Extracellular vesicle neurofilament light is elevated within the first 12-months following traumatic brain injury in a U.S military population.

Traumatic brain injury (TBI) can be associated with long-term neurobehavioral symptoms. Here, we examined levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in extracellular vesicles isolated from blood, and their relationship with TBI severity and neurobehavioral symptom reporting. Participants were 218 service members and veterans who sustained uncomplicated mild TBIs (mTBI, n = 107); complicated mild, moderate, or severe TBIs (smcTBI, n = 66); or Injured controls (IC, orthopedic injury without TBI, n = 45). Within one year after injury, but not after, NfL was higher in the smcTBI group than mTBI (p = 0.001, d = 0.66) and IC (p = 0.001, d = 0.35) groups, which remained after controlling for demographics and injury characteristics. NfL also discriminated the smcTBI group from IC (AUC:77.5%, p < 0.001) and mTBI (AUC:76.1%, p < 0.001) groups. No other group differences were observed for NfL or GFAP at either timepoint. NfL correlated with post-concussion symptoms (rs = - 0.38, p = 0.04) in the mTBI group, and with PTSD symptoms in mTBI (rs = - 0.43, p = 0.021) and smcTBI groups (rs = - 0.40, p = 0.024) within one year after injury, which was not confirmed in regression models. Our results suggest the potential of NfL, a protein previously linked to axonal damage, as a diagnostic biomarker that distinguishes TBI severity within the first year after injury.

Survival Rates and Biomarkers in a Large Animal Model of Traumatic Brain Injury Combined With Two Different Levels of Blood Loss.

INTRODUCTION: The pathology resulting from concurrent traumatic brain injury (TBI) and hemorrhagic shock (HS; TBI+HS) are leading causes of mortality and morbidity worldwide following trauma. However, the majority of large animal models of TBI+HS have utilized focal/contusional injuries rather than incorporating the types of brain trauma (closed-head injury caused by dynamic acceleration) that typify human injury. OBJECTIVE: To examine survival rates and effects on biomarkers from rotational TBI with two levels of HS. METHODS: Twenty-two sexually mature Yucatan swine (30.39 ±â€Š2.25 kg; 11 females) therefore underwent either Sham trauma procedures (n = 6) or a dynamic acceleration TBI combined with either 55% (n = 8) or 40% (n = 8) blood loss in this serial study. RESULTS: Survival rates were significantly higher for the TBI+40% (87.5%) relative to TBI+55% (12.5%) cohort, with the majority of TBI+55% animals expiring within 2 h post-trauma from apnea. Blood-based neural biomarkers and immunohistochemistry indicated evidence of diffuse axonal injury (increased NFL/Aß42), blood-brain barrier breach (increased immunoglobulin G) and inflammation (increased glial fibrillary acidic protein/ionized calcium-binding adaptor molecule 1) in the injured cohorts relative to Shams. Invasive hemodynamic measurements indicated increased shock index and decreased pulse pressure in both injury cohorts, with evidence of partial recovery for invasive hemodynamic measurements in the TBI+40% cohort. Similarly, although both injury groups demonstrated ionic and blood gas abnormalities immediately postinjury, metabolic acidosis continued to increase in the TBI+55% group ∼85 min postinjury. Somewhat surprisingly, both neural and physiological biomarkers showed significant changes within the Sham cohort across the multi-hour experimental procedure, most likely associated with prolonged anesthesia. CONCLUSION: Current results suggest the TBI+55% model may be more appropriate for severe trauma requiring immediate medical attention/standard fluid resuscitation protocols whereas the TBI+40% model may be useful for studies of prolonged field care.

Circulating Brain Injury Exosomal Proteins following Moderate-To-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications.

Brain injury exosomal proteins are promising blood biomarker candidates in traumatic brain injury (TBI). A better understanding of their role in the diagnosis, characterization, and management of TBI is essential for upcoming clinical implementation. In the current investigation, we aimed to explore longitudinal trajectories of brain injury exosomal proteins in blood of patients with moderate-to-severe TBI, and to evaluate the relation with the free-circulating counterpart and patient imaging and clinical parameters. Exosomal levels of glial (glial fibrillary acidic protein (GFAP)) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), and total-tau (t-tau)) proteins were measured in serum of 21 patients for up 5 days after injury using single molecule array (Simoa) technology. Group-based trajectory analysis was used to generate distinct temporal exosomal biomarker profiles. We found altered profiles of serum brain injury exosomal proteins following injury. The dynamics and levels of exosomal and related free-circulating markers, although correlated, showed differences. Patients with diffuse injury displayed higher acute exosomal NFL and GFAP concentrations in serum than those with focal lesions. Exosomal UCH-L1 profile characterized by acutely elevated values and a secondary steep rise was associated with early mortality (n = 2) with a sensitivity and specificity of 100%. Serum brain injury exosomal proteins yielded important diagnostic and prognostic information and represent a novel means to unveil underlying pathophysiology in patients with moderate-to-severe TBI. Our findings support their utility as potential tools to improve patient phenotyping in clinical practice and therapeutic trials.