Light-Guided Percutaneous Neck Rejuvenation With Division of Platysma Bands and Suture Suspension: A Multicenter Retrospective Study.

BACKGROUND: Traditional invasive suture suspension techniques have proven efficacy and durability. A previously described percutaneous placement of a neck suspension suture with light guidance has transformed this into a minimally invasive technique. This novel technique provides a major advance for minimally invasive neck rejuvenation. OBJECTIVES: The authors sought to describe their experience with light-guided percutaneous neck rejuvenation over the past 4.5 years, including technique, patient selection, safety profile, and expected outcomes. METHODS: Data were retrospectively reviewed for all patients who underwent the procedure with 5 surgeons across 4 aesthetic plastic surgery practices from January 2018 through May 2022. Inclusion criteria were mild to moderate neck laxity, prominent anterior platysma bands, and desire to improve neck contour. Patients undergoing concurrent skin incision >5 mm (ie, open rhytidectomy or platysmaplasty) were excluded. RESULTS: A total of 391 patients meeting criteria were identified during the study period. No hematomas were documented. Four patients (1%) developed infection at the suture site, 1 resolving on antibiotics and 3 requiring suture removal. Eighteen (4.6%) developed recurrent platysmal bands, and 7 (1.8%) had residual loose skin. Four (1%) experienced transient marginal mandibular neuropraxia. Mean length of follow-up time was 240 days. CONCLUSIONS: Light-guided percutaneous suture suspension is a safe and viable option for improving neck contours. Although it does not address extensive skin laxity or excess submental fat, it can be combined with energy-based tissue tightening, submental liposuction, or skin excision. In selected patients, this minimally invasive procedure provides predictable results with a low risk of complications.

Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle-Aged and Older Adults.

BACKGROUND: Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level. METHODS AND RESULTS: Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants. Linear regression analyses were conducted to test the cross-sectional associations of each miRNA with 8 CVD risk factors. Prospective analyses of the associations of miRNAs with new-onset obesity, hypertension, type 2 diabetes, CVD, and all-cause mortality were conducted using proportional hazards regression. Replication was carried out in 1999 RS (Rotterdam Study) participants. Pathway enrichment analyses were conducted and target genes were predicted for miRNAs associated with ≥5 risk factors in the FHS. In the FHS, 6 miRNAs (miR-193b-3p, miR-122-5p, miR-365a-3p, miR-194-5p, miR-192-5p, and miR-193a-5p) were associated with ≥5 risk factors. This miRNA signature was enriched for pathways associated with CVD and several genes annotated to these pathways were predicted targets of the identified miRNAs. Furthermore, miR-193b-3p, miR-194-5p, and miR-193a-5p were each associated with ≥2 risk factors in the RS. Prospective analysis revealed 8 miRNAs associated with all-cause mortality in the FHS. CONCLUSIONS: These findings highlight associations between miRNAs and CVD risk factors that may provide valuable insights into the underlying pathogenesis of CVD.

The percutaneous trampoline platysmaplasty: technique and experience with 105 consecutive patients.

