Calcium-binding Protein Levels Research Articles

Effects of Esketamine Combined with Dexmedetomidine on Early Postoperative Cognitive Function in Elderly Patients Undergoing Lumbar Spinal Surgery: A Double-Blind Randomized Controlled Clinical Trial.

Postoperative cognitive dysfunction (POCD) is a common complication after surgery in elderly patients, and its prevalence can be up to 25.6% at one week after noncardiac surgery. This study mainly evaluates the combined effects of esketamine and dexmedetomidine on the incidence of POCD in elderly patients undergoing lumbar spine surgery and explores the underlying mechanisms. A total of 162 elderly patients undergoing lumbar spine surgery were randomized into three groups: esketamine combined with dexmedetomidine group (ED group), esketamine group (E group), and dexmedetomidine group (D group). Primary outcome measures included the incidence of POCD on the first postoperative day. Secondary outcomes included the incidence of POCD on the third postoperative day, first postoperative day serum levels of neuron-specific enolase (NSE) and calcium-binding protein β (S100β), patient visual analog scale (VAS) scores at 2, 24, and 48hours postoperatively, and the incidence of adverse events. The incidence of POCD on the first postoperative day was significantly lower in the ED group compared to the E group (P = 0.017), with no significant differences when compared to the D group (P = 0.064). The levels of serum NSE in patients in the ED group on the first postoperative day were significantly lower than those in E group and D group (ED group vs E group, P = 0.028; ED group vs D group, P = 0.048). The results for the S100β were similar to those for the NSE (ED group vs E group, P = 0.005; ED group vs D group, P = 0.011). The combination of esketamine and dexmedetomidine effectively reduces the incidence of POCD on the first postoperative day in elderly patients undergoing lumbar spine surgery.

Insights for possible association and impact of thyroidectomy to osteoarthritis

Background and aim of studyThyroidectomy and osteoarthritis have drawn more attention in last decades due to increase various local and systemic risk factors. This study is aimed to determine the association and impact between thyroidectomy and osteoarthritis by serological measurement of most specific related markers.ResultsMeasurement of thyroid markers showed the level of thyroid-stimulating hormone (TSH) was significantly increased, while parathyroid hormone (PTH), triiodothyronine (T3), and thyroxine (T4) levels were decreased in osteoarthritis subjected to thyroidectomy group (OTG) when compared to hyperthyroidism subjected to thyroidectomy group (TG), osteoarthritis group (OG), and healthy control group (CG). Detection the activity of bone markers showed the level of R-factor was significantly elevated concomitant with significant reduction in Dickkopf related protein 1 (DKK1), human hyaluronan-binding protein 2 (HABP2), osteocalcin (OC) in OG and OTG groups, while osteopontin (OPN) and procollagen I C-terminal propeptide (PICP) were significantly increased and decreased in TG and OTG. Furthermore, the level of S100 Calcium binding protein (S100CBP) showed significant decreased in patient’s groups, while TG with OTG groups exhibited significant reduction in sclerostin (SOST) concentration. Regarding the inflammatory markers, the levels of interleukin-1 (IL-1) was increased in the OTG, while the level of interleukin-10 (IL-10) was increased in OG and TG groups, and reduced in OTG. While, the level of transforming growth factor-beta (TGF-β) was decreased in OG and TG associated with significant increases in tumor necrosis factor-alpha level (TNF-α) in OTG. Measurement of oxidant and antioxidant activity markers showed the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were significantly reduced in all patient’s groups compared to control, except the level of CAT in TG, whereas, malondialdehyde (MDA) level was increased in OG and OTG patients. Furthermore, the levels of Alkaline phosphatase (ALP), C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were increased in all patient groups compared to control, while fatty acid-binding protein (FABP) level was increased in OTG only.ConclusionThis unique study in Iraq is identified the interaction effect and impact of thyroidectomy to osteoarthritis according to the results that showed various changes and degree of correlation of study biomarkers in all patient groups, however more depth of specific quantitative and qualitative studies are required to support this association and the impact claim at molecular level.

