Biomarkers Of Brain Damage Research Articles

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI.

Plasma neurofilament light chain (NF-L) levels were assessed as a diagnostic biomarker for traumatic brain injury (TBI) and as a prognostic biomarker for somatomotor recovery, cognitive decline, and epileptogenesis. Rats with severe TBI induced by lateral fluid-percussion injury (n = 26, 13 with and 13 without epilepsy) or sham-operation (n = 8) were studied. During a 6-month follow-up, rats underwent magnetic resonance imaging (MRI) (day (D) 2, D7, and D21), composite neuroscore (D2, D6, and D14), Morris-water maze (D35−D39), and a 1-month-long video-electroencephalogram to detect unprovoked seizures during the 6th month. Plasma NF-L levels were assessed using a single-molecule assay at baseline (i.e., naïve animals) and on D2, D9, and D178 after TBI or a sham operation. Plasma NF-L levels were 483-fold higher on D2 (5072.0 ± 2007.0 pg/mL), 89-fold higher on D9 (930.3 ± 306.4 pg/mL), and 3-fold higher on D176 32.2 ± 8.9 pg/mL after TBI compared with baseline (10.5 ± 2.6 pg/mL; all p < 0.001). Plasma NF-L levels distinguished TBI rats from naïve animals at all time-points examined (area under the curve [AUC] 1.0, p < 0.001), and from sham-operated controls on D2 (AUC 1.0, p < 0.001). Plasma NF-L increases on D2 were associated with somatomotor impairment severity (ρ = −0.480, p < 0.05) and the cortical lesion extent in MRI (ρ = 0.401, p < 0.05). Plasma NF-L increases on D2 or D9 were associated with the cortical lesion extent in histologic sections at 6 months post-injury (ρ = 0.437 for D2; ρ = 0.393 for D9, p < 0.05). Plasma NF-L levels, however, did not predict somatomotor recovery, cognitive decline, or epileptogenesis (p > 0.05). Plasma NF-L levels represent a promising noninvasive translational diagnostic biomarker for acute TBI and a prognostic biomarker for post-injury somatomotor impairment and long-term structural brain damage.

Difference in GFAP Levels in POCD and Non-POCD Patients After on Pump CABG.

On-pump, coronary artery bypass grafting (CABG) is the most common cause of postoperative cognitive dysfunction (POCD) after cardiac surgery. Previous studies showed that the incidence of POCD after cardiac surgery was 60%, higher than non-cardiac surgery with 11.7%. Glial fibrillary acid protein (GFAP) is one of the sensitive biomarkers of brain damage. Previous studies have found that elevated GFAP serum is associated with cognitive impairment. This study aims to measure the difference in GFAP levels in POCD and non-POCD patients after CABG on-pump surgery. This study is a retrospective cohort design study. The data were obtained from 56 subjects undergoing elective CABG on the pump surgery enrolled into two groups consisting of 28 POCD as a case group and 28 non-POCD as a control group. In this study, the ELISA method measured the levels of GFAP biomarkers within 24 hours after surgery. After 72 hours, the patient received a MoCA-INA examination to determine cognitive impairment. Data analysis was carried out by SPSS 23.00 software. The mean age of patients in both groups was 60 years and was dominated by males (>85%). POCD patients were found to have a significantly longer duration of cardiopulmonary bypass (CPB) and cross-clamp surgery than non-POCD patients (p = 0.002 and p = 0.004). Postoperative GFAP levels in POCD patients were significantly higher than in non-POCD patients (12.95 ± 7.47 vs 3.80 ± 2.77, p < 0.001). There was a significant increase in GFAP levels compared with non-POCD (8.28 ± 7.24 vs -1.5 ± 3.03, p < 0.001). The area under the curve (AUC) value of GFAP against POCD was 0.887, cut-off GFAP 4.750 with a sensitivity of 92.9% and a specificity of 71.4%. POCD patients had higher GFAP levels than non-POCD patients. There are differences in GFAP levels in patients with POCD and non-POCD post-CABG surgery.

