Novel neuroproteomic approaches to studying traumatic brain injury

Ottens, Andrew K.; Kobeissy, Firas; Fuller, Brian F.; Liu, Ming Chen; Oli, Monika W.; Hayes, Ronald L.; Wang, Kevin

doi:10.1016/s0079-6123(06)61029-7

Cited by 45 publications

(27 citation statements)

References 84 publications

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“…holds promise with regard to gaining definitive insights into biological processes [123][124][125][126][127][128][129][130][131][132]. Both genomic [81,[133][134][135][136][137][138] and proteomic [115,[139][140][141][142][143] approaches have begun to yield insights into the mechanisms of the response to T/HS.…”

Section: Systems Biology Approaches Can Shed Insight Into Inflammatiomentioning

confidence: 99%

The Acute Inflammatory Response in Trauma /Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Namas¹,

Ghuma²,

Hermus

et al. 2008

Libyan Journal of Medicine

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Abstract; Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP's). DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future.

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Section: Systems Biology Approaches Can Shed Insight Into Inflammatiomentioning

confidence: 99%

The Acute Inflammatory Response in Trauma /Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Namas¹,

Ghuma²,

Hermus

et al. 2008

Libyan Journal of Medicine

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“…Recently, neuroproteomics has become a prominent means to assess neurodegenerative conditions, and it has been found to be particularly useful for biomarker discovery (Ekegren et al, 2008;Hanrieder et al, 2009;Kochanek et al, 2008;Ottens et al, 2006Ottens et al, , 2007Zetterberg et al, 2008;Zhang et al, 2008). A number of proteomic studies have examined TBI (Agoston et al, 2009;Gao et al, 2007;Haqqani et al, 2007;Hanrieder et al, 2009;Hergenroeder et al, 2008a;Jenkins et al, 2002;Kochanek et al, 2006;Ottens et al, 2007;Prieto et al, 2008), as well as brain ischemia (Chen et al, 2007Cid et al, 2007;Dhodda et al, 2004;Focking et al, 2006;Junker et al, 2007;Koh, 2009;Sung et al, 2009;Yao et al, 2008Zhang et al, 2009), a common component of TBI.…”

Section: Introductionmentioning

confidence: 99%

Neuroproteomics: A Biochemical Means To Discriminate the Extent and Modality of Brain Injury

Ottens

Bustamante

Golden

et al. 2010

Journal of Neurotrauma

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Diagnosis and treatment of stroke and traumatic brain injury remain significant health care challenges to society. Patient care stands to benefit from an improved understanding of the interactive biochemistry underlying neurotrauma pathobiology. In this study, we assessed the power of neuroproteomics to contrast biochemical responses following ischemic and traumatic brain injuries in the rat. A middle cerebral artery occlusion (MCAO) model was employed in groups of 30-min and 2-h focal neocortical ischemia with reperfusion. Neuroproteomes were assessed via tandem cation-anion exchange chromatography-gel electrophoresis, followed by reversed-phase liquid chromatography-tandem mass spectrometry. MCAO results were compared with those from a previous study of focal contusional brain injury employing the same methodology to characterize homologous neocortical tissues at 2 days post-injury. The 30-min MCAO neuroproteome depicted abridged energy production involving pentose phosphate, modulated synaptic function and plasticity, and increased chaperone activity and cell survival factors. The 2-h MCAO data indicated near complete loss of ATP production, synaptic dysfunction with degraded cytoarchitecture, more conservative chaperone activity, and additional cell survival factors than those seen in the 30-min MCAO model. The TBI group exhibited disrupted metabolism, but with retained malate shuttle functionality. Synaptic dysfunction and cytoarchitectural degradation resembled the 2-h MCAO group; however, chaperone and cell survival factors were more depressed following TBI. These results underscore the utility of neuroproteomics for characterizing interactive biochemistry for profiling and contrasting the molecular aspects underlying the pathobiological differences between types of brain injuries.

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“…Similar rigorous approaches have been successfully used in several other valuable and important neuroproteomics studies. 37,53 Western blot analysis Further validation was carried out to quantitatively detect the protein expression levels of four calcineurin subunits and isoforms. Western blot analysis was performed as previously described.…”

Section: Discussionmentioning

confidence: 99%

“…62,70 Mass spectrometry and 2D gel electrophoresis have been successfully employed to discover biomarkers in cerebrospinal fluid or serum from adult and pediatric TBI patients. 7,11,13,19,23,24,26,37,53,77,83 While the identification of biomarkers is important to bring novel tools to the diagnosis and management of recovery after TBI, these markers rarely provide insight into the underlying pathophysiological mechanisms of TBI.…”

Section: Introductionmentioning

confidence: 99%

Detection of Structural and Metabolic Changes in Traumatically Injured Hippocampus by Quantitative Differential Proteomics

Zhao

Haidacher

et al. 2013

Journal of Neurotrauma

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Traumatic brain injury (TBI) is a complex and common problem resulting in the loss of cognitive function. In order to build a comprehensive knowledge base of the proteins that underlie these cognitive deficits, we employed unbiased quantitative mass spectrometry, proteomics, and bioinformatics to identify and quantify dysregulated proteins in the CA3 subregion of the hippocampus in the fluid percussion model of TBI in rats. Using stable isotope 18 O-water differential labeling and multidimensional tandem liquid chromatography (LC)-MS/MS with high stringency statistical analyses and filtering, we identified and quantified 1002 common proteins, with 124 increased and 76 decreased. The Ingenuity Pathway Analysis (IPA) bioinformatics tool identified that TBI had profound effects on downregulating global energy metabolism, including glycolysis, the Krebs cycle, and oxidative phosphorylation, as well as cellular structure and function. Widespread upregulation of actin-related cytoskeletal dynamics was also found. IPA indicated a common integrative signaling node, calcineurin B1 (CANB1, CaNBa, or PPP3R1), which was downregulated by TBI. Western blotting confirmed that the calcineurin regulatory subunit, CANB1, and its catalytic binding partner PP2BA, were decreased without changes in other calcineurin subunits. CANB1 plays a critical role in downregulated networks of calcium signaling and homeostasis through calmodulin and calmodulin-dependent kinase II to highly interconnected structural networks dominated by tubulins. This large-scale knowledge base lays the foundation for the identification of novel therapeutic targets for cognitive rescue in TBI.

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Novel neuroproteomic approaches to studying traumatic brain injury

Cited by 45 publications

References 84 publications

The Acute Inflammatory Response in Trauma /Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

The Acute Inflammatory Response in Trauma /Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Neuroproteomics: A Biochemical Means To Discriminate the Extent and Modality of Brain Injury

Detection of Structural and Metabolic Changes in Traumatically Injured Hippocampus by Quantitative Differential Proteomics

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