Neuron-specific Enolase Research Articles

Risk Prediction Models for Invasive Mechanical Ventilation in Patients with Autoimmune Encephalitis: A Retrospective Cohort Study

Background and Objectives. Timely identification of developing severe respiratory failure in patients with autoimmune encephalitis (AE) is crucial to ensure prompt treatment with invasive mechanical ventilation (IMV), which can potentially improve the outcome. We aimed to develop a nomogram for requiring IMV based on easily available clinical characteristics. Methods. A multivariate predictive nomogram model was developed using the risk factors identified by LASSO regression and assessed by receiver operator characteristics (ROC) curve, calibration curve, and decision curve analysis. Results. The risk factors predictive of severe respiratory failure were male gender, impaired hepatic function, elevated intracranial pressure, and higher neuron-specific enolase. The final nomogram achieved an AUC of 0.770. After validation by bootstrapping, a concordance index of 0.748 was achieved. Conclusions. Our nomogram accurately predicted the risk of developing respiratory failure needing IMV in AE patients and provide clinicians with a simple and effective tool to guide treatment interventions in the AE patients.

Role of Neuron-Specific Enolase, D-Dimer and C-Reactive Protein in the Cranial Nerve Injury After Surgery of Posterior Fossa Tumor

Cranial nerve injury after posterior cranial fossa tumor surgery (PCFTS) is a common symptom in clinic. Intracranial pressure (ICP) monitoring has been widely used in patients with severe posterior cranial fossa injuries. By establishing a rat model of PCFT, we explore the correlation between neuron-specific enolase (NSE), D-Dimer (D-D) and C-reactive protein (CRP) and provide the better clinical reference to cranial fossa injury treatment. 30 SD female rats aged 20–22 months; randomly divided them into control groups and experimental groups and experimental rats were further divided into 12 for moderately increased group (21–40 mmHg) and 8 for severely increased group (>40 mmHg) to measure NSE, D-D, and CRP and analyze their relationship. NSE, DD, and CRP in severely increased group and moderately increased group were significantly higher than those in control group. NSE (103.69±7.84) μg/L, DD (1.52±0.25) mg/L, CRP (47.63)±8.59) mg/L in severely increased group was significantly higher than moderately increased group (NSE (61.77±30.11) μg/L, DD (0.97± 0.37) mg/L, CRP (30.65± 9.56) mg/L) (P < 0.05). ICP is positively correlated with NSE, DD and CRP (r = 0.775, P = 0.000, intracranial pressure=18.589+0.254NSE; r =0.872, P =0.000, IC=10.564+0.254 DD; r =0.825, P =0.000, ICP = 9.73+0.774CRP). There is a positive correlation between cranial nerve injury and NSE, D-dimer and CRP after PCFTS. It can be evaluated by detecting the above values to assess the degree of cranial nerve injury so as to predict the patient’s condition.

Potential predictive biomarker for diabetic peripheral neuropathy: serum neuron-specific enolase

Abstract The early stages of diabetic peripheral neuropathy (DPN) are symptomless. A reliable dependable and sensitive biomarker is needed for the purpose of early identification of diabetic peripheral neuropathy. The main objective of the study was to evaluate the accuracy of serum neuron-specific enolase (NSE) as a biomarker for early identification of diabetic peripheral neuropathy. Patient samples were collected from the National Diabetes Center, Mustansiriyah University; a case control study was done from April 2022 to November 2022, in Baghdad, Iraq. One hundred sixty individuals between 30 to 60 years-old were included. Participants were divided into three groups: group one included 40 type 2 diabetic patients with peripheral neuropathy, group two consisted of 40 type 2 diabetic patients without peripheral neuropathy and group three included 80 apparently in good health as the control. Toronto Clinical Neuropathy Scoring System (TCSS) was used for clinical evaluation of peripheral neuropathy. Glycated hemoglobin (HbA1c) was measured by the CLOVER A1c system. In addition, serum NSE levels were measured by Enzyme Linked Immunosorbent Assay (ELISA) technique. Age, sex, and other standard variables were used as a basis for comparisons between groups. Statistically, diabetic patients with peripheral neuropathy demonstrated higher level of NSE (28.42±6.93 ng/ml) than did either diabetic patients without peripheral neuropathy (21.07±2.0 ng/ml) or controls (12.54±2.34 ng/ml) with a high degree of significance (p <0.001). In the context of Discrimination between DPN patients and diabetic patients without neuropathy, the area under curve for neuron-specific enolase was 0.812, 95% confidence interval [CI] = 0.716-0.909, p <0.001. Cut-off value of serum neuron-specific enolase was 22.53 ng/ml, sensitivity and specificity were 70% and 77%, respectively. In the context of discrimination between DPN and controls, the area under curve for neuron-specific enolase was 1.00, 95% confidence interval was 1.0-1.0, p <0.001. At a cut-off value of serum neuron-specific enolase = 18.3 ng/ml, both the sensitivity and specificity were 100%. Neuron-specific enolase could potentially be used as a biomarker to detect early diabetic peripheral neuropathy and prevent it from developing to an advanced state.