BACKGROUND: Controversy persists regarding the optimal procedure to rejuvenate the aging neck. More invasive procedures carry increased risks of complications, whereas less invasive approaches may deliver marginal results. The challenge is selecting the appropriate procedure for delivering consistent, durable results meeting both the patient's and surgeon's expectations. OBJECTIVES: The authors describe their trampoline platysmaplasty (TPP) approach, a percutaneous suture suspension necklift that constitutes a less invasive approach for neck rejuvenation. METHODS: A retrospective study was conducted of 105 consecutive patients who underwent TPP. Age, sex, procedure(s) performed, complications, and patient satisfaction were recorded. Cadaver studies were conducted to compare the tensile strength of the ligaments that anchor the TPP to the tensile strength of the sutures placed to approximate the medial platysma borders. In addition, the accuracy of light transillumination to determine depth of travel of the light-emitting diode (LED) lighted rod was evaluated. RESULTS: Patients underwent either TPP alone (18 women, 24 men) or TPP with a facelift (35 women, 28 men) between October 2007 and June 2009. The average age of the patients was 52 years, and average length of follow-up was 33 months. Patient satisfaction was high. Three early patients underwent immediate revision to improve results secondary to the suture matrix being too loose. Six additional patients had recurrent banding around one year postoperatively, but correction was achieved in all six by replacing the matrix with the help of the lighted rod. The results of the cadaver study revealed that the tensile strength of the retaining ligaments was statistically identical to the medial platysma borders, and the light transillumination feedback was accurate with regard to the depth of travel of the illuminated rod tip. CONCLUSIONS: The TPP approach for neck rejuvenation is effective and durable in properly-selected patients. It works well as a stand-alone procedure and in conjunction with facelift procedures. It also offers younger patients a less-invasive option to improve neck contours inherited through genetics. After nearly three years of follow-up of the patients in this report, the results appear to be long-lasting.

New Horizons in Imaging and Diagnosis in Rhinoplasty.

Three-dimensional (3D) surface imaging has found its place in aesthetic surgery globally. The first attempt to use 3D surface imaging technique in clinic was in 1944 by Thalmaan, who used stereo photogrammetry to examine an adult with facial asymmetry and a baby with Pierre Robin syndrome. Three-dimensional photography is becoming more common allowing for a more dynamic facial evaluation, although it is associated with increased cost.

Tau Is Elevated in Pediatric Patients on Extracorporeal Membrane Oxygenation.

Neurologic injury is a known and feared complication of extracorporeal membrane oxygenation (ECMO). Neurologic biomarkers may have a role in assisting in early identification of such. Axonal biomarker tau has not been investigated in the pediatric ECMO population. The objective of this study is to evaluate plasma levels of tau in pediatric patients supported with ECMO. Eighteen patients requiring ECMO support in a quaternary pediatric intensive care unit at a university-affiliated children's hospital from October 2015 to February 2017 were enrolled. Patients undergoing extracorporeal cardiopulmonary resuscitation or recent history of bypass were excluded. Plasma tau was measured using enzyme-linked immunosorbent assay. Neuroimaging was reviewed for acute neurologic injury, and tau levels were analyzed to assess for correlation. Tau was significantly higher in ECMO patients than in control subjects. Sixty-one percent of subjects had evidence of acute brain injury on neuroimaging, but tau level did not correlate with injury. Subjects with multifocal injury all experienced infarction and had significantly higher tau levels on ECMO day 3 than patients with isolated injury. In addition, peak tau levels of neuro-injured subjects were compared with controls and noninjured ECMO subjects using receiver operating curve analysis. This study demonstrates preliminary evidence of axonal injury in pediatric ECMO patients.

In vitro synthesis of arachidonoyl amino acids by cytochrome c.

Arachidonoyl amino acids are a class of endogenous lipid messengers that are expressed in the mammalian central nervous system and peripherally. While several of their prominent pharmacologic effects have been documented, the mechanism by which arachidonoyl amino acids are biosynthesized has not been defined. We have previously observed that the mitochondrial protein, cytochrome c, is capable of catalyzing the formation of the prototypic arachidonoyl amino acid, arachidonoyl glycine, utilizing arachidonoyl CoA and glycine as substrates, in the presence of hydrogen peroxide. Here we report that cytochrome c is similarly able to catalyze the formation of N-arachidonoyl serine, N-arachidonoyl alanine, and N-arachidonoyl gamma aminobutyric acid from arachidonoyl CoA and the respective amino acids. The identities of the arachidonoyl amino acid products were verified by mass spectral fragmentation pattern analysis. The synthetic reactions exhibited Michaelis-Menten kinetics and continued favorably at physiologic temperature and pH. Spectral data indicate that both cytochrome c protein structure and a +3 heme iron oxidation state are required for the reaction mechanism to proceed optimally. Reactions designed to catalyze the formation of N-arachidonoyl dopamine were not efficient due to the rapid oxidation of dopamine substrate by hydrogen peroxide, consuming both reactants. Finally, under standard assay conditions, arachidonoyl CoA and ethanolamine were found to react spontaneously to form anandamide, independent of cytochrome c and hydrogen peroxide. Accordingly, it was not possible to demonstrate a potential role for cytochrome c in the biosynthetic mechanism for either arachidonoyl dopamine or anandamide. However, the ability of cytochrome c to effectively catalyze the formation of N-arachidonoyl serine, N-arachidonoyl alanine, and N-arachidonoyl gamma aminobutyric acid in vitro highlights its potential role for the generation of these lipid messengers in vivo.

