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Future Science OA Jul 2023Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide resulting from falls, car accidents, sports, and blast injuries. TBI is... (Review)
Review
Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide resulting from falls, car accidents, sports, and blast injuries. TBI is characterized by severe, life-threatening consequences due to neuroinflammation in the brain. Contact and collision sports lead to higher disability and death rates among young adults. Unfortunately, no therapy or drug protocol currently addresses the complex pathophysiology of TBI, leading to the long-term chronic neuroinflammatory assaults. However, the immune response plays a crucial role in tissue-level injury repair. This review aims to provide a better understanding of TBI's immunobiology and management protocols from an immunopathological perspective. It further elaborates on the risk factors, disease outcomes, and preclinical studies to design precisely targeted interventions for enhancing TBI outcomes.
PubMed: 37228857
DOI: 10.2144/fsoa-2023-0037 -
BMJ Military Health Aug 2023'Primary' blast injuries (PBIs) are caused by direct blast wave interaction with the human body, particularly affecting air-containing organs. With continued...
'Primary' blast injuries (PBIs) are caused by direct blast wave interaction with the human body, particularly affecting air-containing organs. With continued experimental focus on PBI mechanisms, recently on blast traumatic brain injury, meaningful test outcomes rely on appropriate simulated conditions. Selected PBI predictive criteria (grouped into those affecting the auditory system, pulmonary injuries and brain trauma) are combined and plotted to provide rationale for generating clinically relevant loading conditions. Using blast engineering theory, explosion characteristics including blast wave parameters and fireball dimensions were calculated for a range of charge masses assuming hemispherical surface detonations and compared with PBI criteria. While many experimental loading conditions are achievable, this analysis demonstrated limits that should be observed to ensure loading is clinically relevant, realistic and practical. For PBI outcomes sensitive only to blast overpressure, blast scaled distance was demonstrated to be a useful parameter for guiding experimental design as it permits flexibility for different experimental set-ups. This analysis revealed that blast waves should correspond to blast scaled distances of 1.75
Blast waves with positive phase durations (2-10 ms) are more practical to achieve through experimental approaches, while representing realistic threats such as improvised explosive devices (ie, 1-50 kg trinitrotoluene equivalent). These guidelines can be used by researchers to inform the design of appropriate blast loading conditions in PBI experimental investigations. Topics: Humans; Explosions; Blast Injuries; Brain Injuries, Traumatic
PubMed: 34035162
DOI: 10.1136/bmjmilitary-2021-001796 -
Scientific Data Sep 2023As a significant type of traumatic brain injury (TBI), blast-induced traumatic brain injury (bTBI) frequently results in severe neurological and psychological...
As a significant type of traumatic brain injury (TBI), blast-induced traumatic brain injury (bTBI) frequently results in severe neurological and psychological impairments. Due to its unique mechanistic and clinical features, bTBI presents diagnostic and therapeutic challenges compared to other TBI forms. The hippocampus, an important site for secondary injury of bTBI, serves as a key niche for neural regeneration and repair post-injury, and is closely associated with the neurological outcomes of bTBI patients. Nonetheless, the pathophysiological alterations of hippocampus underpinning bTBI remain enigmatic, and a corresponding transcriptomic dataset for research reference is yet to be established. In this investigation, the single-nucleus RNA sequencing (snRNA-seq) technique was employed to sequence individual hippocampal nuclei of mice from bTBI and sham group. Upon stringent quality control, gene expression data from 17,278 nuclei were obtained, with the dataset's reliability substantiated through various analytical methods. This dataset holds considerable potential for exploring secondary hippocampal injury and neurogenesis mechanisms following bTBI, with important reference value for the identification of specific diagnostic and therapeutic targets for bTBI.
Topics: Animals; Mice; Brain Injuries, Traumatic; Gene Expression Profiling; Hippocampus; Reproducibility of Results; Transcriptome
PubMed: 37730716
DOI: 10.1038/s41597-023-02552-x -
Acta Neuropathologica Communications Sep 2023Mild traumatic brain injury (mTBI) induced by low-intensity blast (LIB) is a serious health problem affecting military service members and veterans. Our previous reports...
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.
Topics: Animals; Mice; Proteomics; Blast Injuries; Brain Concussion; Arvicolinae; Basement Membrane; Brain Injuries
PubMed: 37674234
DOI: 10.1186/s40478-023-01636-4 -
International Journal of Molecular... Jan 2024Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that... (Review)
Review
Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood-brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury.
Topics: Animals; Humans; Blast Injuries; Endothelial Cells; Brain Concussion; Vascular System Injuries; Astrocytes; Inflammation
PubMed: 38256223
DOI: 10.3390/ijms25021150