γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice
Abstract Background Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. Methods In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cel...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-017-1029-9 |
| _version_ | 1818479349580431360 |
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| author | Xiaoli Zhang Eridan Rocha-Ferreira Tao Li Regina Vontell Darakhshan Jabin Sha Hua Kai Zhou Arshed Nazmi Anna-Maj Albertsson Kristina Sobotka Joakim Ek Claire Thornton Henrik Hagberg Carina Mallard Jianmei W. Leavenworth Changlian Zhu Xiaoyang Wang |
| author_facet | Xiaoli Zhang Eridan Rocha-Ferreira Tao Li Regina Vontell Darakhshan Jabin Sha Hua Kai Zhou Arshed Nazmi Anna-Maj Albertsson Kristina Sobotka Joakim Ek Claire Thornton Henrik Hagberg Carina Mallard Jianmei W. Leavenworth Changlian Zhu Xiaoyang Wang |
| author_sort | Xiaoli Zhang |
| collection | DOAJ |
| description | Abstract Background Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. Methods In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (αβT cells and γδT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) δ-deficient (Tcrd −/−, lacking γδT cells), and TCRα-deficient (Tcra −/−, lacking αβT cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2. Brain myelination was examined at PNDs 12, 26, and 60. Motor function and anxiety-like behavior were evaluated at PND 26 or 30 using DigiGait analysis and an elevated plus maze. Results White matter development was normal in Tcrd −/− and Tcrα −/− compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcrα −/− mice, but not in the Tcrd −/− mice, compared with the saline-treated groups. Neither LPS administration nor the T cell deficiency affected anxiety behavior in these mice as determined with the elevated plus maze. DigiGait analysis revealed motor function deficiency after LPS-induced sepsis in both WT and Tcrα −/− mice, but no such effect was observed in Tcrd −/− mice. Conclusions Our results suggest that γδT cells but not αβT cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of γδT cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury. |
| first_indexed | 2024-12-10T11:09:25Z |
| format | Article |
| id | doaj.art-276da570d75741afae90b0afb0ef2447 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-10T11:09:25Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-276da570d75741afae90b0afb0ef24472022-12-22T01:51:27ZengBMCJournal of Neuroinflammation1742-20942017-12-0114111210.1186/s12974-017-1029-9γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in miceXiaoli Zhang0Eridan Rocha-Ferreira1Tao Li2Regina Vontell3Darakhshan Jabin4Sha Hua5Kai Zhou6Arshed Nazmi7Anna-Maj Albertsson8Kristina Sobotka9Joakim Ek10Claire Thornton11Henrik Hagberg12Carina Mallard13Jianmei W. Leavenworth14Changlian Zhu15Xiaoyang Wang16Henan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Sahlgrenska Academy, University of GothenburgHenan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou UniversityDepartment of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ HospitalPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Obstetrics and Gynecology, Sahlgrenska Academy, University of GothenburgPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ HospitalPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Neurosurgery, The University of Alabama at BirminghamHenan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou UniversityPerinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgAbstract Background Infection and sepsis are associated with brain white matter injury in preterm infants and the subsequent development of cerebral palsy. Methods In the present study, we used a neonatal mouse sepsis-induced white matter injury model to determine the contribution of different T cell subsets (αβT cells and γδT cells) to white matter injury and consequent behavioral changes. C57BL/6J wild-type (WT), T cell receptor (TCR) δ-deficient (Tcrd −/−, lacking γδT cells), and TCRα-deficient (Tcra −/−, lacking αβT cells) mice were administered with lipopolysaccharide (LPS) at postnatal day (PND) 2. Brain myelination was examined at PNDs 12, 26, and 60. Motor function and anxiety-like behavior were evaluated at PND 26 or 30 using DigiGait analysis and an elevated plus maze. Results White matter development was normal in Tcrd −/− and Tcrα −/− compared to WT mice. LPS exposure induced reductions in white matter tissue volume in WT and Tcrα −/− mice, but not in the Tcrd −/− mice, compared with the saline-treated groups. Neither LPS administration nor the T cell deficiency affected anxiety behavior in these mice as determined with the elevated plus maze. DigiGait analysis revealed motor function deficiency after LPS-induced sepsis in both WT and Tcrα −/− mice, but no such effect was observed in Tcrd −/− mice. Conclusions Our results suggest that γδT cells but not αβT cells contribute to sepsis-induced white matter injury and subsequent motor function abnormalities in early life. Modulating the activity of γδT cells in the early stages of preterm white matter injury might represent a novel therapeutic strategy for the treatment of perinatal brain injury.http://link.springer.com/article/10.1186/s12974-017-1029-9SepsisWhite matter injuryT lymphocytesBehavior testsPreterm |
| spellingShingle | Xiaoli Zhang Eridan Rocha-Ferreira Tao Li Regina Vontell Darakhshan Jabin Sha Hua Kai Zhou Arshed Nazmi Anna-Maj Albertsson Kristina Sobotka Joakim Ek Claire Thornton Henrik Hagberg Carina Mallard Jianmei W. Leavenworth Changlian Zhu Xiaoyang Wang γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice Journal of Neuroinflammation Sepsis White matter injury T lymphocytes Behavior tests Preterm |
| title | γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice |
| title_full | γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice |
| title_fullStr | γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice |
| title_full_unstemmed | γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice |
| title_short | γδT cells but not αβT cells contribute to sepsis-induced white matter injury and motor abnormalities in mice |
| title_sort | γδt cells but not αβt cells contribute to sepsis induced white matter injury and motor abnormalities in mice |
| topic | Sepsis White matter injury T lymphocytes Behavior tests Preterm |
| url | http://link.springer.com/article/10.1186/s12974-017-1029-9 |
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