Association of serum tumor markers with serous effusion in systemic lupus erythematosus

The objective of this study was to investigate the relationship between serum tumor markers and serous effusion in systemic lupus erythematosus (SLE) patients, thereby contributing preliminary data on the utility of these tumor markers in diagnosing serous effusion. In this retrospective analysis, clinical data of SLE patients were extracted from electronic medical records. This included the levels of serum tumor markers, including pro-gastrin-releasing peptide, neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1), various carbohydrate antigens (CA 153, CA 125, CA 19-9), along with carcinoembryonic antigen, and alpha-fetoprotein. Positivity of tumor markers was established based on serum levels surpassing the upper threshold of the respective reference ranges. This study included 149 eligible patients with SLE, of whom 38 (25.50%) had serous effusion, and the prevalence of pleural, pericardial, and peritoneal effusions was 11.41%, 14.77%, and 6.71%, respectively. The analysis revealed that patients with serous effusion had higher scores on the SLE Disease Activity Index 2000 (SLEDAI 2000) than those without serous effusion. Notably, this disparity remained significant when the serositis score was excluded from the SLEDAI 2000 calculation. The positivity rate and serum levels of CA 125 were higher in patients with serous effusion and pleural effusion. Patients with pericardial effusion demonstrated an elevated CYFRA 21-1 positivity rate and serum CA 125 and CYFRA 21-1 levels compared to patients without pericardial effusion. CA 125 and NSE were higher both in terms of positivity rate and serum levels for patients with peritoneal effusion. Through receiver operating characteristic curve analysis, a moderate relationship was discerned between the conjoined levels of CYFRA 21-1 and CA 125 and the occurrence of pericardial effusion. Additionally, CA 125, NSE, and their combination revealed the moderate diagnostic ability of peritoneal effusion. In summary, this study observed elevated serum levels of various tumor markers in SLE patients exhibiting serous effusion, which is likely attributable to lupus-induced inflammation. These findings suggest that serum tumor markers can be valuable in diagnosing pericardial and peritoneal effusions.

Fluid Biomarkers of Neurodegeneration in Mild Cognitive Impairment: A Meta‐Analysis