Biochemical markers of neuro-myocardial damage after pulmonary vein isolation: the effect of different energy sources

Abstract Background Pulmonary vein isolation (PVI) by thermal energy, both radiofrequency (RF) and cryoenergy(Cryo), is associated with a significant release of myocardial and collateral neural injury markers. Damage to periatrial ganglionated plexi also results in a substantial change in cardiac autonomic regulations. On the contrary, pulsed electric field (PEF) energy tends to spare cardiac neural tissue. Purpose To quantify the impact of different ablation energy sources that are used for PVI on neuro-myocardial damage by the assessment of specific biomarkers. Methods A study enrolled 85 patients with paroxysmal atrial fibrillation who underwent PVI (age: 61 ± 12 years, 74% males). In 23 patients, RF energy was delivered by the irrigated-tip catheter, while 30 patients were ablated using a second-generation cryoballoon catheter. In 32 patients, PVI was performed using a multipolar pentaspline catheter and PEF energy. Peripheral venous blood samples for assessing the plasmatic levels of S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), high-sensitivity troponin I and T (hsTnI and hsTnT) were obtained before, immediately after the PVI, and the next day (usually 18-24 hours after the procedure). Study groups were compared regarding absolute biomarker levels and hsTnT/S100B ratio (a surrogate of cardioselectivity). Results Following successful PVI, a significant increase in plasma levels of all biomarkers was observed: DhsTnT = 1040±434 ng/L, 1731±830 ng/L and 1010±397 ng/L; DhsTnI = 1504±918 ng/L, 16464±11911 ng/L and 10789±7589 ng/L; DS100B: 0.04±0.02 mg/L, 0.03±0.04 mg/L and 0.14±0.08 mg/L; DNSE: 34±72 ng/mL, 27±53 ng/mL and 45±52 ng/mL (all with P <0.001) for RF, PEF and Cryo groups, respectively. A direct comparison of maximal biomarker levels between study groups is depicted in the Figure. The hsTnT/S100B ratio was 23±14, 12±6, and 6±3 in PEF, RF, and Cryo groups, respectively (ANOVA P <0.01), indicating that PEF was 1.9-times and 3.8-times more cardioselective than RF and Cryo, respectively. Following the PVI, the heart rate accelerated by 2±8, 13±14, and 9±11 bpm in the PEF, RF, and Cryo groups, respectively. No correlation was observed between S100B release and HR acceleration (R = 0.07, P = 0.55). Conclusion Compared to thermal energy sources, PEF energy induces more specific damage to cardiomyocytes than cardiac nerves. There was no correlation between S100B release and HR acceleration.

The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling.

Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR. We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting. Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR. Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.

Increased Serum S100β Concentration is Associated with Depression in Parkinson's Disease.

To explore the relationship between the serum level of S100 calcium-binding protein, beta chain (S100β) and Parkinson's disease (PD) with depression. A total of 145 patients with PD and 60 healthy controls matched for sex, age, and years of education in our hospital were selected. Fluorescence quantitative immunochromatography was used to quantify the level of S100β in serum. Clinical manifestations were assessed by Unified Parkinson's Disease Rating Scale part-III (UPDRS-III), Hoehn & Yahr (H-Y) stage and 17-item Hamilton Rating Scale for Depression (HAMD-17). According to the results of HAMD-17, PD patients were divided into PD with depression group and PD without depression group. The relationship between serum S100β and HAMD-17 scores in PD patients with depression was investigated through correlation analysis and multivariate regression analysis, and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum S100β. The level of serum S100β in PD with depression group was significantly higher than that in PD without depression group and control group. In PD patients with depression, serum S100β level was positively correlated with UPDRS-III score, H-Y Scale and HAMD-17 score. The HAMD-17 score was positively correlated with the UPDRS-III and H-Y scales, and the increase in the HAMD-17 score was associated with women. Elevated serum S100β level and UPDRS-III score are independent risk factors for PD with depression. Analysis of receiver operating characteristic (ROC) curves showed that the serum S100β level with a cutoff of 0.28 ng/mL distinguished patients with PD with or without depression with an area under the ROC curve (AUC) of 0.742, sensitivity of 0.696, and specificity of 0.779. The serum S100β level could be a biomarker of PD with depression.

FGF21 modulates hippocampal cold-shock proteins and CA2-subregion proteins in neonatal mice with hypoxia-ischemia.

