Proteomic Analysis and Biochemical Correlates of Mitochondrial Dysfunction after Low-Intensity Primary Blast Exposure

Song, Hailong; Chen, Mei; Chen, Chen; Cui, Jiankun; Johnson, Catherine E.; Cheng, Jianlin; Wang, Xiaowan; Swerdlow, Russell H.; DePalma, Ralph G.; Xia, Weiming; Z, Gu

doi:10.1089/neu.2018.6114

Cited by 31 publications

(31 citation statements)

References 57 publications

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“…In general, animal studies of LLB articulated methods to induce blast exposure in well-controlled environments ( 45 – 66 ), examined longitudinal outcomes associated with LLB ( 46 , 64 ) or repeated exposures to LLB ( 49 ), or assessed the impact of environmental characteristics on outcomes associated with LLB ( 58 ). Studies frequently examined neurological outcomes, such as neuroinflammation and neurodegeneration ( 51 , 57 , 61 – 63 ) and damage to specific brain regions or types of cells ( 53 , 65 ). Animal studies also examined outcomes related to mental health ( 54 , 55 ) and auditory ( 47 ), visual ( 48 , 56 ), vestibular ( 52 ), and vascular ( 50 ) systems.…”

Section: Resultsmentioning

confidence: 99%

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Potential Health and Performance Effects of High-Level and Low-Level Blast: A Scoping Review of Two Decades of Research

et al. 2021

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Although blast exposure has been recognized as a significant source of morbidity and mortality in military populations, our understanding of the effects of blast exposure, particularly low-level blast (LLB) exposure, on health outcomes remains limited. This scoping review provides a comprehensive, accessible review of the peer-reviewed literature that has been published on blast exposure over the past two decades, with specific emphasis on LLB. We conducted a comprehensive scoping review of the scientific literature published between January 2000 and 2019 pertaining to the effects of blast injury and/or exposure on human and animal health. A three-level review process with specific inclusion and exclusion criteria was used. A full-text review of all articles pertaining to LLB exposure was conducted and relevant study characteristics were extracted. The research team identified 3,215 blast-relevant articles, approximately half of which (55.4%) studied live humans, 16% studied animals, and the remainder were non-subjects research (e.g., literature reviews). Nearly all (99.49%) of the included studies were conducted by experts in medicine or epidemiology; approximately half of these articles were categorized into more than one medical specialty. Among the 51 articles identified as pertaining to LLB specifically, 45.1% were conducted on animals and 39.2% focused on human subjects. Animal studies of LLB predominately used shock tubes to induce various blast exposures in rats, assessed a variety of outcomes, and clearly demonstrated that LLB exposure is associated with brain injury. In contrast, the majority of LLB studies on humans were conducted among military and law enforcement personnel in training environments and had remarkable variability in the exposures and outcomes assessed. While findings suggest that there is the potential for LLB to harm human populations, findings are mixed and more research is needed. Although it is clear that more research is needed on this rapidly growing topic, this review highlights the detrimental effects of LLB on the health of both animals and humans. Future research would benefit from multidisciplinary collaboration, larger sample sizes, and standardization of terminology, exposures, and outcomes.

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Section: Resultsmentioning

confidence: 99%

“…Sample sizes in studies using rats ranged from 10 to 180, with 75% of studies including fewer than 100 subjects. Other species studied included mice ( 46 , 52 , 63 , 64 ), pigs ( 58 ), and chinchillas ( 47 ). Sample size for these species varied from 14 (chinchillas) to 115 (pigs).…”

Section: Resultsmentioning

confidence: 99%

Potential Health and Performance Effects of High-Level and Low-Level Blast: A Scoping Review of Two Decades of Research

et al. 2021

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“…In the context of low level exposure without a direct impact to the head, this study indicated that median levels of serum Nf-L and tau were elevated (although tau did not meet statistical thresholds). Exposure is reported to impact brain tissues in a way that may mirror a sub-concussive event [24,25], causing cytoskeletal abnormalities and demyelination in rodent models [26][27][28]. In animal models, serum tau is elevated within 6h-1d of and the heavy chain isoform of neurofilament is increased within 2h after mild exposure [29].…”