The role of neuron-specific enolase (NSE) and S100B protein in the incidence of acute postoperative cognitive dysfunction (POCD) in geriatric patients receiving general anesthesia

Introduction: Postoperative cognitive dysfunction (POCD) following general anesthesia is frequent among geriatric patients worldwide. Neuroinflammation and neuronal injury have been associated with the incidence of POCD. Some biomarkers of brain damage including neuron-specific enolase (NSE) and S100B protein have been widely studied; however, their association with the incidence of POCD is still controversial. This study aimed to assess the correlation of serum NSE and S100B levels with the incidence of POCD among geriatric patients receiving general anesthesia. Methods: A prospective cohort study was conducted among geriatric patients receiving general anesthesia at Dr. Soetomo Hospital, Surabaya from July to October 2022. The Montreal Cognitive Assessment (MoCA) INA instrument was used to assess POCD, and enzyme-linked immunosorbent assay (ELISA) was used to quantify the levels of serum NSE and S100B. Spearman’s rank correlation was implemented to identify the correlation of MoCA INA scores with the levels of NSE and S100B. Mann-Whitney analysis was used to determine the association between NSE and S100B levels with the incidence of POCD. A p-value of ≤0.05 was considered statistically significant. Results: A total of 48 patients were enrolled in the study and 16.7% of them had POCD. Spearman’s correlation test suggested no significant correlation between MoCA INA score with serum NSE level (rs:-0.095; p=0.522) and S100B level (rs:-0.213; p=0.146). Mann-Whitney analysis indicated no significant difference in the NSE and S100B levels of patients with and without POCD (p=0.3470 and p=0.097, respectively). Conclusion: There was no significant association between NSE and S100B levels with the incidence of POCD among geriatric patients receiving general anesthesia during elective surgeries at Dr. Soetomo Hospital, Surabaya.

The Usefulness of Serum Brain Damage Biomarkers in Detection and Evaluation of Hypoxic Ischemic Encephalopathy in Calves with Perinatal Asphyxia.

The purpose of the present study was to determine hypoxic brain damage in calves with perinatal asphyxia using brain-specific damage biomarkers. Ten healthy and 25 calves with perinatal asphyxia were enrolled in the study. Clinical examination, neurological status score, and laboratory analysis were performed at admission, 24, 48, and 72 h. Serum concentrations of ubiquitin carboxy-terminal hydrolysis 1 (UCHL1), calcium-binding protein B (S100B), adrenomodullin (ADM), activitin A (ACTA), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and creatine kinase-brain (CK-B) were measured. Histopathological and immunohistochemical examinations of the brain tissue were performed in 13 nonsurvivor calves. The neurological status score of the calves with asphyxia was significantly (p < 0.05) lower. Mix metabolic-respiratory acidosis and hypoxemia were detected in calves with asphyxia. Serum UCHL1 and S100B were significantly (p < 0.05) increased, and NSE, ACTA, ADM, and CK-B were decreased (p < 0.05) in calves with asphyxia. Histopathological and immunohistochemical examinations confirmed the development of mild to severe hypoxic-ischemic encephalopathy. In conclusion, asphyxia and hypoxemia caused hypoxic-ischemic encephalopathy in perinatal calves. UCHL1 and S100B concentrations were found to be useful markers for the determination of hypoxic-ischemic encephalopathy in calves with perinatal asphyxia. Neurological status scores and some blood gas parameters were helpful in mortality prediction.

Bronchopulmonary dysplasia is not related to neurofilament light for neuroaxonal damage in preterm infants.