Fibroblast growth factor 21 (FGF21) is a neuroprotectant with cognitive enhancing effects but with poorly characterized mechanism(s) of action, particularly in females. Prior studies suggest that FGF21 may regulate cold-shock proteins (CSPs) and CA2-marker proteins in the hippocampus but empirical evidence is lacking. We assessed in normothermic postnatal day (PND) 10 female mice, if hypoxic-ischemic (HI) brain injury (25 min 8% O2/92% N2) altered endogenous levels of FGF21 in serum or in the hippocampus, or its receptor β-klotho. We also tested if systemic administration of FGF21 (1.5 mg/kg) modulated hippocampal CSPs or CA2 proteins. Finally, we measured if FGF21 therapy altered markers of acute hippocampal injury. HI increased endogenous serum FGF21 (24 h), hippocampal tissue FGF21 (4d), and decreased hippocampal β-klotho levels (4d). Exogenous FGF21 therapy modulated hippocampal CSP levels, and dynamically altered hippocampal CA2 marker expression (24 h and 4d). Finally, FGF21 ameliorated neuronal damage markers at 24 h but did not affect GFAP (astrogliosis) or Iba1 (microgliosis) levels at 4d. FGF21 therapy modulates CSP and CA2 protein levels in the injured hippocampus. These proteins serve different biological functions, but our findings suggest that FGF21 administration modulates them in a homeostatic manner after HI. Hypoxic-ischemic (HI) injury in female post-natal day (PND) 10 mice decreases hippocampal RNA binding motif 3 (RBM3) levels in the normothermic newborn brain. HI injury in normothermic newborn female mice alters serum and hippocampal fibroblast growth factor 21 (FGF21) levels 24 h post-injury. HI injury in normothermic newborn female mice alters hippocampal levels of N-terminal EF-hand calcium binding protein 2 (NECAB2) in a time-dependent manner. Exogenous FGF21 therapy ameliorates the HI-mediated loss of hippocampal cold-induced RNA-binding protein (CIRBP). Exogenous FGF21 therapy modulates hippocampal levels of CA2-marker proteins after HI.

S100B Protein but Not 3-Nitrotyrosine Positively Correlates with Plasma Ammonia in Patients with Inherited Hyperammonemias: A New Promising Diagnostic Tool?

Individuals with inherited hyperammonemias often present developmental and intellectual deficiencies which are likely to be exaggerated by hyperammonemia episodes in long-term outcomes. In order to find a new, systemic marker common to the course of congenital hyperammonemias, we decided to measure the plasma level of S100 calcium-binding protein B (S100B), which is associated with cerebral impairment. Further, we analyzed three mechanistically diverged but linked with oxidative-nitrosative stress biochemical parameters: 3-nitrotyrosine (3-NT), a measure of plasma proteins' nitration; advanced oxidation protein products (AOPP), a measure of protein oxidation; and glutathione peroxidase (GPx) activity, a measure of anti-oxidative enzymatic capacity. The plasma biomarkers listed above were determined for the first time in congenital hyperammonemia. Also, the level of pro- and anti-inflammatory mediators (i.e., IL-12, IL-6, IL-8, TNF-α, IL-1β, and IL-10) and chemokines (IP-10, MCP-1, MIG, and RANTES) were quantified. S100B was positively correlated with plasma ammonia level, while noticeable levels of circulating 3-NT in some of the patients' plasma did not correlate with ammonia concentration. Overall, the linear correlation between ammonia and S100B but not standard oxidative stress-related markers offers a unique perspective for the future identification and monitoring of neurological deficits risk-linked with hyperammonemia episodes in patients with inherited hyperammonemias. The S100B measure may support the development of therapeutic targets and clinical monitoring in these disorders.

Identification of pyroptosis‑related genes in neuropathic pain based on bioinformatics analysis.

Pyroptosis is defined as inflammation-induced programmed cell death. However, gene expression levels related to pyroptosis and their role in neuropathic pain (NP) remain unclear. The present study aimed to develop and validate an NP-predictive signature based on the genes associated with pyroptosis. Gene expression level profiles were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis was used to identify the pyroptotic genes most highly associated with NP. NP-related pyroptosis gene signature was constructed using multivariate logistic regression. A rat model of neuropathic pain was established through chronic constriction injury to analyse the inflammatory infiltration and myelin damage around the sciatic nerve, and examine the expression levels of macrophage markers S100 calcium-binding protein β (S100β) and ionized calcium-binding adapter molecule 1 (Iba-1). Finally, flow cytometry analysis was used to examine the lipopolysaccharide (LPS)-induced cell death ratio of RSC96 cells (Schwann cells), while the expression levels of LPS-induced pyroptosis-related genes in RSC96 cells were measured via reverse transcription-quantitative PCR. The results demonstrated that pyroptosis-related genes (gasdermin D, NLR family pyrin domain containing 3, neuronal apoptosis inhibitory protein and NLR family CARD domain containing 4) were identified to increase the risk of NP. NP-related pyroptosis signatures were constructed based on these four genes. Moreover, the high-risk group had a higher level of macrophage infiltration compared with the low-risk group, as determined by the CIBERSORT algorithm. H&E staining results showed that the myelin structure of the sciatic nerve tissue of chronic constriction injury (CCI) rats was destroyed and inflammatory cells infiltrated around neurons. The results of immunohistochemistry showed that compared with in the sham group, the expression levels of Iba-1 and sS100β in the sciatic nerve of the CCI group were increased. Furthermore, the expression levels of cell death and pyroptosis-related genes in Schwann cells induced by LPS were increased compared with in the control group. In conclusion, an NP-related pyroptosis gene signature was constructed based on four pyroptosis-related genes and it was found that the expression of pyroptosis-related genes was upregulated in the early steps of the neuroinflammatory process in RSC96 cells.

