Biomarkers in traumatic brain injury: a review

Toman, Emma; Harrisson, Stuart; Belli, Tony

doi:10.1136/jramc-2015-000517

Cited by 34 publications

(36 citation statements)

References 69 publications

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“…2) must be considered where simultaneous changes in composition and tail phosphorylation levels are observed. Such changes, for example, occur during neuronal growth and development, following injury, and in neurodegenerative diseases (8,11,46). Specifically, our results indicate a close relation of phosphorylation and NF compression response and orientation, which was scarcely considered before (6).…”

Section: Discussionmentioning

confidence: 65%

Phosphorylation-Induced Mechanical Regulation of Intrinsically Disordered Neurofilament Proteins

Malka-Gibor

Kornreich

Laser-Azogui

et al. 2017

Biophysical Journal

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The biological function of protein assemblies has been conventionally equated with a unique three-dimensional protein structure and protein-specific interactions. However, in the past 20 years it has been found that some assemblies contain long flexible regions that adopt multiple structural conformations. These include neurofilament proteins that constitute the stress-responsive supportive network of neurons. Herein, we show that the macroscopic properties of neurofilament networks are tuned by enzymatic regulation of the charge found on the flexible protein regions. The results reveal an enzymatic (phosphorylation) regulation of macroscopic properties such as orientation, stress response, and expansion in flexible protein assemblies. Using a model that explains the attractive electrostatic interactions induced by enzymatically added charges, we demonstrate that phosphorylation regulation is far richer and versatile than previously considered.

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Section: Discussionmentioning

confidence: 65%

Phosphorylation-Induced Mechanical Regulation of Intrinsically Disordered Neurofilament Proteins

Malka-Gibor

Kornreich

Laser-Azogui

et al. 2017

Biophysical Journal

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“…Brain derived proteins (such as S100B, GFAP and NSE) do not cross BBB in individuals with an intact BBB . Blood levels of these proteins have been used as a marker for brain injury with BBB disruption .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, multiple factors such as hyperglycaemia, matrix metalloproteinase activity and insulin administration are associated with increased BBB permeability . S100B, GFAP and NSE are shown to increase following both traumatic and DKA associated brain injury . However, it is still not clear whether S100B and NSE proteins expressed in CNS enter into circulation as a result of disrupted BBB in trauma patients, or they increase because of increased expression by peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

Brain injury markers: S100 calcium-binding protein B, neuron-specific enolase and glial fibrillary acidic protein in children with diabetic ketoacidosis

et al. 2018

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NSE and GFAP levels do not increase in DKA patients without overt brain injury. Elevated levels of S100B, which is also synthesized from non-neuronal tissues, might arise from peripheral sources. A lack of concurrent increase in serum levels of these brain injury markers might result from the yet intact blood brain barrier or a true absence of neuronal damage. In order to reveal subclinical brain injury related to DKA, there is a need for studies concurrently assessing neurocognitive functions.

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“…Previous studies have determined that there is an association between the severity of the inflammatory response to heart surgery and an increased need for medical intervention or length of stay at hospitals (20,21,39–43). The current study hypothesized that newborns with CHD and in whom circulating pro-inflammatory mediators and complements were elevated, would have measureable concentrations of CNS-derived proteins, indicative of a compromised BBB and CNS injury.…”

Section: Introductionmentioning

confidence: 99%

“…The current study hypothesized that newborns with CHD and in whom circulating pro-inflammatory mediators and complements were elevated, would have measureable concentrations of CNS-derived proteins, indicative of a compromised BBB and CNS injury. Serum markers of brain injury (43) include the high molecular weight (200 kDa) neurofilament protein (NF-H) that is abundant in neurons and concentrated in axons. The highly phosphorylated form of NF (pNF-H) is resistant to proteolysis and when released from damaged axons remains largely intact; thus, its presence in the blood is indicative of neuronal damage (44,45).…”

Section: Introductionmentioning

confidence: 99%

Brain injury with systemic inflammation in newborns with congenital heart disease undergoing heart surgery

Pironkova

Giamelli

Seiden

et al. 2017

Experimental and Therapeutic Medicine

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The potential role of systemic inflammation on brain injury in newborns with congenital heart disease (CHD) was assessed by measuring levels of central nervous system (CNS)-derived proteins in serum prior to and following cardiac surgery. A total of 23 newborns (gestational age, 39±1 weeks) with a diagnosis of CHD that required cardiac surgery with cardiopulmonary bypass (CPB) were enrolled in the current study. Serum samples were collected immediately prior to surgery and 2, 24 and 48 h following CPB, and serum levels of phosphorylated neurofilament-heavy subunit (pNF-H), neuron-specific enolase (NSE) and S100B were analyzed. Systemic inflammation was assessed by measuring serum concentrations of complement C5a and complement sC5b9, and the following cytokines: Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL12p70, interferon γ and tumor necrosis factor (TNF)-α. Analysis of cord blood from normal term deliveries (n=26) provided surrogate normative values for newborns. pNF-H and S100B were 2.4- to 2.8-fold higher (P<0.0001) in patient sera than in cord blood prior to surgery and remained elevated following CPB. Pre-surgical serum pNF-H and S100B levels directly correlated with interleukin (IL)-12p70 (ρ=0.442, P<0.05). pNF-H was inversely correlated with arterial pO2 prior to surgery (ρ=−0.493, P=0.01) and directly correlated with arterial pCO2 post-CPB (ρ=0.426, P<0.05), suggesting that tissue hypoxia and inflammation contribute to blood brain barrier (BBB) dysfunction and neuronal injury. Serum IL12p70, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher in patients than in normal cord blood and levels of these cytokines increased following CPB (P<0.001). Activation of complement was observed in all patients prior to surgery, and serum C5a and sC5b9 remained elevated up to 48 h post-surgery. Furthermore, they were correlated (P<0.05) with low arterial pO2, high pCO2 and elevated arterial pressure in the postoperative period. Length of mechanical ventilation was associated directly with post-surgery serum IL-12p70 and IL-8 concentrations (P<0.05). Elevated serum concentrations of pNF-H and S100B in neonates with CHD suggest BBB dysfunction and CNS injury, with concurrent hypoxemia and an activated inflammatory response potentiating this effect.

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Biomarkers in traumatic brain injury: a review

Cited by 34 publications

References 69 publications

Phosphorylation-Induced Mechanical Regulation of Intrinsically Disordered Neurofilament Proteins

Phosphorylation-Induced Mechanical Regulation of Intrinsically Disordered Neurofilament Proteins

Brain injury markers: S100 calcium-binding protein B, neuron-specific enolase and glial fibrillary acidic protein in children with diabetic ketoacidosis

Brain injury with systemic inflammation in newborns with congenital heart disease undergoing heart surgery

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