AbstractBackgroundMild cognitive impairment (MCI) is a well‐established prodromal stage of Alzheimer’s disease and is often accompanied by early signs of neurodegeneration (e.g., neuronal loss) that may influence subsequent prognosis. To facilitate a better characterization of the underlying neuropathology, a thorough investigation of proteins associated with neurodegenerative processes in MCI is needed. Thus, the present study systematically assessed the available literature to quantitatively evaluate cerebrospinal fluid (CSF) and peripheral blood concentrations of biomarkers related to neurodegeneration in individuals with MCI compared to healthy controls (HCs).MethodOriginal peer‐reviewed articles that assessed the following CSF and/or peripheral biomarkers: neurofilament light chain (NFL), total‐tau (T‐tau), glial fibrillary acidic protein (GFAP), heart‐type fatty acid binding protein (HFABP), neuron‐specific enolase (NSE), and S100 calcium‐binding protein B (S100B) in both MCI and HCs were included for meta‐analysis. Standardized mean differences (SMDs) and 95% confidence intervals were calculated using a random‐effects model. Heterogeneity was assessed using the I2 statistic.ResultA total of 109 study cohorts were included in the meta‐analysis. In CSF, concentrations of NFL (MCI n = 2771, HC n = 4263, SMD [95% CI] = 0.69 [0.56, 0.83], p < 0.001), GFAP (MCI n = 513, HC n = 1620, SMD [95% CI] = 0.41 [0.08, 0.74], p = 0.02), and HFABP (MCI n = 363, HC n = 245, SMD [95% CI] = 0.57 [0.23, 0.55], p < 0.001) were elevated in MCI. In peripheral blood, concentrations of NFL (MCI n = 6520, HC n = 9439, SMD [95% CI] = 0.41 [0.32, 0.49], p < 0.001), T‐tau (MCI n = 4463, HC n = 5921, SMD [95% CI] = 0.19 [0.09, 0.29], p < 0.001), and GFAP (MCI n = 1758, HC n = 3179, SMD [95% CI] = 0.39 [0.23, 0.55], p < 0.001) were increased in MCI. Significant heterogeneity was identified for all comparisons and was explored through meta regression and subgroup analysis.ConclusionThe present study identified several fluid biomarkers of neurodegeneration in MCI. Importantly, elevated biomarker levels can be detected in both CSF and less‐invasively through peripheral blood. Future studies should focus on assessing the clinical utility of monitoring these biomarkers as they may provide further insight into neuronal and astroglial pathology occurring in the early stages of cognitive decline.

Brain metabolism during delirium

AbstractBackgroundAltered cerebral glucose metabolism manifested by increased cerebrospinal fluid (CSF) lactate and decreased neuron specific enolase during delirium has been found in CSF analyses in multiple settings, although without change in CSF or blood glucose. These changes correlate with markers of delirium severity and outcomes of delirium.However, patients with delirium are acutely unwell in hospital and have multiple comorbidities. The contribution of acute illness and dementia have not been excluded.MethodWe studied two groups of acutely unwell older people in hospital after excluding underlying dementia by history and the Informant Questionnaire on Cognitive Decline in the Elderly. The first group had delirium and the second group had no delirium. All patients underwent a 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scan in hospital while unwell, and during delirium for the first group. Confounders on FDG‐PET such as structural brain lesions and medications that affect brain metabolism were excluded.Then we also compared the delirium FDG‐PET scans to a group with Alzheimer’s dementia.ResultPatients with delirium demonstrated a unique, novel pattern of brain hypometabolism that reflected symptoms of delirium. The affected areas included: bilateral thalami; right posterior cingulate cortex (PCC); right superior frontal, right infero‐lateral anterior temporal and left superior parietal cortices. The areas highly negatively correlated with delirium severity scores (Spearman’s rank correlation coefficients between ρ = ‐0.39 and ‐0.71; p values from 0.089 to 0.001) and performance on a range of relevant neuropsychological tests, for example thalami and Trail Making Test B (Spearman’s ρ = ‐0.52; p = 0.028). Direct comparison to AD scans significant thalamic hypometabolism (p<0.01) in delirium, but the PCC was not different.ConclusionIn patients with acute illness but without dementia, delirium is accompanied by regional cerebral hypometabolism in a distribution that is not consistent with any known pattern of dementia. While there is some overlap with AD, thalamic hypometabolism is atypical of AD and consistent with the clinical features of delirium.ReferencesNitchingham AR, Pereira JV‐B, Wegner EA, Oxenham V, Close J Caplan GA. Regional cerebral hypometabolism on 18F‐FDG PET/CT scan in delirium is independent of acute illness and dementia. Alzheimers & Dementia 2022; 1‐10.

Curcumin alleviates traumatic brain injury induced by gas explosion through modulating gut microbiota and suppressing the LPS/TLR4/MyD88/NF-κB pathway.