Neurofilament light (NfL) has been identified as a biomarker for neuroaxonal damage in preterm infants, but its relation with bronchopulmonary dysplasia (BPD) has not been established. We hypothesized that BPD is associated with increased NfL levels at an early stage, indicative of early neuroaxonal damage. We included preterm infants born <30 weeks of gestation for assessment of NfL levels from cord blood and blood obtained at postnatal days 3, 7, 14, and 28. We used linear regression analysis to compare NfL levels between infants with moderate/severe BPD and infants with no/mild BPD, and linear mixed model analysis to compare the effect of time on NfL levels between groups. Sixty-seven infants with a gestational age (GA) of 27 ± 1.3 weeks were included for analysis, of whom 19 (28%) developed moderate/severe BPD. Although NfL levels were higher at every time point in infants with BPD, statistical significance was lost after adjustment for GA, small for gestational age (SGA) and intraventricular hemorrhage (IVH). Groups did not differ in NfL change over time. The positive association between BPD and NfL in the first weeks of life could be explained by GA, SGA and IVH rather than by development of BPD. Neurofilament light chain (NfL) is a known biomarker for neuroaxonal damage. Biomarkers for brain damage during the first weeks of life in preterm infants developing BPD are lacking. NfL levels obtained during the first weeks of life did not differ between infants with and without BPD in analyses adjusted for GA, SGA, and IVH.

Early predictors of abnormal MRI patterns in asphyxiated infants: S100B protein urine levels.

The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the "gold standard" methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI. Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7-10days of life. Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions. High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment.

Increased Neuron Specific Enolase in a Hypoxic Ischemia Rat Model

Introduction: Acute brain injury caused by cerebral ischemia, either due to stroke or ischemic hypoxic-ischemic encephalopathy (HIE), represents a major neurological cause of death and disability worldwide. Neuronal cell injury has been shown to correlate with a significant increase in neuron-specific enolase (NSE) levels in in vitro studies. This study aims to measure NSE levels in the blood serum of rats with HIE. Methods: This study used an experimental post-test design in which occlusion of the right common carotid artery (CCA) was performed on Wistar rats, which were then placed in a hypoxic chamber and reperfused after 60 minutes (treatment group). Neurological scores were collected over the first 24 hours. After 48 hours, experimental animals were sacrificed and their serum NSE levels were measured using ELISA. Statistical analysis using a T-test was performed for independent samples. Results: A total of 16 male rats were included in the study. Neurological scores indicated that all HIE group rats experienced hemiparesis to varying degrees. NSE levels in the treatment group were significantly higher than in the control group (p &lt; 0.05). The mean NSE level in the treatment group was higher than that in the other group. Conclusion: Consistent with in vitro studies, we found that NSE was higher in the HIE rat model than in controls. These data support future studies to assess the fitness of serum NSE as a biomarker of brain damage.

Новейшие достижения в диагностике гипоксической ишемической энцефалопатии новорожденных

The prognosis in neonatal hypoxic ischemic encephalopathy (HIE) depends on early differential diagnosis for justified administration of emergency therapeutic hypothermia. The moment of therapy initiation directly affects the long-term neurological outcome: the earlier the commencement, the better the prognosis. This review analyzes recent advances in systems biology that facilitate early differential diagnosis of HIE as a pivotal complement to clinical indicators. We discuss the possibilities of clinical translation for proteomic, metabolomic and extracellular vesicle patterns characteristic of HIE and correlations with severity and prognosis. Identification and use of selective biomarkers of brain damage in neonates during the first hours of life is hindered by systemic effects of hypoxia. Chromatography– mass spectrometry blood tests allow analyzing hundreds and thousands of metabolites in a small biological sample to identify characteristic signatures of brain damage. Clinical use of advanced analytical techniques will facilitate the accurate and timely diagnosis of HIE for enhanced management.

