Cerebrospinal Fluid and Microdialysis Cytokines in Severe Traumatic Brain Injury: A Scoping Systematic Review

Zeiler, Frederick A.; Thelin, Eric Peter; Czosnyka, Marek; Hutchinson, Peter J.; Menon, David; Helmy, Adel

doi:10.3389/fneur.2017.00331

Cited by 67 publications

(55 citation statements)

References 62 publications

(212 reference statements)

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“…We also investigated changes in protein expression overtime in athletes that had received a single concussion. Our data showed significant changes in MCP-1 (also known as CCL2), which is one of the most well correlated TBI proteins [35,50]. MCP-1 has been shown to be expressed in the CNS by astrocytes [51,52].…”

Section: Discussionmentioning

confidence: 77%

“…The secondary inflammatory response following concussion is regulated by pro-and anti-inflammatory cytokines [21,22]. Expression patterns of these cytokines is associated with the different forms and severity of TBI [29,35]. In our study we were able to assess variances in the expression of 92 circulating inflammatory proteins in athletes suffering from repetitive concussions within a three-month period.…”

Section: Discussionmentioning

confidence: 96%

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Differential Expression of Circulating Inflammatory Proteins Following Sport-Related Traumatic Brain Injury

Begum¹,

Reddy

Yakoub

et al. 2020

IJMS

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Sport-related traumatic brain injury (TBI) elicits a multifaceted inflammatory response leading to brain injury and morbidity. This response could be a predictive tool for the progression of TBI and to stratify the injury of which mild TBI is most prevalent. Therefore, we examined the differential expression of serum inflammatory markers overtime and identified novel markers in repetitively concussed athletes. Neuropsychological assessment by Wechsler Adult Intelligence Scale (WAIS) and Immediate Post Concussion Assessment and Cognitive Test (ImPACT) was performed on rugby players and serum was taken from healthy, concussed and repetitively concussed athletes. Serum was also obtained <1 week and >1 week after trauma and analyzed for 92 inflammatory protein markers. Fibroblast growth factor 21 (FGF21) and interleukin-7 (IL-7) differentiated repetitively concussed athletes. Macrophage chemotactic protein-1 (MCP-1), tumor necrosis factor superfamily member 14 (TNFSF14) were significantly reduced >1 week and chemokine (C-X3-C motif) ligand 1 (CX3CL1) upregulated <1 week after injury. FGF21 and MCP-1 negatively correlated with symptoms and their severity. We have identified dynamic changes in the inflammatory response overtime and in different classes of concussion correlating with disease progression. This data supports the use of inflammatory biomarkers as predictors of symptom development due to secondary complications of sport-related mTBI. mTBI can be defined as head trauma resulting in either memory loss or altered neurological function up to a day following the traumatic ictus or loss of consciousness for under 30 min [5]. A large proportion of mTBI consists of sport-related concussive (SRC) injury with up to 3.8 million cases reported in the United States annually [6]. There is also a greater risk of these athletes experiencing repetitive concussions which has been associated with the development of neurodegenerative diseases such as Parkinson's, Alzheimer's, and chronic traumatic encephalopathy (CTE) [6][7][8][9][10][11][12][13][14][15]. Neurocognitive tests have been developed to diagnose concussion. However, these assessments are expensive, subject to bias due to lack of appropriate baselines and have not yet demonstrated efficacy as prognostic tools [16][17][18].Difficulties in developing tools for the prediction of progressive pathology in TBI are confounded by the variability in the anatomical location, extent of the mechanical injury to the brain, as well as the multitude of biological response mechanisms involved. TBI is broadly characterized by 2 phases [19,20]. Immediately after impact, the primary phase is associated with shearing and tearing of neural and vascular brain structures and enhanced permeability of the blood-brain barrier. Within minutes start the secondary phase, where danger-associated molecular pattern (DAMPs) molecules are released from damaged cells which stimulate the Toll-like receptor (TLR) [21]. Cytokines and chemokines are also released leading to the recruitment of microglia a...

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 96%

Differential Expression of Circulating Inflammatory Proteins Following Sport-Related Traumatic Brain Injury

Begum¹,

Reddy

Yakoub

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…In recent years CMD has been used as part of NCC monitoring and to study biomarkers of various neurological diseases in particular traumatic brain injury (28)(29)(30), gliomas (31,32), ischemic stroke(1), intracerebral hemorrhage (33) and subarachnoid hemorrhage (34,35). CMD sampling for subsequent proteomic biomarker analysis has advantages, such as capture of proteins near the site of origin in the extracellular space, and no effect of dilution as is the case in CSF or plasma (28).…”

Section: Discussionmentioning

confidence: 99%

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

Tobieson

Czifra

Wåhlén

et al. 2020

Preprint

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Background: Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue. Methods: In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal. Results: We found unique protein patterns in the molecular weight range of 10-35 kDa for each of the three compartments. Conclusion: This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.

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“…98 This suggests that the extracranial injury burden is not necessarily an additional driver of impaired vascular reactivity, but the individual systemic stress response to trauma may drive impaired cerebrovascular reactivity. These findings raise questions as to the role of the autonomic nervous system, 52,54,99 inflammatory mediators, 59,100,101 and TBI therapeutic interventions (e.g. deep sedation, fluids, cooling, transfusion) 7,10,11,102 in the acute phase, in driving impaired autoregulation in TBI.…”

Section: Association With Patient and Injury Factorsmentioning

confidence: 99%

Continuous cerebrovascular reactivity monitoring in moderate/severe traumatic brain injury: a narrative review of advances in neurocritical care

Zeiler

Ercole

Czosnyka

et al. 2020

British Journal of Anaesthesia

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Impaired cerebrovascular reactivity in adult moderate and severe traumatic brain injury (TBI) is known to be associated with worse global outcome at 6e12 months. As technology has improved over the past decades, monitoring of cerebrovascular reactivity has shifted from intermittent measures, to experimentally validated continuously updating indices at the bedside. Such advances have led to the exploration of individualised physiologic targets in adult TBI management, such as optimal cerebral perfusion pressure (CPP) values, or CPP limits in which vascular reactivity is relatively intact. These targets have been shown to have a stronger association with outcome compared with existing consensus-based guideline thresholds in severe TBI care. This has sparked ongoing prospective trials of such personalised medicine approaches in adult TBI. In this narrative review paper, we focus on the concept of cerebral autoregulation, proposed mechanisms of control and methods of continuous monitoring used in TBI. We highlight multimodal cranial monitoring approaches for continuous cerebrovascular reactivity assessment, physiologic and neuroimaging correlates, and associations with outcome. Finally, we explore the recent 'state-of-the-art' advances in personalised physiologic targets based on continuous cerebrovascular reactivity monitoring, their benefits, and implications for future avenues of research in TBI.

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Cerebrospinal Fluid and Microdialysis Cytokines in Severe Traumatic Brain Injury: A Scoping Systematic Review

Cited by 67 publications

References 62 publications

Differential Expression of Circulating Inflammatory Proteins Following Sport-Related Traumatic Brain Injury

Differential Expression of Circulating Inflammatory Proteins Following Sport-Related Traumatic Brain Injury

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

Continuous cerebrovascular reactivity monitoring in moderate/severe traumatic brain injury: a narrative review of advances in neurocritical care

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