Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability
Abstract Traumatic brain injury is a leading cause of chronic neurologic disability and a risk factor for development of neurodegenerative disease. However, little is known regarding the pathophysiology of human traumatic brain injury, especially in the window after acute injury and the later life d...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-024-03328-9 |
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| author | Alicia B. Feichtenbiner Karinn Sytsma Ryan P. O’Boyle Rhonda Mittenzwei Heather Maioli Kathryn P. Scherpelz Daniel D. Child Ning Li Jeanelle Ariza Torres Lisa Keene Amanda Kirkland Kimberly Howard Caitlin Latimer C. Dirk Keene Christopher Ransom Amber L. Nolan |
| author_facet | Alicia B. Feichtenbiner Karinn Sytsma Ryan P. O’Boyle Rhonda Mittenzwei Heather Maioli Kathryn P. Scherpelz Daniel D. Child Ning Li Jeanelle Ariza Torres Lisa Keene Amanda Kirkland Kimberly Howard Caitlin Latimer C. Dirk Keene Christopher Ransom Amber L. Nolan |
| author_sort | Alicia B. Feichtenbiner |
| collection | DOAJ |
| description | Abstract Traumatic brain injury is a leading cause of chronic neurologic disability and a risk factor for development of neurodegenerative disease. However, little is known regarding the pathophysiology of human traumatic brain injury, especially in the window after acute injury and the later life development of progressive neurodegenerative disease. Given the proposed mechanisms of toxic protein production and neuroinflammation as possible initiators or contributors to progressive pathology, we examined phosphorylated tau accumulation, microgliosis and astrogliosis using immunostaining in the orbitofrontal cortex, a region often vulnerable across traumatic brain injury exposures, in an age and sex-matched cohort of community traumatic brain injury including both mild and severe cases in midlife. We found that microglial response is most prominent after chronic traumatic brain injury, and interactions with neurons in the form of satellite microglia are increased, even after mild traumatic brain injury. Taking our investigation into a mouse model, we identified that these satellite microglia suppress neuronal excitability in control conditions but lose this ability with chronic traumatic brain injury. At the same time, network hyperexcitability is present in both mouse and human orbitofrontal cortex. Our findings support a role for loss of homeostatic control by satellite microglia in the maladaptive circuit changes that occur after traumatic brain injury. |
| format | Article |
| id | doaj-art-80386a70b22f4e6fa14036c8297930f9 |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-80386a70b22f4e6fa14036c8297930f92025-01-19T12:33:25ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111710.1186/s12974-024-03328-9Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitabilityAlicia B. Feichtenbiner0Karinn Sytsma1Ryan P. O’Boyle2Rhonda Mittenzwei3Heather Maioli4Kathryn P. Scherpelz5Daniel D. Child6Ning Li7Jeanelle Ariza Torres8Lisa Keene9Amanda Kirkland10Kimberly Howard11Caitlin Latimer12C. Dirk Keene13Christopher Ransom14Amber L. Nolan15Department of Laboratory Medicine and Pathology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonMiller School of Medicine, University of MiamiDepartment of Laboratory Medicine and Pathology, University of WashingtonOffice of Chief Medical Examiner of the City of New YorkDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Neurology, University of WashingtonAllen InstituteDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Neurology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonAbstract Traumatic brain injury is a leading cause of chronic neurologic disability and a risk factor for development of neurodegenerative disease. However, little is known regarding the pathophysiology of human traumatic brain injury, especially in the window after acute injury and the later life development of progressive neurodegenerative disease. Given the proposed mechanisms of toxic protein production and neuroinflammation as possible initiators or contributors to progressive pathology, we examined phosphorylated tau accumulation, microgliosis and astrogliosis using immunostaining in the orbitofrontal cortex, a region often vulnerable across traumatic brain injury exposures, in an age and sex-matched cohort of community traumatic brain injury including both mild and severe cases in midlife. We found that microglial response is most prominent after chronic traumatic brain injury, and interactions with neurons in the form of satellite microglia are increased, even after mild traumatic brain injury. Taking our investigation into a mouse model, we identified that these satellite microglia suppress neuronal excitability in control conditions but lose this ability with chronic traumatic brain injury. At the same time, network hyperexcitability is present in both mouse and human orbitofrontal cortex. Our findings support a role for loss of homeostatic control by satellite microglia in the maladaptive circuit changes that occur after traumatic brain injury.https://doi.org/10.1186/s12974-024-03328-9NeuropathologyTraumatic brain injuryMicrogliaCortical circuitsElectrophysiology |
| spellingShingle | Alicia B. Feichtenbiner Karinn Sytsma Ryan P. O’Boyle Rhonda Mittenzwei Heather Maioli Kathryn P. Scherpelz Daniel D. Child Ning Li Jeanelle Ariza Torres Lisa Keene Amanda Kirkland Kimberly Howard Caitlin Latimer C. Dirk Keene Christopher Ransom Amber L. Nolan Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability Journal of Neuroinflammation Neuropathology Traumatic brain injury Microglia Cortical circuits Electrophysiology |
| title | Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability |
| title_full | Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability |
| title_fullStr | Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability |
| title_full_unstemmed | Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability |
| title_short | Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability |
| title_sort | satellite microglia marker of traumatic brain injury and regulator of neuronal excitability |
| topic | Neuropathology Traumatic brain injury Microglia Cortical circuits Electrophysiology |
| url | https://doi.org/10.1186/s12974-024-03328-9 |
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