Radiation resistance of normal human astrocytes: the role of non-homologous end joining DNA repair activity.

Radiotherapy is a common modality for treatment of brain cancers, but it can induce long-term physiological and cognitive deficits. The responses of normal human brain cells to radiation is not well understood. Astrocytes have been shown to have a variety of protective mechanisms against oxidative stress and have been shown to protect neurons. We investigated the response of cultured normal human astrocytes (NHAs) to X-ray irradiation. Following exposure to 10 Gy X-irradiation, NHAs exhibited DNA damage as indicated by the formation of γ-H2AX foci. Western blotting showed that NHAs displayed a robust increase in expression of non-homologous end joining DNA repair enzymes within 15 min post-irradiation and increased expression of homologous recombination DNA repair enzymes ~2 h post-irradiation. The cell cycle checkpoint protein p21/waf1 was upregulated from 6-24 h, and then returned to baseline. Levels of DNA repair enzymes returned to basal ~48 h post-irradiation. NHAs re-entered the cell cycle and proliferation was observed at 6 days. In contrast, normal human mesenchymal stem cells (MSCs) failed to upregulate DNA repair enzymes and instead displayed sustained upregulation of p21/waf1, a cell cycle checkpoint marker for senescence. Ectopic overexpression of Ku70 was sufficient to protect MSCs from sustained upregulation of p21/waf1 induced by 10 Gy X-rays. These findings suggest that increased expression of Ku70 may be a key mechanism for the radioresistance of NHAs, preventing their accelerated senescence from high-dose radiation. These results may have implications for the development of novel targets for radiation countermeasure development.

α-Amidated Peptides: Approaches for Analysis.

α-Amidation is a terminal modification in peptide biosynthesis that can itself be rate limiting in the overall production of bioactive α-amidated peptides. More than half of the known neural and endocrine peptides are α-amidated and in most cases this structural feature is essential for receptor recognition, signal transduction, and thus biologic function. This chapter describes methods for developing and using analytical tools to study the biology of α-amidated peptides. The principal analytical method used to quantify α-amidated peptides is the radioimmunoassay (RIA). Detailed protocols are provided for (1) primary antibody production and characterization; (2) radiolabeling of RIA peptides; (3) sample preparation; and (4) performance of the RIA itself. Techniques are also described for the identification and verification of α-amidated peptides. Lastly, in vivo models used for studying the biology of α-amidation are discussed.

Cytochrome c catalyzes the in vitro synthesis of arachidonoyl glycine.

Long chain fatty acyl glycines are an emerging class of biologically active molecules that occur naturally and produce a wide array of physiological effects. Their biosynthetic pathway, however, remains unknown. Here we report that cytochrome c catalyzes the synthesis of N-arachidonoyl glycine (NAGly) from arachidonoyl coenzyme A and glycine in the presence of hydrogen peroxide. The identity of the NAGly product was verified by isotope labeling and mass analysis. Other heme-containing proteins, hemoglobin and myoglobin, were considerably less effective in generating arachidonoyl glycine as compared to cytochrome c. The reaction catalyzed by cytochrome c in vitro points to its potential role in the formation of NAGly and other long chain fatty acyl glycines in vivo.

alpha-Amidated peptides: approaches for analysis.

