Journal of neurotrauma
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Journal of neurotrauma · Sep 2018
Cerebral Blood Flow Velocities and Functional Outcomes in Pediatric Mild Traumatic Brain Injury.
Outcomes can be challenging to predict in children with mild traumatic brain injury (TBI). Transcranial Doppler (TCD) ultrasound has become an increasingly useful modality in adult and pediatric TBI by measuring blood flow velocities within the circle of Willis. In children with moderate-to-severe TBI, multiple studies have correlated abnormal TCD measurements and poor outcomes. ⋯ Although our data did not show correlation, it showed that the investigation could feasibly be done in pediatric patients with mild TBI. The study was limited by small sample size and infrequent outcome of interest. Future studies may help define the role of TCD in the large population of mild pediatric TBI patients.
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Journal of neurotrauma · Sep 2018
Randomized Controlled Trials in Adult Traumatic Brain Injury: A Systematic Review on the Use and Reporting of Clinical Outcome Assessments.
As part of efforts to improve study design, the use of outcome measures in randomized controlled trials (RCTs) in traumatic brain injury (TBI) is receiving increasing attention. This review aimed to assess how clinical outcome assessments (COAs) have been used and reported in RCTs in adult TBI. Systematic literature searches were conducted to identify medium to large (n ≥ 100) acute and post-acute TBI trials published since 2000. ⋯ The use of PROs was limited, especially in acute study settings. Quality of reporting was variable, and key information concerning COAs was often omitted, making it difficult to know how precisely outcomes were assessed. Consistency across studies would be increased and future meta-analyses facilitated by (a) using common data elements (CDEs) recommendations for TBI outcomes and (b) following CONSORT guidelines when publishing RCTs.
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Journal of neurotrauma · Sep 2018
Traumatic Brain Injury-Induced Acute Lung Injury: Evidence for Activation and Inhibition of a Neural-Respiratory-Inflammasome Axis.
Approximately 20-25% of traumatic brain injury (TBI) subjects develop acute lung injury (ALI), but the pathomechanisms of TBI-induced ALI remain poorly defined. Our previous work has shown that the inflammasome plays a critical role in TBI-induced secondary pathophysiology and that inflammasome proteins are released in extracellular vesicles (EV) after TBI. Here we investigated whether EV-mediated inflammasome signaling contributed to the etiology of TBI-induced ALI. ⋯ We show that TBI releases EV containing inflammasome proteins into serum that target the lung to cause ALI, supporting activation of a neural-respiratory-inflammasome axis. Administration of a low-molecular-weight heparin (enoxaparin, a blocker of EV uptake) or treatment with a monoclonal antibody against apoptosis speck-like staining protein containing a caspase recruitment domain (anti-ASC) after adoptive transfer of EV isolated from TBI-injured mice significantly inhibited inflammasome activation in the lungs of recipient mice resulting in improved ALI scores. This axis constitutes an important arm of the innate inflammatory response in lung pathology after TBI and targeting this axis represents a novel therapeutic treatment for TBI-induced ALI.
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Journal of neurotrauma · Sep 2018
FGF21 Protects the Blood-Brain Barrier by Upregulating PPARγ via FGFR1/β-klotho after Traumatic Brain Injury.
Blood-brain barrier (BBB) disruption and dysfunction result in brain edema, which is responsible for more than half of all deaths after severe traumatic brain injury (TBI). Fibroblast growth factor 21 (FGF21) has a potential neuroprotective function in the brain. However, the effects and underlying possible mechanism of action on BBB integrity following TBI remain unknown. ⋯ In addition, the specific FGFR1 and peroxisome proliferator-activated receptor gamma (PPARγ) inhibitors PD173074 and GW9662, respectively, were applied to further explore the possible mechanism of rhFGF21 in BBB maintenance after TBI. rhFGF21 markedly reduced neurofunctional behavior deficits and cerebral edema degree, preserved BBB integrity, and recued brain tissue loss and neuron apoptosis in the mouse model after TBI. Both in vivo and in vitro, rhFGF21 upregulated TJ and AJ proteins, thereby preserving the BBB. Moreover, rhFGF21 activated PPARγ in TNF-α-induced HBMECs through formation of an FGF21/FGFR1/β-klotho complex. rhFGF21 protected the BBB through FGF21/FGFR1/β-klotho complex formation and PPARγ activation, which upregulated TJ and AJ proteins.
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Journal of neurotrauma · Sep 2018
A Systematic Review of Positron Emission Tomography of Tau, Amyloid Beta, and Neuroinflammation in Chronic Traumatic Encephalopathy: The Evidence To Date.
Chronic traumatic encephalopathy (CTE) is associated with pathological changes, yet detecting these changes during life has proven elusive. Positron emission tomography (PET) offers the potential for identifying such pathology. Few studies have been completed to date and their approaches and results have been diverse. ⋯ Evidence for increased uptake in cortical regions was less consistent. The evidence suggests that the field of PET imaging in those at risk for CTE remains nascent. As the field evolves to include more stringent studies, ligands for PET may prove an important tool in identifying CTE in vivo.