Cerebrospinal Fluid Biomarkers To Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury

Kwon, Brian K.; Streijger, Femke; Fallah, Nader; Noonan, Vanessa K.; Bélanger, Lise; Ritchie, Leanna; Paquette, Scott; Ailon, Tamir; Boyd, Michael; Street, John; Fisher, Charles G.; Dvorak, Marcel F.

doi:10.1089/neu.2016.4435

Cited by 119 publications

(111 citation statements)

References 56 publications

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“…An upregulation in systemic and local IP10 has been demonstrated in both human and rodent SCI [40,41,42], and while no time-matched controls were used, this upregulation persisted as long as 14 days post-SCI in the murine tSCI model. IP10, is a chemokine secreted by a wide array of immune cells, endothelial cells and fibroblasts in response to IFNg [43].…”

Section: Discussionmentioning

confidence: 99%

Level-Specific Differences in Systemic Expression of Pro- and Anti-Inflammatory Cytokines and Chemokines after Spinal Cord Injury

Hong

Chang

Zavvarian

et al. 2018

IJMS

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While over half of all spinal cord injuries (SCIs) occur in the cervical region, the majority of preclinical studies have focused on models of thoracic injury. However, these two levels are anatomically distinct—with the cervical region possessing a greater vascular supply, grey-white matter ratio and sympathetic outflow relative to the thoracic region. As such, there exists a significant knowledge gap in the secondary pathology at these levels following SCI. In this study, we characterized the systemic plasma markers of inflammation over time (1, 3, 7, 14, 56 days post-SCI) after moderate-severe, clip-compression cervical and thoracic SCI in a rat model. Using high-throughput ELISA panels, we observed a clear level-specific difference in plasma levels of VEGF, leptin, IP10, IL18, GCSF, and fractalkine. Overall, cervical SCI had reduced expression of both pro- and anti-inflammatory proteins relative to thoracic SCI, likely due to sympathetic dysregulation associated with higher level SCIs. However, contrary to the literature, we did not observe level-dependent splenic atrophy with our incomplete SCI model. This is the first study to compare the systemic plasma-level changes following cervical and thoracic SCI using level-matched and time-matched controls. The results of this study provide the first evidence in support of level-targeted intervention and also challenge the phenomenon of high SCI-induced splenic atrophy in incomplete SCI models.

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Section: Discussionmentioning

confidence: 99%

Level-Specific Differences in Systemic Expression of Pro- and Anti-Inflammatory Cytokines and Chemokines after Spinal Cord Injury

Hong

Chang

Zavvarian

et al. 2018

IJMS

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“…(2016) confirmed that CSF GFAP concentrations were higher in complete vs. incomplete SCI 427 patients and hence that GFAP concentrations appear to be associated with SCI severity (9,73). …”

mentioning

confidence: 88%

The developing landscape of diagnostic and prognostic biomarkers for spinal cord injury in cerebrospinal fluid and blood

Fuller

et al. 2016

Spinal Cord

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“…114 Several neurotrauma biomarkers have been previously combined to evaluate patients with CNS injuries. 16,91,115 Unsupervised factor analysis is typically used for psychological scores aiding in cognitive assessment of TBI patients. 116,117 To our knowledge, this is the first study to apply EFA on a new small neurotrauma biomarker panel that revealed kinetic differences.…”

Section: Aid Biomarker Panel Uniqueness and Significance For Future Tmentioning

confidence: 99%

New astroglial injury-defined biomarkers for neurotrauma assessment

Halford

Shen

Itamura

et al. 2017

J Cereb Blood Flow Metab

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Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs. Their levels increased over four orders of magnitude in severe TBI CSF. First post-injury week, ALDOC levels were markedly high and stable. Short-lived BLBP and PEA15 related to injury progression. ALDOC, BLBP and PEA15 appeared hyper-acutely and were similarly robust in severe and mild TBI blood; 25kD-GFAP-BDP appeared overnight after TBI and was rarely present after mild TBI. Using a human culture trauma model, we investigated biomarker kinetics. Wounded (mechanoporated) astrocytes released ALDOC, BLBP and PEA15 acutely. Delayed cell death corresponded with GFAP release and proteolysis into small GFAP-BDPs. Associating biomarkers with cellular injury stages produced astroglial injury-defined (AID) biomarkers that facilitate TBI assessment, as neurological deficits are rooted not only in death of CNS cells, but also in their functional compromise.

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Cerebrospinal Fluid Biomarkers To Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury

Cited by 119 publications

References 56 publications

Level-Specific Differences in Systemic Expression of Pro- and Anti-Inflammatory Cytokines and Chemokines after Spinal Cord Injury

Level-Specific Differences in Systemic Expression of Pro- and Anti-Inflammatory Cytokines and Chemokines after Spinal Cord Injury

The developing landscape of diagnostic and prognostic biomarkers for spinal cord injury in cerebrospinal fluid and blood

New astroglial injury-defined biomarkers for neurotrauma assessment

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