Lutein levels in arterial cord blood correlate with neurotrophic calcium binding S100B protein in healthy preterm and term newborns

BackgroundS100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns.MethodsWe conducted a prospective study on the distribution of LT and S100B in arterial cord blood of healthy preterm (n = 50) and term (n = 50) newborns.ResultsS100B and LT showed a pattern of concentration characterized by higher levels (P < 0.01, for all) at 33-36 weeks gestation (GA) followed by a progressive decrease (P < 0.01, for all) from 37 onwards with a dip at term. Both S100B and LT were gender-dependent with significantly (P < 0.01, for all) higher levels in females in preterm and term groups. S100B (R = 0.68; P < 0.001) and LT (R = 0.40; P = 0.005) correlated with GA at sampling. A positive significant correlation (R = 0.87; P < 0.001) between S100B and LT was found.ConclusionsThe present data showing a correlation between S100B and LT supports the notion of a LT trophic role in the CNS. Further investigations in high-risk infants are needed to elucidate LT involvement in the pathophysiological cascade of events leading to CNS development and damage.

Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure.

AimsCognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF.Methods and resultsUsing bead‐based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters‐HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty‐six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = −4.7; P < 0.001), alanine aminotransferase (T = −2.1; P = 0.036), and the left atrial end‐systolic volume index (T = 3.4; P = 0.004). NT‐proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = −3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025).ConclusionsSerum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.

Oxidative Stress and Indicators of Brain Damage Following Pediatric Heart Surgery.

Pediatric cardiac surgery induces an increased oxidative stress (OS) response. Increased OS is associated with poor neurologic outcomes in neonatal populations with similar patterns of brain injury. We investigated OS and brain injury in infants undergoing heart surgery. Patients 6 months or younger, undergoing cardiac surgery with or without cardiopulmonary bypass (CPB), were included in this prospective, observational study. Patients were divided into infant (30 days–6 months) and neonatal (<30 days) groups for analysis. Urine OS biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α) was quantified pre-surgery and at 0 and 24 h post-surgery. A serum brain damage biomarker S100B protein was also measured pre-surgery and at 0 and 72 h post-surgery. Amplitude-integrated electroencephalography during surgery was analyzed. Neuropsychological evaluation using the Bayley III or Vineland test was performed in all patients at 24 months of age. Sixty-two patients were included, 44 of whom underwent follow-up neurologic evaluation. 8-iso-PGF2α and S100B levels were increased after surgery. Postoperative levels of S100B were positively correlated with 8-iso-PGF2α levels 24 h after surgery (rho = 0.5224; p = 0.0261). There was also a correlation between immediate post-surgery levels of 8-iso-PGF2α and intra-surgery seizure burden (rho = 0.4285, p = 0.0205). Patients with an abnormal neurological evaluation had increased levels of S100B 72 h after surgery (p = 0.048). 8-iso-PGF2α levels 24 h after surgery were also related to abnormal neurologic outcomes. Levels of 8-iso-PGF2α following pediatric cardiac surgery are associated with several indicators of brain injury including brain damage biomarkers, intra-operative seizures, and abnormal neurological evaluation at follow-up, suggesting the importance of oxidative stress response in the origin of brain damage in this population.

Metabolomics analysis reveals how water extract of Gastrodia elata helps against heroin addiction

To investigate the metabolomics changes and potential metabolic mechanisms of water extract of Gastrodia elata (WGE) in the treatment of heroin addicted mice. Sixty male Kunming mice were randomly divided into four groups as control group (n = 10), heroin addicted group (n = 10), natural withdrawal group (n = 10), and GE treatment group (500, 1000, 2000 mg/kg, n = 30). Heroin addicted group were injected subcutaneously in the 13 days with increased dosage from 3 mg/kg to 30 mg/kg. The control group was injected with the same amount of saline in the same manner. After 13 days of heroin administration, the treatment groups were given GE by gavage for a week. The natural withdrawal group was injected with the same amount of saline in the same manner. The metabolites were determined using ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). The scatting diagrams were plotted based on orthogonal partial least squares discrimination analysis (OPLS-DA). Potential differential metabolites were obtained using the combination of variable important in projection (VIP) and p value methods. Their metabolic pathways were analyzed using databases such as METLIN, HMDB, KEGG and metaboanalyst 5.0. The GE treatment group (500 mg/kg) could significantly reduce the withdrawal symptoms induced by heroin addiction and significantly improve the weight loss of heroin addicted mice. The metabolomics results showed that GE could regulate the levels of 30 different metabolites in heroin addicted mice, which mainly involved in the metabolism of Glutamic acid, Glutathione and Purine. The water extract of Gastrodia elata in the treatment of heroin addiction was confirmed for the first time in this study. The metabolomics analysis demonstrated that the metabolic disorder of endogenous substances changes from pretreatment to posttreatment. The potential biomarkers of brain damage may be feasible to elucidate its metabolic mechanisms.