alpha-Amidation is a terminal modification in peptide biosynthesis that can itself be rate-limiting in the overall production of bioactive alpha-amidated peptides. More than half of the known neural and endocrine peptides are alpha-amidated and in most cases, this structural feature is essential for receptor recognition, signal transduction, and thus, biologic function. This chapter describes methods for developing and using analytical tools to study the biology of alpha-amidated peptides. The principle analytical method used to quantify alpha-amidated peptides is the radioimmunoassay (RIA). Detailed protocols are provided for 1) primary antibody production and characterization; 2) radiolabeling of RIA peptides; 3) sample preparation; and 4) the performance of the RIA itself. Techniques are also described for the identification and verification of alpha-amidated peptides. Lastly, in vivo models used for studying the biology of alpha-amidation are discussed.

Mechanisms of Endogenous Neuroprotective Effects of Astrocytes in Brain Injury.

Astrocytes, once believed to serve only as "glue" for the structural support of neurons, have been demonstrated to serve critical functions for the maintenance and protection of neurons, especially under conditions of acute or chronic injury. There are at least seven distinct mechanisms by which astrocytes protect neurons from damage; these are (1) protection against glutamate toxicity, (2) protection against redox stress, (3) mediation of mitochondrial repair mechanisms, (4) protection against glucose-induced metabolic stress, (5) protection against iron toxicity, (6) modulation of the immune response in the brain, and (7) maintenance of tissue homeostasis in the presence of DNA damage. Astrocytes support these critical functions through specialized responses to stress or toxic conditions. The detoxifying activities of astrocytes are essential for maintenance of the microenvironment surrounding neurons and in whole tissue homeostasis. Improved understanding of the mechanisms by which astrocytes protect the brain could lead to the development of novel targets for the development of neuroprotective strategies.

The Effects of Blast Exposure on Protein Deimination in the Brain.

Oxidative stress and calcium excitotoxicity are hallmarks of traumatic brain injury (TBI). While these early disruptions may be corrected over a relatively short period of time, long-lasting consequences of TBI including impaired cognition and mood imbalances can persist for years, even in the absence of any evidence of overt injury based on neuroimaging. This investigation examined the possibility that disordered protein deimination occurs as a result of TBI and may thus contribute to the long-term pathologies of TBI. Protein deimination is a calcium-activated, posttranslational modification implicated in the autoimmune diseases rheumatoid arthritis and multiple sclerosis, where aberrant deimination creates antigenic epitopes that elicit an autoimmune attack. The present study utilized proteomic analyses to show that blast TBI alters the deimination status of proteins in the porcine cerebral cortex. The affected proteins represent a small subset of the entire brain proteome and include glial fibrillary acidic protein and vimentin, proteins reported to be involved in autoimmune-based pathologies. The data also indicate that blast injury is associated with an increase in immunoglobulins in the brain, possibly representing autoantibodies directed against novel protein epitopes. These findings indicate that aberrant protein deimination is a biomarker for blast TBI and may therefore underlie chronic neuropathologies of head injury.

Murine atrial HL-1 cells express highly active peptidylglycine alpha-amidating enzyme.

Peptidylglycine-alpha-hydroxylating monooxygenase (PHM; EC 1.14.17.3) catalyzes the rate limiting step in peptide alpha-amidation, a posttranslational modification that is essential for receptor recognition and signal transduction. Secretory granules of the cardiac atrium contain the highest natural concentration of PHM and clearly demonstrate regulation of PHM expression and activity. The HL-1 atrial myocyte cell line faithfully maintains the differentiated phenotype of native atrial cells and thus provides an in vitro model system for investigating the mechanisms that regulate PHM. We observed that the specific activity of PHM expressed in HL-1 cells is five times higher than that found in rat atrium. The increased activity of HL-1 cell PHM was not reflected by a difference in Km for peptide substrate, change in copper optimum, altered sensitivity to inactivation by suicide inhibitor or variance in response to limited proteolysis by trypsin. Additionally, mixing experiments indicated that the increased activity in HL-1 cells versus rat atrium was not due to a diffusible factor. Based upon these findings we propose that the increased Vmax of HL-1 cell PHM results from a structural or conformational difference that involves either differential posttranslational modification and/or a high affinity chaperone that serves to regulate enzymatic activity by protein-protein interaction. The mechanism involved may participate in physiologic regulation of PHM.

