether clarithromycin (CAM), a macrolide antibiotic known to suppress periostin expression, prevents acute neuronal apoptosis after SAH in mice.</p><p><strong>Methods: </strong>In 141 male C57BL/6 mice undergoing endovascular perforation SAH or sham operation, vehicle or CAM (50 mg/kg) was administered subcutaneously 5 min after surgery, followed by intracerebroventricular administration of vehicle or recombinant mouse periostin (R-periostin) 30 min after surgery. The intervention effects were assessed 24 h after surgery by neurological score, Western blotting, and double immunostaining.</p><p><strong>Results: </strong>After induction of SAH, neurological scores worsened, and caspase-3-dependent neuronal apoptosis was increased, which was associated with upregulation of periostin expression in the left (perforation side) cerebral hemisphere compared with sham-operated animals (p < 0.01 vs. sham + vehicle group, respectively). Administration of CAM improved neurological scores and reduced caspase-3-dependent neuronal apoptosis as well as periostin expression in SAH mice (p < 0.05, p < 0.01, p < 0.01 vs. SAH + vehicle group, respectively). The protective effects of CAM on neurological scores and neuronal apoptosis after SAH were counteracted by administration of R-periostin (SAH + CAM + vehicle group vs. SAH + CAM + R-periostin group, p < 0.05 and p < 0.001, respectively). Immunohistochemical analysis confirmed overexpression of periostin in neurons after SAH, which was attenuated by CAM treatment but re-increased by administration of R-periostin.</p><p><strong>Conclusions: </strong>These findings indicate that periostin-driven signaling contributes to caspase-dependent neuronal apoptosis during early brain injury after SAH. This study highlights periostin as a potential therapeutic target to attenuate SAH-induced acute neuronal apoptosis and demonstrates that CAM holds promise as an antiapoptotic agent through periostin inhibition.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Involvement of Periostin in Acute Neuronal Apoptosis Induced by Subarachnoid Hemorrhage in Mice and its Suppression by Clarithromycin.\",\"authors\":\"Hiroki Oinaka, Hideki Kanamaru, Fumihiro Kawakita, Yume Suzuki, Hideki Nakajima, Mai Nampei, Hidenori Suzuki\",\"doi\":\"10.1007/s12028-025-02348-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Periostin is an inflammation-related matricellular protein that has been reported to increase in the acute phase after subarachnoid hemorrhage (SAH) in clinical settings. However, its relationship with neuronal apoptosis, a characteristic of early brain injury, remains unknown. The purpose of this study was to investigate the involvement of periostin in SAH-induced acute neuronal apoptosis and to determine whether clarithromycin (CAM), a macrolide antibiotic known to suppress periostin expression, prevents acute neuronal apoptosis after SAH in mice.</p><p><strong>Methods: </strong>In 141 male C57BL/6 mice undergoing endovascular perforation SAH or sham operation, vehicle or CAM (50 mg/kg) was administered subcutaneously 5 min after surgery, followed by intracerebroventricular administration of vehicle or recombinant mouse periostin (R-periostin) 30 min after surgery. The intervention effects were assessed 24 h after surgery by neurological score, Western blotting, and double immunostaining.</p><p><strong>Results: </strong>After induction of SAH, neurological scores worsened, and caspase-3-dependent neuronal apoptosis was increased, which was associated with upregulation of periostin expression in the left (perforation side) cerebral hemisphere compared with sham-operated animals (p < 0.01 vs. sham + vehicle group, respectively). Administration of CAM improved neurological scores and reduced caspase-3-dependent neuronal apoptosis as well as periostin expression in SAH mice (p < 0.05, p < 0.01, p < 0.01 vs. SAH + vehicle group, respectively). The protective effects of CAM on neurological scores and neuronal apoptosis after SAH were counteracted by administration of R-periostin (SAH + CAM + vehicle group vs. SAH + CAM + R-periostin group, p < 0.05 and p < 0.001, respectively). Immunohistochemical analysis confirmed overexpression of periostin in neurons after SAH, which was attenuated by CAM treatment but re-increased by administration of R-periostin.</p><p><strong>Conclusions: </strong>These findings indicate that periostin-driven signaling contributes to caspase-dependent neuronal apoptosis during early brain injury after SAH. This study highlights periostin as a potential therapeutic target to attenuate SAH-induced acute neuronal apoptosis and demonstrates that CAM holds promise as an antiapoptotic agent through periostin inhibition.</p>\",\"PeriodicalId\":19118,\"journal\":{\"name\":\"Neurocritical Care\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurocritical Care\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12028-025-02348-4\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurocritical Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12028-025-02348-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Involvement of Periostin in Acute Neuronal Apoptosis Induced by Subarachnoid Hemorrhage in Mice and its Suppression by Clarithromycin.
Background: Periostin is an inflammation-related matricellular protein that has been reported to increase in the acute phase after subarachnoid hemorrhage (SAH) in clinical settings. However, its relationship with neuronal apoptosis, a characteristic of early brain injury, remains unknown. The purpose of this study was to investigate the involvement of periostin in SAH-induced acute neuronal apoptosis and to determine whether clarithromycin (CAM), a macrolide antibiotic known to suppress periostin expression, prevents acute neuronal apoptosis after SAH in mice.
Methods: In 141 male C57BL/6 mice undergoing endovascular perforation SAH or sham operation, vehicle or CAM (50 mg/kg) was administered subcutaneously 5 min after surgery, followed by intracerebroventricular administration of vehicle or recombinant mouse periostin (R-periostin) 30 min after surgery. The intervention effects were assessed 24 h after surgery by neurological score, Western blotting, and double immunostaining.
Results: After induction of SAH, neurological scores worsened, and caspase-3-dependent neuronal apoptosis was increased, which was associated with upregulation of periostin expression in the left (perforation side) cerebral hemisphere compared with sham-operated animals (p < 0.01 vs. sham + vehicle group, respectively). Administration of CAM improved neurological scores and reduced caspase-3-dependent neuronal apoptosis as well as periostin expression in SAH mice (p < 0.05, p < 0.01, p < 0.01 vs. SAH + vehicle group, respectively). The protective effects of CAM on neurological scores and neuronal apoptosis after SAH were counteracted by administration of R-periostin (SAH + CAM + vehicle group vs. SAH + CAM + R-periostin group, p < 0.05 and p < 0.001, respectively). Immunohistochemical analysis confirmed overexpression of periostin in neurons after SAH, which was attenuated by CAM treatment but re-increased by administration of R-periostin.
Conclusions: These findings indicate that periostin-driven signaling contributes to caspase-dependent neuronal apoptosis during early brain injury after SAH. This study highlights periostin as a potential therapeutic target to attenuate SAH-induced acute neuronal apoptosis and demonstrates that CAM holds promise as an antiapoptotic agent through periostin inhibition.
期刊介绍:
Neurocritical Care is a peer reviewed scientific publication whose major goal is to disseminate new knowledge on all aspects of acute neurological care. It is directed towards neurosurgeons, neuro-intensivists, neurologists, anesthesiologists, emergency physicians, and critical care nurses treating patients with urgent neurologic disorders. These are conditions that may potentially evolve rapidly and could need immediate medical or surgical intervention. Neurocritical Care provides a comprehensive overview of current developments in intensive care neurology, neurosurgery and neuroanesthesia and includes information about new therapeutic avenues and technological innovations. Neurocritical Care is the official journal of the Neurocritical Care Society.