The effect of clopidogrel and aspirin on the severity of traumatic brain injury in a rat model

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability worldwide. Aspirin (ASA) and clopidogrel (CLOP) are antiplatelet agents that inhibit platelet aggregation. They are implicated in worsening the intracerebral haemorrhage (ICH) risk post-TBI. However, antiplatelet drugs may also exert a neuroprotective effect post-injury. We determined the impact of ASA and CLOP treatment, alone or in combination, on ICH and brain damage in an experimental rat TBI model. We assessed changes in platelet aggregation and measured serum thromboxane by enzyme immune assay. We also explored a panel of brain damage and apoptosis biomarkers by immunoblotting. Rats were treated with ASA and/or CLOP for 48 h prior to TBI and sacrificed 48 h post-injury. In rats treated with antiplatelet agents prior to TBI, platelet aggregation was completely inhibited, and serum thromboxane was significantly decreased, compared to the TBI group without treatment. TBI increases UCHL-1 and GFAP, but decreases hexokinase expression compared to the non-injured controls. All groups treated with antiplatelet drugs prior to TBI had decreased UCH-L1 and GFAP serum levels compared to the TBI untreated group. Furthermore, the ASA and CLOP single treatments increased the hexokinase serum levels. We confirmed that αII-spectrin cleavage increased post-TBI, with the highest cleavage detected in CLOP-treated rats. Aspirin and/or CLOP treatment prior to TBI is a double-edged sword that exerts a dual effect post-injury. On one hand, ASA and CLOP single treatments increase the post-TBI ICH risk, with a further detrimental effect from the ASA + CLOP treatment. On the other hand, ASA and/or CLOP treatments are neuroprotective and result in a favourable profile of TBI injury markers. The ICH risk and the neuroprotection benefits from antiplatelet therapy should be weighed against each other to ameliorate the management of TBI patients.

Value of brain damage biomarkers in cerebrospinal fluid in neonates with hypoxic-ischemic brain injury.

Hypoxic-ischemic encephalopathy is one of the leading causes of death and neurological disability worldwide. A key issue in neonates with hypoxic-ischemic encephalopathy is accurately establishing the occurrence and severity of brain lesions soon after a perinatal hypoxic-ischemic event. This is crucial to help with prognosis; guide clinical decision-making, including the use of other therapies; and improve family counseling. Neurobiochemical markers may offer a quantitative approximation for estimating the severity of brain damage and identifying infants who have a high risk of further neurological disability. In addition, they should help identify those neonates who would benefit most from the implementation of other neuroprotective and neuroreparative interventions. Despite considerable progress in this area, relatively few studies have been aimed at examining the clinical utility of brain-specific proteins in cerebrospinal fluid, an important opening to characterizing pathological phenomena associated with hypoxic-ischemic brain injury.

