Susanne M. Brunner , Stefanie Gaisbauer , Patrick N. Pallier , Ping K. Yip , Andrea Ramspacher , Julia Leitner , Felix Sternberg , Christina Erhardt-Kreutzer , Theresa Haslauer , Sara Huber , Lara Bieler , Sebastien Couillard-Despres , Barbara Kofler
{"title":"甘丙肽受体2和3双敲除对创伤性脑损伤后神经炎症和功能恢复的影响。","authors":"Susanne M. Brunner , Stefanie Gaisbauer , Patrick N. Pallier , Ping K. Yip , Andrea Ramspacher , Julia Leitner , Felix Sternberg , Christina Erhardt-Kreutzer , Theresa Haslauer , Sara Huber , Lara Bieler , Sebastien Couillard-Despres , Barbara Kofler","doi":"10.1016/j.peptides.2025.171415","DOIUrl":null,"url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is one of the world’s leading causes of death and disability in young individuals and the mechanism underlying TBI-associated neuroinflammation is poorly understood. The regulatory neuropeptide galanin (GAL) and its three receptors (GAL<sub>1–3</sub>R) are assumed to modulate the neuroinflammatory response following TBI, especially by signalling via GAL<sub>2</sub>R and GAL<sub>3</sub>R. Therefore, the role of GALRs in acute neuroinflammation and functional recovery following moderate Controlled Cortical Impact TBI was studied using GAL<sub>2/3</sub>R-double-KO (GAL<sub>2/3</sub>R-KO) mice. Brains and cerebrospinal fluid (CSF) were collected at day 1 and 30 days post TBI. Functional recovery post TBI was assessed by the modified Neurological Severity Score (mNSS), Elevated Plus Maze (EPM) and Morris Water Maze (MWM) test. Post TBI (day 1–28 post injury), neurological dysfunction was more severe in GAL<sub>2/3</sub>R-KO mice than in WT mice. At 1 day post TBI, inflammatory markers and several nerve growth factors significantly increased in the ipsilateral hemisphere, compared to the contralateral hemisphere in both GAL<sub>2/3</sub>R-KO and WT mice. At 4 days post surgery, TBI mice entered significantly more frequent the open-arms in the EPM compared to Sham-operated mice, suggestive of increased exploratory behaviour in TBI mice. At 30 days post TBI, immunostaining of brain sections revealed significant differences in vascularisation and glial scarring in the cortex when comparing TBI and Sham-operated mice, but genotypes were similar. In summary, the results indicate that GAL<sub>2</sub>R and/or GAL<sub>3</sub>R have a neuroprotective role following moderate TBI, as the severity was significantly lower in their presence than in their absence.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171415"},"PeriodicalIF":2.9000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of galanin receptors 2 and 3 double-knockout on neuroinflammation and functional recovery following traumatic brain injury\",\"authors\":\"Susanne M. Brunner , Stefanie Gaisbauer , Patrick N. Pallier , Ping K. Yip , Andrea Ramspacher , Julia Leitner , Felix Sternberg , Christina Erhardt-Kreutzer , Theresa Haslauer , Sara Huber , Lara Bieler , Sebastien Couillard-Despres , Barbara Kofler\",\"doi\":\"10.1016/j.peptides.2025.171415\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Traumatic brain injury (TBI) is one of the world’s leading causes of death and disability in young individuals and the mechanism underlying TBI-associated neuroinflammation is poorly understood. The regulatory neuropeptide galanin (GAL) and its three receptors (GAL<sub>1–3</sub>R) are assumed to modulate the neuroinflammatory response following TBI, especially by signalling via GAL<sub>2</sub>R and GAL<sub>3</sub>R. Therefore, the role of GALRs in acute neuroinflammation and functional recovery following moderate Controlled Cortical Impact TBI was studied using GAL<sub>2/3</sub>R-double-KO (GAL<sub>2/3</sub>R-KO) mice. Brains and cerebrospinal fluid (CSF) were collected at day 1 and 30 days post TBI. Functional recovery post TBI was assessed by the modified Neurological Severity Score (mNSS), Elevated Plus Maze (EPM) and Morris Water Maze (MWM) test. Post TBI (day 1–28 post injury), neurological dysfunction was more severe in GAL<sub>2/3</sub>R-KO mice than in WT mice. At 1 day post TBI, inflammatory markers and several nerve growth factors significantly increased in the ipsilateral hemisphere, compared to the contralateral hemisphere in both GAL<sub>2/3</sub>R-KO and WT mice. At 4 days post surgery, TBI mice entered significantly more frequent the open-arms in the EPM compared to Sham-operated mice, suggestive of increased exploratory behaviour in TBI mice. At 30 days post TBI, immunostaining of brain sections revealed significant differences in vascularisation and glial scarring in the cortex when comparing TBI and Sham-operated mice, but genotypes were similar. In summary, the results indicate that GAL<sub>2</sub>R and/or GAL<sub>3</sub>R have a neuroprotective role following moderate TBI, as the severity was significantly lower in their presence than in their absence.</div></div>\",\"PeriodicalId\":19765,\"journal\":{\"name\":\"Peptides\",\"volume\":\"191 \",\"pages\":\"Article 171415\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Peptides\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0196978125000762\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Peptides","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0196978125000762","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Impact of galanin receptors 2 and 3 double-knockout on neuroinflammation and functional recovery following traumatic brain injury
Traumatic brain injury (TBI) is one of the world’s leading causes of death and disability in young individuals and the mechanism underlying TBI-associated neuroinflammation is poorly understood. The regulatory neuropeptide galanin (GAL) and its three receptors (GAL1–3R) are assumed to modulate the neuroinflammatory response following TBI, especially by signalling via GAL2R and GAL3R. Therefore, the role of GALRs in acute neuroinflammation and functional recovery following moderate Controlled Cortical Impact TBI was studied using GAL2/3R-double-KO (GAL2/3R-KO) mice. Brains and cerebrospinal fluid (CSF) were collected at day 1 and 30 days post TBI. Functional recovery post TBI was assessed by the modified Neurological Severity Score (mNSS), Elevated Plus Maze (EPM) and Morris Water Maze (MWM) test. Post TBI (day 1–28 post injury), neurological dysfunction was more severe in GAL2/3R-KO mice than in WT mice. At 1 day post TBI, inflammatory markers and several nerve growth factors significantly increased in the ipsilateral hemisphere, compared to the contralateral hemisphere in both GAL2/3R-KO and WT mice. At 4 days post surgery, TBI mice entered significantly more frequent the open-arms in the EPM compared to Sham-operated mice, suggestive of increased exploratory behaviour in TBI mice. At 30 days post TBI, immunostaining of brain sections revealed significant differences in vascularisation and glial scarring in the cortex when comparing TBI and Sham-operated mice, but genotypes were similar. In summary, the results indicate that GAL2R and/or GAL3R have a neuroprotective role following moderate TBI, as the severity was significantly lower in their presence than in their absence.
期刊介绍:
Peptides is an international journal presenting original contributions on the biochemistry, physiology and pharmacology of biological active peptides, as well as their functions that relate to gastroenterology, endocrinology, and behavioral effects.
Peptides emphasizes all aspects of high profile peptide research in mammals and non-mammalian vertebrates. Special consideration can be given to plants and invertebrates. Submission of articles with clinical relevance is particularly encouraged.