In vivo evidence that N-oleoylglycine acts independently of its conversion to oleamide.

Oleamide (cis-9-octadecenamide) is a member of an emerging class of lipid-signaling molecules, the primary fatty acid amides. A growing body of evidence indicates that oleamide mediates fundamental neurochemical processes including sleep, thermoregulation, and nociception. Nevertheless, the mechanism for oleamide biosynthesis remains unknown. The leading hypothesis holds that oleamide is synthesized from oleoylglycine via the actions of the peptide amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The present study investigated this hypothesis using pharmacologic treatments, physiologic assessments, and measurements of serum oleamide levels using a newly developed enzyme-linked immunosorbant assay (ELISA). Oleamide and oleoylglycine both induced profound hypothermia and decreased locomotion, over equivalent dose ranges and time courses, whereas, closely related compounds, stearamide and oleic acid, were essentially without effect. While the biologic actions of oleamide and oleoylglycine were equivalent, the two compounds differed dramatically with respect to their effects on serum levels of oleamide. Oleamide administration (80mg/kg) elevated blood-borne oleamide by eight-fold, whereas, the same dose of oleoylglycine had no effect on circulating oleamide levels. In addition, pretreatment with the established PAM inhibitor, disulfiram, produced modest reductions in the hypothermic responses to both oleoylglycine and oleamide, suggesting that the effects of disulfiram were not mediated through inhibition of PAM and a resulting decrease in the formation of oleamide from oleoylglycine. Collectively, these findings raise the possibilities that: (1) oleoylglycine possesses biologic activity that is independent of its conversion to oleamide and (2) the increased availability of oleoylglycine as a potential substrate does not drive the biosynthesis of oleamide.

Proteomic analysis of rat atrial secretory granules: a platform for testable hypotheses.

The recent development of powerful proteomic tools has enabled investigators to directly examine the population of proteins present in defined biological systems. We report here the first proteomic analysis of atrial secretory granules. Approximately 100 distinct protein components of the atrial secretory granule proteome were detected using subcellular fractionation and one-dimensional SDS-PAGE in conjunction with peptide mass fingerprinting by MALDI-TOF mass spectrometry. Of this number, 61 proteins were clearly identified by high probability data matches and repeated observation. The majority of the proteome was found to be membrane-associated with the most prominent proteins being peptidylglycine alpha-amidating monooxygenase (PAM) and pro-atrial natriuretic peptide (pro-ANP). This proteomic analysis of the rat atrium secretory granule produced an assembly of proteins with a diverse array of reported functions. The identified proteins fall into seven functional categories: (1) granular transport, docking and fusion; (2) signal transduction; (3) calcium-binding/calcium-dependent; (4) cellular architecture/chaperoning; (5) peptide/protein processing; (6) hormone; (7) proton transport. The novel finding of several protein processing enzymes and signal transduction proteins offer new perspectives on how pro-ANP is stored and processed to ANP during release. Accordingly, defining the proteome of the atrial secretory granule provides a framework for the development of new hypotheses that address key mechanisms governing granule function and ANP secretion.

Protein carbonylation after traumatic brain injury: cell specificity, regional susceptibility, and gender differences.