Biomarkers of brain damage and inflammation in patients with acute cerebral ischemia

To study the pathogenetic and clinical significance of factors of hypoxic brain damage and inflammatory mediators in the development of stroke, to improve the diagnosis using laboratory markers of brain damage and inflammation in patients with acute cerebrovascular accident. We examined 55 people with stroke of the ischemic type at the age of 74 (67; 80) years, the comparison group consisted of 25 volunteers at the age of 65.0 (62.0; 66.5) years. Depending on the outcome of ischemic stroke, patients were assigned to the discharged group or to the deceased group. Blood serum and cerebrospinal fluid (CSF) S100b protein, glial fibrillar acidic protein and interleukin-6 (IL-6); blood serum neurospecific enolase, and cortisol and C-reactive protein (CRP) were determined. Clinical blood test and assessment of fibrinogen content were performed on days 1, 3 and 10 of stroke. There is an increase in the levels of markers of brain tissue damage and systemic inflammation in the blood and CSF in response to cerebral ischemia that reflects the synergy of these pathological processes in patients with stroke, their association with the severity of stroke and its outcome. The results indicate that the postischemic release of neurospecific proteins, an increase in the content of IL-6, CRP, and cortisol make it possible to additionally characterize the severity of stroke and the body's response to damage, and predict the outcome of the disease.

Development and validation of a simple correction method for the measurement of neuron-specific enolase in hemolyzed serum samples

The Neuron-specific enolase (NSE), a biomarker of neuroendocrine tumors or ischemic brain damage, has limited clinical applicability since its measurement is overestimated by hemolysis. In this study, an NSE correction method was developed for hemolyzed samples. The NSE concentration and the hemolysis index (HI) of serum were measured before and after spiking a hemolysate prepared with red blood cells from the serum-separating tube and extrapolating the NSE value corresponding to a HI of zero. To validate the approach (n = 46), NSE concentrations and HI were measured before (NSE0 and HI0) and after spiking the samples with 50 µL (HIA, NSEA) and 100 µL (HIB, NSEB) of hemolysate. A linear regression analysis was performed between (HIA, NSEA) and (HIB, NSEB). The y-intercept was taken as the corrected NSE concentration (NSEintercept) and compared with NSE0. On the same samples, the equation of Tolan et al. was applied and the corrected values of NSE (NSEcorr) were compared to NSE0. The average bias (±SD) between the NSE0 and the NSEintercept was equal to −3.2% (± 14.3) versus 34.6% (± 19.8) against the NSEcorr. Applying the allowable total error proposed by the European Federation of Laboratory Medicine, 72% of the NSE results were adequately corrected while the reference method corrected only 8.7% of the results. The individualized hemolysis correction method developed is simple, fast, requires one serum-separating tube, provides increased accuracy compared to the method described by Tolan et al. and should improve the quality of patient care.

Enhanced S100B expression in T and B lymphocytes in spontaneous preterm birth and preeclampsia.

S100B belongs to the family of danger signaling proteins. It is mainly expressed by glial-specific cells in the brain. However, S100B was also detected in other cell likewise immune cells. This molecule was suggested as biomarker for inflammation and fetal brain damage in spontaneous preterm birth (sPTB), preeclampsia (PE) and HELLP (hemolysis, elevated liver enzymes, and low platelet count). The aim of our study was to determine the concentration of S100B in maternal and cord blood (CB) plasma and placenta supernatant as well as the expression of S100B in maternal and CB CD4+ Tcells and CD19+ Bcells in sPTB and patients delivering following PE/HELLP diagnosis compared to women delivering at term (TD). The S100B expression was further related to the birth weight in our study cohort. S100B concentration was enhanced in maternal and CB plasma of sPTB and PE/HELLP patients and positively correlated with interleukin-6 (IL-6) levels. Increased S100B was also confirmed in CB of small-for-gestational-age (SGA) infants. S100B expression in maternal blood was elevated in CD4+ Tcells of PE/HELLP patients and patients who gave birth to SGA newborns as well as in CD19+ Bcells of sPTB and PE/HELLP patients and patients with SGA babies. In CB, the expression of S100B was increased in CD19+ Bcells of sPTB, PE/HELLP and SGA babies. Our results support the hypothesis that S100B expression is enhanced in inflammatory events associated with preterm birth and that S100B expression in immune cells is a relevant marker for inflammation during pregnancy complications.

