Proteomics analysis after traumatic brain injury in rats: the search for potential biomarkers

Ding, Jun; Ding, Zhengang; Yuan, Fang; Guo, Jianyi; Chen, Hao; Gao, Wenwei; Ren, Wei; Gu, Yi; Chen, Jiong; Guo, Yan; Huang, Tian

doi:10.1590/0004-282x20150006

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…Additional forms of analysis could employ a multiple protein target analysis using a multiplex ELISA method or protein array chips (Buttram et al, 2007; Mukherjee et al, 2011; Gyorgy et al, 2010; Kovesdi et al, 2012). For a yet larger scale detection of proteins changed by TBI, one could employ a mass spectrometry analysis approach (Ding et al, 2015; Sheth et al, 2015; Walls et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

Tweedie

Rachmany

Kim

et al. 2016

Journal of Neuroscience Methods

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Background Neurological dysfunction after traumatic brain injury (TBI) poses short-term or long-lasting health issues for family members and health care providers. Presently there are no approved medicines to treat TBI. Epidemiological evidence suggests that TBI may cause neurodegenerative disease later in life. In an effort to illuminate target cellular processes for drug development, we examined the effects of a mild TBI on hippocampal gene expression in mouse. Methods mTBI was induced in a closed head, weight drop-system in mice (ICR). Animals were anesthetized and subjected to mTBI (30 g). Fourteen days after injury the ipsilateral hippocampus was utilized for cDNA gene array studies. mTBI animals were compared with sham-operated animals. Genes regulated by TBI were identified to define TBI-induced physiological/pathological processes. mTBI regulated genes were divided into functional groupings to provide gene ontologies. Genes were further divided to identify molecular/cellular pathways regulated by mTBI. Results Numerous genes were regulated after a single mTBI event that mapped to many ontologies and molecular pathways related to inflammation and neurological physiology/pathology, including neurodegenerative disease. Conclusions These data illustrate diverse transcriptional changes in hippocampal tissues triggered by a single mild injury. The systematic analysis of individual genes that lead to the identification of functional categories, such as gene ontologies and then molecular pathways, illustrate target processes of relevance to TBI pathology. These processes may be further dissected to identify key factors that can be evaluated at the protein level to highlight possible treatments for TBI in human disease and potential biomarkers of neurodegenerative processes.

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Section: Discussionmentioning

confidence: 99%

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

Tweedie

Rachmany

Kim

et al. 2016

Journal of Neuroscience Methods

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“…Further, glutamate excitotoxicity which potentially contributes to neuronal damage was prominent in PC. On the other hand, neuroprotective and cell proliferative events that prevent neuronal damage such as elevated antioxidants enzymes, astrogliosis (Ding et al, 2015; Ekmark‐Lewén et al, 2010; Harish et al, 2015; Trautz et al, 2019), increased myelination were noted in PC. Damage‐associated molecular patterns (DAMPs) proteins (which are released from damaged tissue to stimulate an immune response) (Sharma & Naidu, 2016) and heat shock proteins were significantly higher in PC.…”

Section: Discussionmentioning

confidence: 99%

Neuroanatomical zones of human traumatic brain injury reveal significant differences in protein profile and protein oxidation: Implications for secondary injury events

Gowthami,

Pursotham,

Dey

et al. 2023

Journal of Neurochemistry

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Traumatic brain injury (TBI) causes significant neurological deficits and long‐term degenerative changes. Primary injury in TBI entails distinct neuroanatomical zones, i.e., contusion (Ct) and pericontusion (PC). Their dynamic expansion could contribute to unpredictable neurological deterioration in patients. Molecular characterization of these zones compared with away from contusion (AC) zone is invaluable for TBI management. Using proteomics‐based approach, we were able to distinguish Ct, PC and AC zones in human TBI brains. Ct was associated with structural changes (blood–brain barrier (BBB) disruption, neuroinflammation, axonal injury, demyelination and ferroptosis), while PC was associated with initial events of secondary injury (glutamate excitotoxicity, glial activation, accumulation of cytoskeleton proteins, oxidative stress, endocytosis) and AC displayed mitochondrial dysfunction that could contribute to secondary injury events and trigger long‐term degenerative changes. Phosphoproteome analysis in these zones revealed that certain differentially phosphorylated proteins synergistically contribute to the injury events along with the differentially expressed proteins. Non‐synaptic mitochondria (ns‐mito) was associated with relatively more differentially expressed proteins (DEPs) compared to synaptosomes (Syn), while the latter displayed increased protein oxidation including tryptophan (Trp) oxidation. Proteomic analysis of immunocaptured complex I (CI) from Syn revealed increased Trp oxidation in Ct > PC > AC (vs. control). Oxidized W272 in the ND1 subunit of CI, revealed local conformational changes in ND1 and the neighboring subunits, as indicated by molecular dynamics simulation (MDS). Taken together, neuroanatomical zones in TBI show distinct protein profile and protein oxidation representing different primary and secondary injury events with potential implications for TBI pathology and neurological status of the patients.image

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“…Even though no chronic timepoints were examined in this study, their work nevertheless supports the early involvement of dysfunctional mitochondrial bioenergetics in TBI which is known to precipitate a host of different responses such as oxidative stress, calcium dis-homeostasis, excitotoxicity, and ATP depletion (Opii et al., 2007). Another model that explored effects of fluid percussion (moderate) injury in rat cortical tissue 48 hr after injury using 2D gel electrophoresis and MS/MS analysis also reported significant changes in mitochondrial proteins associated with energy metabolism, cytoskeletal proteins, hormonal signaling receptors, and synaptic proteins (Ding et al., 2015).…”

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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Proteomics analysis after traumatic brain injury in rats: the search for potential biomarkers

Cited by 10 publications

References 29 publications

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

Neuroanatomical zones of human traumatic brain injury reveal significant differences in protein profile and protein oxidation: Implications for secondary injury events

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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