Protein carbonylation is a well-documented and quantifiable consequence of oxidative stress in several neuropathologies, including multiple sclerosis, Alzheimer׳s disease, and Parkinson׳s disease. Although oxidative stress is a hallmark of traumatic brain injury (TBI), little work has explored the specific neural regions and cell types in which protein carbonylation occurs. Furthermore, the effect of gender on protein carbonylation after TBI has not been studied. The present investigation was designed to determine the regional and cell specificity of TBI-induced protein carbonylation and how this response to injury is affected by gender. Immunohistochemistry was used to visualize protein carbonylation in the brains of adult male and female Sprague-Dawley rats subjected to controlled cortical impact (CCI) as an injury model of TBI. Cell-specific markers were used to colocalize the presence of carbonylated proteins in specific cell types, including astrocytes, neurons, microglia, and oligodendrocytes. Results also indicated that the injury lesion site, ventral portion of the dorsal third ventricle, and ventricular lining above the median eminence showed dramatic increases in protein carbonylation after injury. Specifically, astrocytes and limited regions of ependymal cells adjacent to the dorsal third ventricle and the median eminence were most susceptible to postinjury protein carbonylation. However, these patterns of differential susceptibility to protein carbonylation were gender dependent, with males showing significantly greater protein carbonylation at sites distant from the lesion. Proteomic analyses were also conducted and determined that the proteins most affected by carbonylation in response to TBI include glial fibrillary acidic protein, dihydropyrimidase-related protein 2, fructose-bisphosphate aldolase C, and fructose-bisphosphate aldolase A. Many other proteins, however, were not carbonylated by CCI. These findings indicate that there is both regional and protein specificity in protein carbonylation after TBI. The marked increase in carbonylation seen in ependymal layers distant from the lesion suggests a mechanism involving the transmission of a cerebral spinal fluid-borne factor to these sites. Furthermore, this process is affected by gender, suggesting that hormonal mechanisms may serve a protective role against oxidative stress.

Protein Citrullination: A Proposed Mechanism for Pathology in Traumatic Brain Injury.

Protein citrullination is a calcium-driven post-translational modification proposed to play a causative role in the neurodegenerative disorders of Alzheimer's disease, multiple sclerosis (MS), and prion disease. Citrullination can result in the formation of antigenic epitopes that underlie pathogenic autoimmune responses. This phenomenon, which is best understood in rheumatoid arthritis, may play a role in the chronic dysfunction following traumatic brain injury (TBI). Despite substantial evidence of aberrations in calcium signaling following TBI, there is little understanding of how TBI alters citrullination in the brain. The present investigation addressed this gap by examining the effects of TBI on the distribution of protein citrullination and on the specific cell types involved. Immunofluorescence revealed that controlled cortical impact in rats profoundly up--regulated protein citrullination in the cerebral cortex, external capsule, and hippocampus. This response was exclusively seen in astrocytes; no such effects were observed on the status of protein citrullination in neurons, oligodendrocytes or microglia. Further, proteomic analyses demonstrated that the effects of TBI on citrullination were confined to a relatively small subset of neural proteins. Proteins most notably affected were those also reported to be citrullinated in other disorders, including prion disease and MS. In vivo findings were extended in an in vitro model of simulated TBI employing normal human astrocytes. Pharmacologically induced calcium excitotoxicity was shown to activate the citrullination and breakdown of glial fibrillary acidic protein, producing a novel candidate TBI biomarker and potential target for autoimmune recognition. In summary, these findings demonstrate that the effects of TBI on protein citrullination are selective with respect to brain region, cell type, and proteins modified, and may contribute to a role for autoimmune dysfunction in chronic pathology following TBI.

Protein Oxidation in the Lungs of C57BL/6J Mice Following X-Irradiation.

