Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice
Abstract Mild traumatic brain injury (mTBI) induced by low-intensity blast (LIB) is a serious health problem affecting military service members and veterans. Our previous reports using a single open-field LIB mouse model showed the absence of gross microscopic damage or necrosis in the brain, while...
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| Format: | Article |
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BMC
2023-09-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01636-4 |
| _version_ | 1797555817029828608 |
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| author | Chao Li Shanyan Chen Heather R. Siedhoff DeAna Grant Pei Liu Ashley Balderrama Marcus Jackson Amitai Zuckerman C. Michael Greenlief Firas Kobeissy Kevin W. Wang Ralph G. DePalma Ibolja Cernak Jiankun Cui Zezong Gu |
| author_facet | Chao Li Shanyan Chen Heather R. Siedhoff DeAna Grant Pei Liu Ashley Balderrama Marcus Jackson Amitai Zuckerman C. Michael Greenlief Firas Kobeissy Kevin W. Wang Ralph G. DePalma Ibolja Cernak Jiankun Cui Zezong Gu |
| author_sort | Chao Li |
| collection | DOAJ |
| description | Abstract Mild traumatic brain injury (mTBI) induced by low-intensity blast (LIB) is a serious health problem affecting military service members and veterans. Our previous reports using a single open-field LIB mouse model showed the absence of gross microscopic damage or necrosis in the brain, while transmission electron microscopy (TEM) identified ultrastructural abnormalities of myelin sheaths, mitochondria, and synapses. The neurovascular unit (NVU), an anatomical and functional system with multiple components, is vital for the regulation of cerebral blood flow and cellular interactions. In this study, we delineated ultrastructural abnormalities affecting the NVU in mice with LIB exposure quantitatively and qualitatively. Luminal constrictive irregularities were identified at 7 days post-injury (DPI) followed by dilation at 30 DPI along with degeneration of pericytes. Quantitative proteomic analysis identified significantly altered vasomotor-related proteins at 24 h post-injury. Endothelial cell, basement membrane and astrocyte end-foot swellings, as well as vacuole formations, occurred in LIB-exposed mice, indicating cellular edema. Structural abnormalities of tight junctions and astrocyte end-foot detachment from basement membranes were also noted. These ultrastructural findings demonstrate that LIB induces multiple-component NVU damage. Prevention of NVU damage may aid in identifying therapeutic targets to mitigate the effects of primary brain blast injury. |
| first_indexed | 2024-03-10T16:53:01Z |
| format | Article |
| id | doaj.art-80b1dd144e7f414d8fa106ec1a5e25e8 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-10T16:53:01Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-80b1dd144e7f414d8fa106ec1a5e25e82023-11-20T11:15:04ZengBMCActa Neuropathologica Communications2051-59602023-09-0111111510.1186/s40478-023-01636-4Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in miceChao Li0Shanyan Chen1Heather R. Siedhoff2DeAna Grant3Pei Liu4Ashley Balderrama5Marcus Jackson6Amitai Zuckerman7C. Michael Greenlief8Firas Kobeissy9Kevin W. Wang10Ralph G. DePalma11Ibolja Cernak12Jiankun Cui13Zezong Gu14Department of Pathology & Anatomical Sciences, University of Missouri School of MedicineDepartment of Pathology & Anatomical Sciences, University of Missouri School of MedicineDepartment of Pathology & Anatomical Sciences, University of Missouri School of MedicineElectron Microscopy Core Facility, University of MissouriCharles W. Gehrke Proteomic Center, University of MissouriDepartment of Pathology & Anatomical Sciences, University of Missouri School of MedicineDepartment of Pathology & Anatomical Sciences, University of Missouri School of MedicineDepartment of Pathology & Anatomical Sciences, University of Missouri School of MedicineCharles W. Gehrke Proteomic Center, University of MissouriDepartment of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Neuroscience Institute, Morehouse School of MedicineDepartment of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Neuroscience Institute, Morehouse School of MedicineOffice of Research and Development, Department of Veterans AffairsDepartment of Biomedical Sciences, Mercer University School of MedicineDepartment of Pathology & Anatomical Sciences, University of Missouri School of MedicineDepartment of Pathology & Anatomical Sciences, University of Missouri School of MedicineAbstract Mild traumatic brain injury (mTBI) induced by low-intensity blast (LIB) is a serious health problem affecting military service members and veterans. Our previous reports using a single open-field LIB mouse model showed the absence of gross microscopic damage or necrosis in the brain, while transmission electron microscopy (TEM) identified ultrastructural abnormalities of myelin sheaths, mitochondria, and synapses. The neurovascular unit (NVU), an anatomical and functional system with multiple components, is vital for the regulation of cerebral blood flow and cellular interactions. In this study, we delineated ultrastructural abnormalities affecting the NVU in mice with LIB exposure quantitatively and qualitatively. Luminal constrictive irregularities were identified at 7 days post-injury (DPI) followed by dilation at 30 DPI along with degeneration of pericytes. Quantitative proteomic analysis identified significantly altered vasomotor-related proteins at 24 h post-injury. Endothelial cell, basement membrane and astrocyte end-foot swellings, as well as vacuole formations, occurred in LIB-exposed mice, indicating cellular edema. Structural abnormalities of tight junctions and astrocyte end-foot detachment from basement membranes were also noted. These ultrastructural findings demonstrate that LIB induces multiple-component NVU damage. Prevention of NVU damage may aid in identifying therapeutic targets to mitigate the effects of primary brain blast injury.https://doi.org/10.1186/s40478-023-01636-4Open-field blastMild traumatic brain injuryNeurovascular unitTransmission electron microscopyUltrastructural abnormalities |
| spellingShingle | Chao Li Shanyan Chen Heather R. Siedhoff DeAna Grant Pei Liu Ashley Balderrama Marcus Jackson Amitai Zuckerman C. Michael Greenlief Firas Kobeissy Kevin W. Wang Ralph G. DePalma Ibolja Cernak Jiankun Cui Zezong Gu Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice Acta Neuropathologica Communications Open-field blast Mild traumatic brain injury Neurovascular unit Transmission electron microscopy Ultrastructural abnormalities |
| title | Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice |
| title_full | Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice |
| title_fullStr | Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice |
| title_full_unstemmed | Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice |
| title_short | Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice |
| title_sort | low intensity open field blast exposure effects on neurovascular unit ultrastructure in mice |
| topic | Open-field blast Mild traumatic brain injury Neurovascular unit Transmission electron microscopy Ultrastructural abnormalities |
| url | https://doi.org/10.1186/s40478-023-01636-4 |
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