Gas explosions (GE) are a prevalent and widespread cause of traumatic brain injury (TBI) in coal miners. However, the impact and mechanism of curcumin on GE-induced TBI in rats remain unclear. In this study, we simulated GE-induced TBI in rats and administered curcumin orally at a dose of 100mg/kg every other day for 7days to modulate the gut microbiota in TBI rats. We employed 16S rRNA sequencing and LC-MS/MS metabolomic analysis to investigate changes in the intestinal flora and its metabolic profile. Additionally, we utilized ELISA, protein assays, and immunohistochemistry to assess neuroinflammatory signaling molecules for validation. In a rat TBI model, GE resulted in weight loss, pathological abnormalities, and cortical hemorrhage. Treatment with curcumin significantly mitigated histological abnormalities and microscopic mitochondrial structural changes in brain tissue. Furthermore, curcumin treatment markedly ameliorated GE-induced brain dysfunction by reducing the levels of several neuroinflammatory signaling molecules, including neuron-specific enolase, interleukin (IL)-1β, IL-6, and cryptothermic protein 3. Notably, curcumin reshaped the gut microbiome by enhancing evenness, richness, and composition. Prevotella_9, Alloprevotella, Bacilli, Lactobacillales, Proteobacteria, and Gammaproteobacteria were identified as prominent members of the gut microbiota, increasing the linear discriminant analysis scores and specifically enhancing the abundance of bacteria involved in the nuclear factor (NF)-κB signaling pathway, such as Lachnospiraceae and Roseburia. Additionally, there were substantial alterations in serum metabolites associated with metabolic NF-κB signaling pathways in the model group. Curcumin administration reduced serum lipopolysaccharide levels and downregulated downstream Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling. Furthermore, curcumin alleviated GE-induced TBI in rats by modulating the gut microbiota and its metabolites. Based on these protective effects, curcumin may exert its influence on the gut microbiota and the TLR4/MyD88/NF-κB signaling pathways to ameliorate GE-induced TBI.

Retracted: Related Factors and a Threshold of the Maximum Neuron-Specific Enolase Value Affecting the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage

Retracted: Related Factors and a Threshold of the Maximum Neuron-Specific Enolase Value Affecting the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage

β-asarone improves cognitive impairment and alleviates autophagy in mice with vascular dementia via the cAMP/PKA/CREB pathway

BackgroundVascular dementia (VD) is the second most common type of dementia after Alzheimer's disease. β-asarone, a major component of Acorus tatarinowii Schott, is important in neurodegenerative and neurovascular diseases. Studies have confirmed that β-asarone can mitigate autophagy and reduce damage in hypoxic cells. We also reported that β-asarone improves learning and memory. This study further clarifies whether β-asarone attenuates cerebral ischaemic injury by acting through the cAMP/PKA/CREB pathway in VD model mice. MethodsHere, genes and potential pathways that may be targeted by β-asarone for the treatment of transient cerebral ischaemia (TCI) and cognitive impairment (CI) were obtained using network pharmacology. The two-vessel occlusion method was used to establish the VD model. The Morris water maze test was used to evaluate the effects on memory. Then, the protein levels of mitofusin-2 (Mfn2), brain-derived neurotrophic factor (BDNF), optic atrophy 1 (OPA1), cyclic adenosine monophosphate (cAMP), myelin basic protein (MBP), matrix metalloproteinase-9 (MMP9) and neuron specific enolase (NSE) were determined by ELISA. The levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were measured using commercial kits. Then, qRT-PCR was employed to investigate the expression of the candidate genes screened from the protein-protein interaction (PPI) network. Furthermore, the expression of the autophagy-related proteins Beclin-1, (microtubule-associated protein light chain 3) LC3, p62, postsynaptic density protein 95 (PSD95), protein kinase A (PKA), pPKA, cyclic-AMP response binding protein (CREB), and pCREB was determined by western blotting. The expression of autophagy-related proteins, PSD95 and translocase of outer mitochondrial membrane 20 (TOM20) was determined by immunofluorescence analyses. ResultsThe network pharmacological analysis showed 234 targets related to β-asarone, 1,118 genes related to TCI and 2,039 genes associated with CI. Our results confirm that β-asarone treatment not only alleviated brain damage in the VD model by improving mitochondrial and synaptic function, reducing neuronal injury and upregulating the expression of antioxidants but also effectively improved the cognitive behaviour of VD model mice. Moreover, β-asarone downregulated VD-induced RELA and CCND1 mRNA expression. In addition, we validated that β-asarone increased the phosphorylation of PKA and CREB and upregulated cAMP protein expression. The results showed that the cAMP/PKA/CREB signalling pathway was upregulated. Moreover, β-asarone administration decreased the protein expression levels of Beclin-1 and LC3 and increased the expression levels of p62 in VD model mice. Conclusionsβ-asarone inhibits Beclin-1-dependent autophagy and upregulates the cAMP/PKA/CREB signalling pathway to attenuate mitochondrial and synaptic damage from cerebral ischaemia and improve learning and cognitive abilities in VD model mice.

