Glial Fibrillary Acidic Protein (GFAP) Outperforms S100 Calcium-Binding Protein B (S100B) and Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) as Predictor for Positive Computed Tomography of the Head in Trauma Subjects

Mahan, Margaret Y.; Thorpe, Maxwell; Ahmadi, Aliya; Abdallah, Tessneem; Casey, Hannah; Sturtevant, Dylan; Judge-Yoakam, Sénait; Hoover, Caleb; Rafter, Daniel; Miner, James R.; Richardson, Chad J; Samadani, Uzma

doi:10.1016/j.wneu.2019.04.170

Cited by 44 publications

(48 citation statements)

References 59 publications

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“…GFAP, an astrocyte-specific intermediate filament released upon disruption of the blood-brain barrier, has shown the most promising results for detecting the presence of CT abnormalities in patients with TBI, distinguishing diffuse from focal brain injury, and predicting clinical outcome. 10,12,[18][19][20][21] S100B, another marker of glial injury, has been previously examined in multiple settings. However, we chose to examine GFAP over S100B based on the fact that elevations in S100B have been observed in patients with isolated extracranial injuries and thus it is subject to confounding in patients with multisystem injuries.…”

Section: Discussionmentioning

confidence: 99%

“…We conducted a secondary analysis of data collected from patients enrolled in the placebo arm of the "Prehospital Tranexamic Acid Use for Traumatic Brain Injury" trial, a Phase II, double-blind, multicenter randomized controlled trial (ClinicalTrials.gov NCT01990768). This study was designed to examine the efficacy and safety of prehospital administration of TXA compared to placebo in patients with MS-TBI [prehospital Glasgow Coma Scale (GCS) [3][4][5][6][7][8][9][10][11][12] who were not in shock (systolic blood pressure (SBP) > 90). Subjects were enrolled according to the Food and Drug Administration (FDA) "Exception from informed consent requirements for emergency research" (21CFR50.24).…”

Section: Methodsmentioning

confidence: 99%

“…9 In addition, the ability of biomarkers of structural brain injury to predict intracranial hemorrhage on radiographic studies has been increasingly demonstrated. [10][11][12][13][14] The growing evidence supporting the diagnostic and predictive value of circulating biomarkers for TBI supports further exploration of their clinical utility.…”

Section: Introductionmentioning

confidence: 99%

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Blood-based biomarkers for prediction of intracranial hemorrhage and outcome in patients with moderate or severe traumatic brain injury

Anderson

Hwang

Munar

et al. 2020

J Trauma Acute Care Surg

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Blood-based biomarkers for prediction of intracranial hemorrhage and outcome in patients with moderate or severe traumatic brain injury

Anderson

Hwang

Munar

et al. 2020

J Trauma Acute Care Surg

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“…blood-brain barrier opening and neuronal necrosis. For instance, recent work shows that GFAP has strong predictive power for brain injury following trauma, and is strongly associated with neurodegenerative disease and stroke 41 . With the 20 second dose consisting of 40 pulses, we did not observe reactive microglia or astrocyte reactivity in the predicted ultrasound focus, nor did we find neuroinflammation lateralized to the side of sonication, indicating focused damage.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences

Solarana

Rafi

et al. 2019

Sci Rep

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Exposure of the brain to high-intensity stress waves creates the potential for long-term functional deficits not related to thermal or cavitational damage. Possible sources of such exposure include overpressure from blast explosions or high-intensity focused ultrasound (HIFU). While current ultrasound clinical protocols do not normally produce long-term neurological deficits, the rapid expansion of potential therapeutic applications and ultrasound pulse-train protocols highlights the importance of establishing a safety envelope beyond which therapeutic ultrasound can cause neurological deficits not detectable by standard histological assessment for thermal and cavitational damage. In this study, we assessed the neuroinflammatory response, behavioral effects, and brain micro-electrocorticographic (µECoG) signals in mice following exposure to a train of transcranial pulses above normal clinical parameters. We found that the HIFU exposure induced a mild regional neuroinflammation not localized to the primary focal site, and impaired locomotor and exploratory behavior for up to 1 month post-exposure. In addition, low frequency (δ) and high frequency (β, γ) oscillations recorded by ECoG were altered at acute and chronic time points following HIFU application. ECoG signal changes on the hemisphere ipsilateral to HIFU exposure are of greater magnitude than the contralateral hemisphere, and persist for up to three months. These results are useful for describing the upper limit of transcranial ultrasound protocols, and the neurological sequelae of injury induced by high-intensity stress waves.

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“…Serum biomarkers offer potential to aid in objective measurement and prognostication of brain injury 11 , and have been examined in various brain injury cohorts including brain death. 12 In particular, glial fibrillary acidic protein (GFAP), the predominant filament protein in the astrocytic skeleton has demonstrated potential as a marker of astrocytic injury 3, 14 , and is markedly upregulated during astrogliosis, a process in which astrocytes increase in size and number in response to traumatic and anoxic injury. 15,16 Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a neuron-specific protein, known for its role in the addition and removal of ubiquitin from proteins.…”

Section: Introductionmentioning

confidence: 99%

Machine Learning with Objective Serum Markers and Algorithmic Deep Learning CT Scan Analysis Predicts Brain Death Due to Trauma and Hypoxia

Rafter

Sterk

et al. 2021

Preprint

Self Cite

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Objective: Brain death is a controversial construct because proving irreversible cessation of neurologic function is difficult, and ascertaining the timepoint at which irreversibility has occurred is not currently possible. The ability to predict which traumatic (TBI) and hypoxic brain injuries will progress to brain death is also limited. We investigated how accurately neurologic serum markers can predict brain death and differentiate its etiology. Methods: This prospective observational study enrolled brain injury subjects presenting to a trauma center within 32 hours of injury. Levels of glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 Calcium-Binding Protein B (S100B) were compared. Clinically brain dead (BD) subjects were further subdivided into high velocity trauma with presumed diffuse axonal injury (DAI), cardiopulmonary/respiratory arrest (CA/RA), and found down (FD). Results: The prognostic value of various biomarker combinations in identifying subjects progressing to brain death was assessed using machine learning. Prediction accuracy for GFAP, UCH-L1, and S100B in combination to predict brain death from among all other cohorts yielded an area under the curve (AUC) of 0.98 versus all other brain injury subjects. This model was also able to distinguish CA/RA BD from combined non-trauma controls and DAI BD with an AUC of 0.99. Conclusion: Serum concentrations of GFAP, UCH-L1, and S100B measured within 32 hours of traumatic and hypoxic brain injury have utility in prognosticating brain death by mechanism of injury as either hypoxic (CA/RA) or traumatic/unknown (DAI and FD).

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Glial Fibrillary Acidic Protein (GFAP) Outperforms S100 Calcium-Binding Protein B (S100B) and Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) as Predictor for Positive Computed Tomography of the Head in Trauma Subjects

Cited by 44 publications

References 59 publications

Blood-based biomarkers for prediction of intracranial hemorrhage and outcome in patients with moderate or severe traumatic brain injury

Blood-based biomarkers for prediction of intracranial hemorrhage and outcome in patients with moderate or severe traumatic brain injury

Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences

Machine Learning with Objective Serum Markers and Algorithmic Deep Learning CT Scan Analysis Predicts Brain Death Due to Trauma and Hypoxia

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