Damage to normal lung tissue is a limiting factor when ionizing radiation is used in clinical applications. In addition, radiation pneumonitis and fibrosis are a major cause of mortality following accidental radiation exposure in humans. Although clinical symptoms may not develop for months after radiation exposure, immediate events induced by radiation are believed to generate molecular and cellular cascades that proceed during a clinical latent period. Oxidative damage to DNA is considered a primary cause of radiation injury to cells. DNA can be repaired by highly efficient mechanisms while repair of oxidized proteins is limited. Oxidized proteins are often destined for degradation. We examined protein oxidation following 17 Gy (0.6 Gy/min) thoracic X-irradiation in C57BL/6J mice. Seventeen Gy thoracic irradiation resulted in 100% mortality of mice within 127-189 days postirradiation. Necropsy findings indicated that pneumonitis and pulmonary fibrosis were the leading cause of mortality. We investigated the oxidation of lung proteins at 24 h postirradiation following 17 Gy thoracic irradiation using 2-D gel electrophoresis and OxyBlot for the detection of protein carbonylation. Seven carbonylated proteins were identified using mass spectrometry: serum albumin, selenium binding protein-1, alpha antitrypsin, cytoplasmic actin-1, carbonic anhydrase-2, peroxiredoxin-6, and apolipoprotein A1. The carbonylation status of carbonic anhydrase-2, selenium binding protein, and peroxiredoxin-6 was higher in control lung tissue. Apolipoprotein A1 and serum albumin carbonylation were increased following X-irradiation, as confirmed by OxyBlot immunoprecipitation and Western blotting. Our findings indicate that the profile of specific protein oxidation in the lung is altered following radiation exposure.

Blood Biomarkers in Moderate-To-Severe Traumatic Brain Injury: Potential Utility of a Multi-Marker Approach in Characterizing Outcome.

BACKGROUND: Blood biomarkers are valuable tools for elucidating complex cellular and molecular mechanisms underlying traumatic brain injury (TBI). Profiling distinct classes of biomarkers could aid in the identification and characterization of initial injury and secondary pathological processes. This study characterized the prognostic performance of a recently developed multi-marker panel of circulating biomarkers that reflect specific pathogenic mechanisms including neuroinflammation, oxidative damage, and neuroregeneration, in moderate-to-severe TBI patients. MATERIALS AND METHODS: Peripheral blood was drawn from 85 isolated TBI patients (n = 60 severe, n = 25 moderate) at hospital admission, 6-, 12-, and 24-h post-injury. Mortality and neurological outcome were assessed using the extended Glasgow Outcome Scale. A multiplex platform was designed on MULTI-SPOT(®) plates to simultaneously analyze human plasma levels of s100 calcium binding protein beta (s100B), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), brain-derived neurotrophic factor (BDNF), monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-5, and peroxiredoxin (PRDX)-6. Multivariable logistic regression and area under the receiver-operating characteristic curve (AUC) were used to evaluate both individual and combined predictive abilities of these markers for 6-month neurological outcome and mortality after TBI. RESULTS: Unfavorable neurological outcome was associated with elevations in s100B, GFAP, and MCP-1. Mortality was related to differences in six of the seven markers analyzed. Combined admission concentrations of s100B, GFAP, and MCP-1 were able to discriminate favorable versus unfavorable outcome (AUC = 0.83), and survival versus death (AUC = 0.87), although not significantly better than s100B alone (AUC = 0.82 and 0.86, respectively). CONCLUSION: The multi-marker panel of TBI-related biomarkers performed well in discriminating unfavorable and favorable outcomes in the acute period after moderate-to-severe TBI. However, the combination of these biomarkers did not outperform s100B alone.

Autoimmune Profiling Reveals Peroxiredoxin 6 as a Candidate Traumatic Brain Injury Biomarker.

Autoimmune profiling in rats revealed the antioxidant enzyme, peroxiredoxin 6 (PRDX6), as a target for autoantibodies evoked in response to traumatic brain injury (TBI). Consistent with this proposal, immunohistochemical analysis of rat cerebral cortex demonstrated that PRDX6 is highly expressed in the perivascular space, presumably contained within astrocytic foot processes. Accordingly, an immunosorbent electrochemiluminescence assay was developed for investigating PRDX6 in human samples. PRDX6 was found to be measurable in human blood and highly expressed in human cerebral cortex and platelets. Circulating levels of PRDX6 were elevated fourfold over control values 4 to 24 h following mild-to-moderate TBI. These findings suggest that PRDX6 may serve as a biomarker for TBI and that autoimmune profiling is a viable strategy for the discovery of novel TBI biomarkers.