Self-supported PtPdMnCoFe high-entropy alloy with nanochain-like internetworks for ultrasensitive electrochemical immunoassay of biomarker

High-entropy nanomaterials are regarded as the new research hotspots for their intriguing “cocktail effect”. Herein, self-supported PtPdMnCoFe high-entropy alloy with nanochain-like internetworks (PtPdMnCoFe HEAINN) were synthesized by a one-pot co-reduction method, where newly-generated H2 bubbles served as dynamic template, as identified by a series of characterizations. The high-entropy architecture was certificated effectiveness for reduction of H2O2, which was explored as signal amplifier to develop a novel label-free electrochemical amperometric immunosensor for ultrasensitive determination of biomarker neuron-specific enolase (NSE). In the optimized analytical surroundings, the as-fabricated sensor showed a broad linear range of 0.1 pg mL–1 to 200 ng mL–1 for immunoassay of NSE with a low limit of detection (LOD = 0.0036 pg mL–1, S/N = 3), coupled by its quantification in human serum samples with satisfactory results. This work provides valuable guidance for potential applications of high-entropy alloyed materials in biosensors and immunoanalysis.

Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageⅠA lung cancer

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.

Evaluation of Cognitive and Biochemical Brain Status in Patients after Carotid Endarterectomy

INTRODUCTION: In the large studies such as NASCET, ESCT, VACS, ACAS and ACST-1, the role of alteration of the cognitive functions of a patient in the early and long-term postoperative periods have not been determined.
 AIM: To evaluate the biochemical parameters of cerebral functions, the cognitive status of patients, and their interrelation after carotid endarterectomy.
 MATERIALS AND METHODS: The study involved 60 patients divided into two groups. The mean age was 67.3 ± 7.9 years, there were 49 (81%) men and 19 (19%) women. Group A included ‘symptomatic’ patients (n = 30) who underwent carotid endarterectomy and had a history of an acute cerebrovascular event. Group B included ‘asymptomatic’ patients (n = 30) who underwent carotid endarterectomy but had no history of cerebrovascular events. As part of the study, the following data were evaluated within a 6-month period: cognitive status (on MMSE, FAB, MoCA-test, NIHSS scales), biochemical parameters (S100b protein, neuron specific enolase (NSE), brain derived neurotrophic growth factor (BDNF)) and the ultrasound data of the carotid arteries.
 RESULTS: Patients of group A showed improvement of the cognitive status by the 6th month on MMSE scale (p = 0.001) and in MoCA-test (p = 0.09) relative to the initial parameters; on FAB scale relative to the data after 1 month (p = 0.01); a decline of the level of neurological deficit on NIHSS scale (p = 0.01). In group A, an inverse correlation was found between the results on MMSE scale and resistance index (r = -0.675; p = 0.005), and a direct correlation between the results on FAB scale and the end diastolic pressure in the internal carotid artery (r = +0.912; p = 0.005) according to the ultrasound data. The data obtained in group B, reflected improvement of the cognitive status by the 6th month only by 2 points on MoCA test (p = 0. 03) relative to the initial data. Besides, in 6 months after the surgery, there was a 2-fold increase in S100b marker (p = 0.01) and NSE protein (p = 0.02) and a 1.5-fold increase in BDNF protein as compared to the initial values (p = 0.005).
 CONCLUSIONS: Carotid endarterectomy leads to improvement of the cognitive status evaluated on MMSE, FAB, MoCA, NIHSS scales in the long-term postoperative period in symptomatic patients. The extent of improvement of neuropsychological status depends on the level of the end diastolic pressure and resistance index in the internal carotid artery on the operated side.