Concomitant functional impairment and reorganization in the linkage between the cerebellum and default mode network in patients with type 2 diabetes mellitus.

Increasing evidence shows that the default mode network (DMN) and cerebellum are prone to structural and functional abnormalities in patients with type 2 diabetes mellitus (T2DM). However, the type of change in the functional connection between the DMN and cerebellum is still unknown. In this study, seed-based functional connectivity (FC) analysis was used to examine the intrinsic FC of the cerebellum-DMN between healthy controls (HCs) and T2DM patients. Pearson correlation analysis was used to explore the relationship between clinical variables and changes in FC. Compared with HCs, T2DM patients showed significantly increased FC of the left crus I-left medial superior frontal gyrus, left crus I-right medial superior frontal gyrus, and right crus I-left medial orbitofrontal cortex. Compared with HCs, T2DM patients showed decreased FC of the lobule IX-the right angular gyrus. Moreover, diabetes duration was positively correlated with increased FC of the left crus I-right medial superior frontal gyrus (r=0.438, P=0.007). Concomitant functional impairment and reorganization in the linkage between the cerebellum and DMN in patients with T2DM may be a biomarker of early brain damage that can help us better understand the pathogenesis of cognitive impairment in T2DM.

Tandem Mass Tag-Based Quantitative Proteomic Analysis Reveals Pathways Involved in Brain Injury Induced by Chest Exposure to Shock Waves.

Recurrent chest blast exposure can lead to brain inflammation, oxidative stress, and mental disorders in soldiers. However, the mechanism that underlies brain injury caused indirectly by chest blasts remains unclear. It is urgent to find additional reliable biomarkers to reveal the intimate details of the pathogenesis of this phenomenon. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in rat brain at different time points after a chest blast. Data are available via ProteomeXchange with the identifier PXD025204. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Cytoscape analyses were used to analyze the proteomic profiles of blast-exposed rats. In addition, we performed Western blotting to verify protein levels. We identified 6,931 proteins, of which 255 were differentially expressed and 43, 84, 52, 97, and 49 were identified in brain tissues at 12, 24, 48, and 72 h and 1 week after chest blast exposure, respectively. In this study, the GO, KEGG, Clusters of Orthologous Groups of proteins, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses indicated that brain damage caused by chest blast exposure involved many important biological processes and signaling pathways, such as inflammation, cell adhesion, phagocytosis, neuronal and synaptic damage, oxidative stress, and apoptosis. Furthermore, Western blotting confirmed that these differentially expressed proteins and affected signaling pathways were associated with brain damage caused by chest blast exposure. This study identifies potential protein biomarkers of brain damage caused indirectly by chest blast and new targets for the treatment of this condition.

A Narrative Review of Circular RNAs in Brain Development and Diseases of Preterm Infants.

Circular RNAs (circRNAs) generated by back-splicing are the vital class of non-coding RNAs (ncRNAs). Circular RNAs are highly abundant and stable in eukaryotes, and many of them are evolutionarily conserved. They are blessed with higher expression in mammalian brains and could take part in the regulation of physiological and pathophysiological processes. In addition, premature birth is important in neurodevelopmental diseases. Brain damage in preterm infants may represent the main cause of long-term neurodevelopmental disorders in surviving babies. Until recently, more and more researches have been evidenced that circRNAs are involved in the pathogenesis of encephalopathy of premature. We aim at explaining neuroinflammation promoting the brain damage. In this review, we summarize the current findings of circRNAs properties, expression, and functions, as well as their significances in the neurodevelopmental impairments, white matter damage (WMD) and hypoxic-ischemic encephalopathy (HIE). So we think that circRNAs have a direct impact on neurodevelopment and brain injury, and will be a powerful tool in the repair of the injured immature brain. Even though their exact roles and mechanisms of gene regulation remain elusive, circRNAs have potential applications as diagnostic biomarkers for brain damage and the target for neuroprotective intervention.