Theresa C Sutherland, Sighild Lemarchant, Ashley J Douthitt, Alexandra H Lopez, Lily Kuhlman, Darijana Horvat, Arthur Sefiani, Sydney M Johnson, Zoha Hassan, Natalie Bachir, Ravali Dundumulla, Michelle Hook, Yann Godfrin, Cédric G Geoffroy
{"title":"sco - spondnin衍生肽NX210促进小鼠脊髓损伤后功能恢复。","authors":"Theresa C Sutherland, Sighild Lemarchant, Ashley J Douthitt, Alexandra H Lopez, Lily Kuhlman, Darijana Horvat, Arthur Sefiani, Sydney M Johnson, Zoha Hassan, Natalie Bachir, Ravali Dundumulla, Michelle Hook, Yann Godfrin, Cédric G Geoffroy","doi":"10.1177/08977151251359983","DOIUrl":null,"url":null,"abstract":"<p><p>Spinal cord injury (SCI) represents a major public health issue, as the consequences are often irreversible with no treatment currently available. This results in a growing population living with long-lasting motor, sensory, and/or autonomic impairments directly related to their SCI. Here, we have evaluated the therapeutic potential of a thrombospondin repeats peptide analogue, named NX210, in a mouse hemisection model of SCI. Adult female mice were subjected to a thoracic level 8 dorsal hemisection, and treated with intraperitoneal injections of NX210 starting at 4 h post-injury and then twice a week at 4, 8, or 16 mg/kg. Hind limb motor function was assessed once a week for 10 weeks post-injury using the Basso Mouse Scale (BMS) score and sub-score, the rotarod, and the activity chamber tests. Mice were then sacrificed, and the spinal cords were collected for immunohistochemistry. Interestingly, NX210 improved functional recovery (BMS score and sub-score, latency to fall from the rotarod, spontaneous locomotor activity) with rapid rises in function that were maintained throughout the 10-week study. This was accompanied by a reduction of nociceptive reactivity assessed by the tail flick test. NX210 treatment also increased myelin basic protein and reduced neuron/glial antigen 2 at the injury site 10 weeks post-injury while no significant effects were observed on lesion size, inflammation, and neuron survival. Overall, this study highlights a potential new therapeutic strategy to promote repair and decrease long-lasting functional impairments after SCI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SCO-Spondin-Derived Peptide NX210 Promotes Functional Recovery after Spinal Cord Injury in Mice.\",\"authors\":\"Theresa C Sutherland, Sighild Lemarchant, Ashley J Douthitt, Alexandra H Lopez, Lily Kuhlman, Darijana Horvat, Arthur Sefiani, Sydney M Johnson, Zoha Hassan, Natalie Bachir, Ravali Dundumulla, Michelle Hook, Yann Godfrin, Cédric G Geoffroy\",\"doi\":\"10.1177/08977151251359983\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Spinal cord injury (SCI) represents a major public health issue, as the consequences are often irreversible with no treatment currently available. This results in a growing population living with long-lasting motor, sensory, and/or autonomic impairments directly related to their SCI. Here, we have evaluated the therapeutic potential of a thrombospondin repeats peptide analogue, named NX210, in a mouse hemisection model of SCI. Adult female mice were subjected to a thoracic level 8 dorsal hemisection, and treated with intraperitoneal injections of NX210 starting at 4 h post-injury and then twice a week at 4, 8, or 16 mg/kg. Hind limb motor function was assessed once a week for 10 weeks post-injury using the Basso Mouse Scale (BMS) score and sub-score, the rotarod, and the activity chamber tests. Mice were then sacrificed, and the spinal cords were collected for immunohistochemistry. Interestingly, NX210 improved functional recovery (BMS score and sub-score, latency to fall from the rotarod, spontaneous locomotor activity) with rapid rises in function that were maintained throughout the 10-week study. This was accompanied by a reduction of nociceptive reactivity assessed by the tail flick test. NX210 treatment also increased myelin basic protein and reduced neuron/glial antigen 2 at the injury site 10 weeks post-injury while no significant effects were observed on lesion size, inflammation, and neuron survival. Overall, this study highlights a potential new therapeutic strategy to promote repair and decrease long-lasting functional impairments after SCI.</p>\",\"PeriodicalId\":16512,\"journal\":{\"name\":\"Journal of neurotrauma\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of neurotrauma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/08977151251359983\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neurotrauma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/08977151251359983","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
SCO-Spondin-Derived Peptide NX210 Promotes Functional Recovery after Spinal Cord Injury in Mice.
Spinal cord injury (SCI) represents a major public health issue, as the consequences are often irreversible with no treatment currently available. This results in a growing population living with long-lasting motor, sensory, and/or autonomic impairments directly related to their SCI. Here, we have evaluated the therapeutic potential of a thrombospondin repeats peptide analogue, named NX210, in a mouse hemisection model of SCI. Adult female mice were subjected to a thoracic level 8 dorsal hemisection, and treated with intraperitoneal injections of NX210 starting at 4 h post-injury and then twice a week at 4, 8, or 16 mg/kg. Hind limb motor function was assessed once a week for 10 weeks post-injury using the Basso Mouse Scale (BMS) score and sub-score, the rotarod, and the activity chamber tests. Mice were then sacrificed, and the spinal cords were collected for immunohistochemistry. Interestingly, NX210 improved functional recovery (BMS score and sub-score, latency to fall from the rotarod, spontaneous locomotor activity) with rapid rises in function that were maintained throughout the 10-week study. This was accompanied by a reduction of nociceptive reactivity assessed by the tail flick test. NX210 treatment also increased myelin basic protein and reduced neuron/glial antigen 2 at the injury site 10 weeks post-injury while no significant effects were observed on lesion size, inflammation, and neuron survival. Overall, this study highlights a potential new therapeutic strategy to promote repair and decrease long-lasting functional impairments after SCI.
期刊介绍:
Journal of Neurotrauma is the flagship, peer-reviewed publication for reporting on the latest advances in both the clinical and laboratory investigation of traumatic brain and spinal cord injury. The Journal focuses on the basic pathobiology of injury to the central nervous system, while considering preclinical and clinical trials targeted at improving both the early management and long-term care and recovery of traumatically injured patients. This is the essential journal publishing cutting-edge basic and translational research in traumatically injured human and animal studies, with emphasis on neurodegenerative disease research linked to CNS trauma.