COMPARISON BETWEEN ACTIVE ABDOMINAL COMPRESSION-DECOMPRESSION CARDIOPULMONARY RESUSCITATION AND STANDARD CARDIOPULMONARY RESUSCITATION IN ASPHYCTIC CARDIAC ARREST RATS WITH MULTIPLE RIB FRACTURES.

Background: Active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR) is potentially more effective for cardiac arrest (CA) with multiple rib fractures. However, its effect on survival rates and neurological outcomes remains unknown. This study aimed to assess if AACD-CPR improves survival rates and neurological outcomes in a rat model of asphyctic CA with multiple rib fractures. Methods: Adult male Sprague-Dawley rats were randomized into three groups-AACD group (n = 15), standard cardiopulmonary resuscitation (STD-CPR) group (n = 15), and sham group (n = 10)-after bilateral rib fractures were surgically created and endotracheal intubation was performed. AACD-CPR and STD-CPR groups underwent 8 min of asphyxia followed by different CPR techniques. The sham group had venous catheterization only. Physiological variables and arterial blood gases were recorded at baseline and during a 4-h monitoring period. Neurological deficit scores (NDSs) and cumulative survival rates were assessed at 24, 48, and 72 h. NDS, serum biomarkers, and hippocampal neuron analysis were used to evaluate neurological outcomes. Results: No statistical differences were observed in the return of spontaneous circulation (ROSC), 24-, 48-, and 72-h survival rates between the AACD-CPR and STD-CPR groups. AACD-CPR rats had lower serum levels of neuron-specific enolase and S100B at 72 h post-ROSC, and higher NDS at 72 h post-ROSC compared with STD-CPR animals. Cellular morphology analysis, hematoxylin and eosin staining, and TUNEL/DAPI assays showed more viable neurons and fewer apoptotic neurons in the AACD-CPR group than in the STD-CPR group. Conclusions: AACD-CPR can achieve similar survival rates and better neurological outcome after asphyxial CA in rats with multiple rib fractures when compared with STD-CPR.

Compositional changes in fecal microbiota in a new Parkinson's disease model: C57BL/6-Tg(NSE-haSyn) mice

BackgroundThe gut–brain axis (GBA) in Parkinson's disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model.ResultsThe expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSE-hαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity.ConclusionsThe motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.

Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study

Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated. Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E ≤4) was improved. First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice. European Union 7th Framework program, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, and NeuroTrauma Sciences.

The Application Value of Combined Detection of Serum IL-6, LDH, S100, NSE, and GFAP in the Early Diagnosis of Brain Damage Caused by Neonatal Asphyxia.

We aimed to investigate the correlation and clinical significance between a group of serum biomarkers and brain damage caused by neonatal asphyxia, and to provide sensitive and effective detection methods for early diagnosis and prognosis improvement. We enrolled neonates hospitalized in the neonatal department of The Affiliated Hospital of Inner Mongolia Medical University of China from June 2020 to June 2021 as the study subjects. The levels of inter-leukin-6 (IL-6), lactate dehydrogenase (LDH), S100 protein, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP) in serum samples were measured using electrochemiluminescence (ECL), enzyme-linked immunosorbent assay (ELISA) or rate method and the correlations between these serum biomarkers and the degree of neonatal asphyxia and brain damage were statistically analyzed using Spearman test. The levels of serum IL-6, LDH, S100, NSE, and GFAP in the neonatal asphyxia with brain damage group within 12 hours after birth were significantly higher than those in the neonatal asphyxia without brain damage group (all P<0.05). Additionally, these levels were positively correlated with the degree of asphyxia. The Area Under the Curve (AUC) of receiver operating characteristic (ROC) curves of IL-6 (0.8819), LDH (0.8108), S100 (0.8719), NSE (0.8719), and GFAP (0.8073) were revealed. The combined detection of serum marker levels can simultaneously reflect neuronal injury, glial cell injury, and inflammatory injury, improve the accuracy of diagnosis of neonatal asphyxia with brain damage, and enable the formulation of treatment strategies as early as possible to reduce the incidence of complications of brain damage.

