Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice

Acta Neuropathologica Communications

Research

Pei Liu¹  C. Michael Greenlief¹  Ibolja Cernak²  Firas Kobeissy³  Kevin W. Wang³  Marcus Jackson⁴  Chao Li⁵  Ashley Balderrama⁶  Jiankun Cui⁶  Shanyan Chen⁶  Heather R. Siedhoff⁶  Amitai Zuckerman⁶  Zezong Gu⁶  DeAna Grant⁷  Ralph G. DePalma⁸ 

[1] Charles W. Gehrke Proteomic Center, University of Missouri, 65211, Columbia, MO, USA;Department of Biomedical Sciences, Mercer University School of Medicine, 31207, Macon, GA, USA;Department of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Neuroscience Institute, Morehouse School of Medicine, 30310-1458, Atlanta, GA, USA;Atlanta VA Medical and Rehab Center, 30033, Decatur, GA, USA;Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, One Hospital Drive, Medical Science Building, M741, 65212, Columbia, MO, USA;Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, One Hospital Drive, Medical Science Building, M741, 65212, Columbia, MO, USA;Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 510630, Guangzhou, Guangdong, China;Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, One Hospital Drive, Medical Science Building, M741, 65212, Columbia, MO, USA;Truman VA Hospital Research Service, 65201, Columbia, MO, USA;Electron Microscopy Core Facility, University of Missouri, 65211, Columbia, MO, USA;Office of Research and Development, Department of Veterans Affairs, 20420, Washington, DC, USA;Department of Surgery, Uniformed Services University of the Health Sciences, 20814, Bethesda, MD, USA;

关键词: Open-field blast;    Mild traumatic brain injury;    Neurovascular unit;    Transmission electron microscopy;    Ultrastructural abnormalities;   

DOI  :  10.1186/s40478-023-01636-4

 received in 2023-06-03, accepted in 2023-08-14,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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