Section: A Subset Of Tbi-related Proteins Are Potential Biomarkers Ofmentioning

confidence: 99%

Brain-related proteins as serum biomarkers of acute, subconcussive blast overpressure exposure: A cohort study of military personnel

et al. 2019

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Repeated exposure to blast overpressure remains a major cause of adverse health for military personnel who, as a consequence, are at a higher risk for neurodegenerative disease and suicide. Acute, early tracking of blast related effects holds the promise of rapid health assessment prior to onset of chronic problems. Current techniques used to determine blastrelated effects rely upon reporting of symptomology similar to that of concussion and neurocognitive assessment relevant to operational decrement. Here, we describe the results of a cross sectional study with pared observations. The concentration of multiple TBI-related proteins was tested in serum collected within one hour of blast exposure as a quantitative and minimally invasive strategy to augment assessment of blast-exposure effects that are associated with concussion-like symptomology and reaction time decrements. We determined that median simple reaction time (SRT) was slowed in accordance with serum Nf-L, tau, Aβ-40, and Aβ-42 elevation after overpressure exposure. In contrast, median levels of serum GFAP decreased. Individual, inter-subject analysis revealed positive correlations between changes in Nf-L and GFAP, and in Aβ-40 compared to Aβ-42. The change in Nf-L was negatively associated with tau, Aβ-40, and Aβ-42. Participants reported experiencing headaches, dizziness and taking longer to think. Dizziness was associated with reaction time decrements, GFAP or NfL suppression, as well as Aβ peptide elevation. UCH-L1 elevation had a weak association with mTBI/concussion history. Multiplexed serum biomarker quantitation, coupled with reaction time assessment and symptomology determined before and after blast exposure, may serve as a platform for tracking adverse effects in the absence of a head wound or diagnosed concussion. We propose further evaluation of serum biomarkers, which are often associated with TBI, in the context of acute operational blast exposures.

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“…Quantitative TMT proteomic studies have also been conducted in single low-intensity blast (mTBI) injury studies at 2 and 24 hr, and 7 and 30 days postinjury (Song et al., 2019). Animals revealed mitochondrial and axonal ultrastructural changes.…”

Section: Discussionmentioning

confidence: 99%

Unbiased Proteomic Approach Identifies Pathobiological Profiles in the Brains of Preclinical Models of Repetitive Mild Traumatic Brain Injury, Tauopathy, and Amyloidosis

et al. 2020

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No concerted investigation has been conducted to explore overlapping and distinct pathobiological mechanisms between repetitive mild traumatic brain injury (r-mTBI) and tau/amyloid proteinopathies considering the long history of association between TBI and Alzheimer's disease. We address this problem by using unbiased proteomic approaches to generate detailed time-dependent brain molecular profiles of response to repetitive mTBI in C57BL/6 mice and in mouse models of amyloidosis (with amyloid precursor protein KM670/671NL (Swedish) and Presenilin 1 M146L mutations [PSAPP]) and tauopathy (hTau). Brain tissues from animals were collected at different timepoints after injuries (24 hr-12 months postinjury) and at different ages for tau or amyloid transgenic models (3, 9, and 15 months old), encompassing the pre-, peri-, and post-"onset" of cognitive and pathological phenotypes. We identified 30 hippocampal and 47 cortical proteins that were significantly modulated over time in the r-mTBI compared with sham mice. These proteins identified TBI-dependent modulation of phosphatidylinositol-3-kinase/AKT signaling, protein kinase A signaling, and PPARa/RXRa activation in the hippocampus and protein kinase A signaling, gonadotropin-releasing hormone signaling, and B cell receptor signaling in the cortex. Previously published neuropathological studies of our mTBI model showed a lack of amyloid and tau pathology. In PSAPP mice, we identified 19 proteins significantly changing in the cortex and only 7 proteins in hTau mice versus wild-type littermates. When we explored the overlap between our r-mTBI model and the PSAPP/hTau models, a fairly small coincidental change was observed involving only eight significantly regulated proteins. This work suggests a very distinct TBI neurodegeneration and also that other factors are needed to drive pathologies such as amyloidosis and tauopathy postinjury.

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Proteomic Analysis and Biochemical Correlates of Mitochondrial Dysfunction after Low-Intensity Primary Blast Exposure

Cited by 31 publications

References 57 publications

Potential Health and Performance Effects of High-Level and Low-Level Blast: A Scoping Review of Two Decades of Research

Potential Health and Performance Effects of High-Level and Low-Level Blast: A Scoping Review of Two Decades of Research

Brain-related proteins as serum biomarkers of acute, subconcussive blast overpressure exposure: A cohort study of military personnel

Unbiased Proteomic Approach Identifies Pathobiological Profiles in the Brains of Preclinical Models of Repetitive Mild Traumatic Brain Injury, Tauopathy, and Amyloidosis

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