Neurofilament Light Chain levels during admission after out-of-hospital cardiac arrest is associated with cognitive performance at 3-months follow-up

Abstract Background Patients who are resuscitated from out-of-hospital cardiac arrest (OHCA) and hospitalized in coma are at high risk of mortality or brain injury with consequent cognitive impairment, and new therapy are wanted. Biomarkers of brain injury, including Neuron-specific enolase (NSE) and Neurofilament light chain (NfL), predict mortality from cerebral injury. However, prognostication of cognitive dysfunction after discharge in OHCA survivors is challenging. Montreal Cognitive Assessment (MoCA) is a recommended standardized cognitive function testing which is used in the months following OHCA. Nevertheless, prognostic methods assessed in the initial phase of admittance which identify patients at risk of developing cognitive impairment are needed. Purpose To investigate the effect of tocilizumab administered at admission after OHCA on cognitive performance assessed by MoCA at 3-month follow-up, and to investigate the association to time-to-ROSC, and NSE as well as NfL levels during index admission with MoCA at follow-up. Methods The IMICA trial evaluated tocilizumab for reducing systemic inflammation after OHCA and randomized 80 comatose adult patients at admission to an infusion of either tocilizumab (8mg/kg, maximum 800mg) or placebo. NSE at 48 hours was measured as part of routine biochemistry based on serum samples, and NFL at 48 hours was measured in serum samples from the biobank. Time-to-ROSC was reported from pre-hospital data and cognitive performance at 3 months follow-up were assessed by the MoCA test. The association between MoCA and time-to-ROSC, NSE and NfL was assessed by Spearman’s correlation analyses. Results At follow-up, 35 patients had a MoCA test performed, while 28 patients were deceased, and 17 were alive without having an available MoCA score. There was no difference in MoCA scores at follow-up in the tocilizumab group compared to placebo group (p=0.72), and therefore results for both groups were pooled for analyses. NfL was found to be inversely correlated with MoCA score, r = -0.49, p = 0.003 (Figure), while there were no correlations with MoCA for time-to-ROSC or NSE (p = 0.46 and p = 0.34). Conclusions NfL measured at 48 hours after admission was inversely correlated with cognitive performance at 3 months for survivors of OHCA.

A study on placental expression of neuronal markers in intrauterine growth restriction

Introduction and Aim: The restriction of intrauterine growth (IUGR) has a 20% recurrence rate and is one of the leading causes of postnatal illness and death. The diagnosis of intrauterine retardation refers to the infant's increased risk of neurological issues over an extended period, neonatal morbidity, and mortality, and in utero death. Materials and Methods: One hundred placenta samples were collected and divided into cases and controls. Clearance from the ethics committee was taken from the institute prior to the commencement of this study. Exclusion criteria include the patients with multiple pregnancies, unknown gestational age, gestational diabetes, and HIV. The inclusion criteria are the singleton pregnancy, normal and cesarean section, maternal age between 18-35 years and GA between 34 – 41 weeks. Standard immunohistochemistry protocols were followed for the study and glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) markers were used as neuronal markers. Results: Strong immunoreactivity of glial fibrillary acidic protein and neuron specific enolase was observed in fetal growth restriction placenta indicating perinatal brain damage of neonate. Conclusion: In our study we observed strong positive immunoreactivity of GFAP and NSE in IUGR only. This study suggests that these markers are used to predict brain damage in IUGR neonates.

Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial

PurposePatients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and brain injury are components of the post-cardiac arrest syndrome, and can be assessed by systemic interleukin 6 (IL-6) and neuron-specific enolase (NSE). Anti-inflammatory treatment with methylprednisolone may dampen inflammation, thereby improving outcome. This study aimed to determine if prehospital high-dose methylprednisolone could reduce IL-6 and NSE in comatose OHCA patients.MethodsThe STEROHCA trial was a randomized, blinded, placebo-controlled, phase II prehospital trial performed at two cardiac arrest centers in Denmark. Resuscitated comatose patients with suspected cardiac etiology were randomly assigned 1:1 to a single intravenous injection of 250 mg methylprednisolone or placebo. The co-primary outcome was reduction of IL-6 and NSE-blood levels measured daily for 72 h from admission. The main secondary outcome was survival at 180 days follow-up.ResultsWe randomized 137 patients to methylprednisolone (n = 68) or placebo (n = 69). We found reduced IL-6 levels (p < 0.0001) in the intervention group, with median (interquartile range, IQR) levels at 24 h of 2.1 pg/ml (1.0; 7.1) and 30.7 pg/ml (14.2; 59) in the placebo group. We observed no difference between groups in NSE levels (p = 0.22), with levels at 48 h of 18.8 ug/L (14.4; 24.6) and 14.8 ug/L (11.2; 19.4) in the intervention and placebo group, respectively. In the intervention group, 51 (75%) patients survived and 44 (64%) in the placebo group.ConclusionPrehospital treatment with high-dose methylprednisolone to resuscitated comatose OHCA patients, resulted in reduced IL-6 levels after 24 h, but did not reduce NSE levels.

High versus low mean arterial pressure targets after out-of-hospital cardiac arrest: a meta-analysis of randomized controlled trials

Abstract Background Out-of-hospital cardiac arrest (OHCA) is a significant healthcare burden, with an average global incidence of 55 per 100,000 person-years among adults. OHCA patients require blood pressure support to maintain effective mean arterial pressure (MAP) for cerebral reperfusion, which is usually achieved by intravascular fluids and vasopressors in the intensive care unit (ICU). Targeting a specific MAP has been evaluated as a treatment strategy after OHCA; however, the current evidence lacks clear guidelines regarding the optimal MAP target after OHCA. Purpose We aim to evaluate the efficacy of targeting a high MAP (&amp;gt;70 mmHg) versus a low MAP target (&amp;lt; 65 mmHg) after OHCA resuscitation. Methods We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through January 18th, 2023. Continuous and dichotomous outcomes were pooled using mean difference (MD) and risk ratio (RR) along with confidence interval (CI), using Revman V. 5.4 software. Our review protocol was prospectively published on PROSPERO with ID: CRD42023395333. Results Four RCTs with a total of 1070 patients (531 in the high MAP target group and 534 in the low MAP target group) were included in our analysis. High MAP target was significantly associated with decreased ICU length of stay (MD: -0.78 with a 95 CI [-1.54, -0.02], P= .04) and mechanical ventilation duration (MD: -0.91 with a 95 CI of [-1.51, -0.31], P= .003). However, There was no difference between targeting a high MAP versus low MAP regarding all-cause mortality (RR: 1.07 with a 95% CI [0.91, 1.27], P= 0.4), favorable neurological recovery (cerebral categories scale (CPC) ≤ 2) (RR: 1.02 with a 95% CI [0.93, 1.13], P= 0.68), and neuron-specific enolase (NSE) at 48 hours (MD: 0.54 with 95% CI [-1.67, 2.75], P = 0.63), the incidence of adverse events, including any bleeding (RR: 0.89 with a 95% CI [0.69, 1.36], P= 0.39); arrhythmia (RR: 0.91 with a 95% CI [0.46, 1.82], P= 0.79), or acute kidney injury (RR: 0.80 with a 95% CI [0.36, 1.76] and P = 0.58). Conclusion In patients with OHCA who have been resuscitated, targeting a higher MAP significantly reduced the ICU length of stay and mechanical ventilation, implying potential clinical benefit with an acceptable safety margin. However, there was no difference between targeting a high MAP versus a low MAP regarding all-cause mortality, favorable neurological recovery, and NSE. Therefore, further RCTs are still warranted to elucidate the potential clinical benefit of targeting a high MAP after OHCA before endorsement in clinical practice.Figure 1Figure 2