Effect of electroacupuncture at Baihui ameliorated neurologic deficit and hemodynamic stability in rat model of post-cardiac arrest syndrome

To observe the results of electroacupuncture (EA) on the resuscitation of a rat model of asphyxia cardiac arrest (CA). And to explore its effect on the neurologic deficits and hemodynamic instability of post-cardiac arrest syndrome (PCAS). A total of 107 male SD rats were randomly divided into sham, CA, and EA groups. Each group received arterial catheterization and tracheal intubation. The sham group was not induced asphyxia. Asphyxial cardiac arrest was established by endotracheal tube clamping. Rats in the CA group received basic respiratory support and fluid resuscitation in return of spontaneous circulation (ROSC) and rats in the EA group received EA at Baihui based on the treatment of CA group after ROSC, with a dense-dispersed wave at frequencies of 4-20 Hz, while the current intensity was adjusted minimum to induce a twitch of the scalp, the course of treatment was 30 minutes. The baseline data, hemodynamics after ROSC, neurological deficit score (NDS), pathological changes of brain tissue, and levels of serum biomarker were recorded and compared among the three groups. The 72-hour survival of rats was analyzed by Kaplan-Meier survival curve. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of necrotic neurons in the hippocampal CA1 region of rat brain. Meanwhile, Nissl staining and TdT-mediated dUTP nick-end labeling (TUNEL) were used to detect cell apoptosis and injury. Compared with the CA group, the mean arterial pressure (MAP) in the EA group increased significantly at 15 minutes after ROSC [mmHg (1 mmHg ≈ 0.133 kPa): 125.00 (94.00, 136.25) vs. 92.00 (72.00, 122.50), P < 0.05]. There was no significant difference in the NDS score between the EA group and the sham group. Still, the NDS score of the rats in the CA group at 6 hours after ROSC were significantly lower than that in the sham group (46.00±10.61 vs. 80.00±0.00, P < 0.05). Kaplan-Meier survival curve analysis showed that EA did not improve the 72-hour survival rate of rats (100% in the sham group, 25% in the CA group, and 30% in the EA group, P > 0.05). The analysis by TUNEL showed that the apoptosis rate of neurons in CA1 region of the hippocampus in EA group at 6 hours after ROSC was significantly lower than that in CA group [(62.84±2.67)% vs. (71.29±3.70)%, P < 0.05]. Compared with the CA group, the level of serum S100 calcium binding protein B (S100B) in the EA group at 6 hours after ROSC was significantly lower (ng/L: 19.30±13.87 vs. 132.28±31.67, P < 0.05), but there were no significant differences in the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) between these two groups. In the present study, EA at Baihui can stabilize the hemodynamic, moreover, it has a particular neuroprotective effect on PCAS rats. Still, EA at Baihui does not reduce the systemic inflammatory response and improve the survival rate of rats, and its mechanism remains to be verified in further research.

Changes of biochemical biomarkers in the serum of children with convulsion status epilepticus: a prospective study

BackgroundConvulsive status epilepticus (CSE) is a common neurologic emergency with high morbidity and mortality. This single center study is aimed to assess changes of serum biochemical biomarkers after seizure, and their associations with the development of CSE.MethodsFrom January 2015 to October 2016, a total of 57 CSE patients, and 30 healthy controls without central nervous system diseases were enrolled in Children’s Hospital of Soochow University. CSE patients were further divided into viral encephalitis (VEN, 13 cases), primary generalized epilepsy (PGE, 30 cases), and complex febrile seizures (CFS, 14 cases). The levels of serum biochemical biomarkers were measured using the corresponding commercial ELISA kits. Logistic regression analysis was performed to identify the associations between these biomarkers and diseases.ResultsAt the 1st and 4th day of CSE, neuron-specific enolase (NSE; 1st day: 20.553 ± 5.360, 4th day: 10.094 ± 3.426) and vascular endothelial growth factor (VEGF; 1st day: 153.504 ± 31.246, 4th day: 138.536 ± 25.221) in the CSE group were increased compared to the control (NSE: 6.138 ± 1.941; VEGF: 119.210 ± 31.681). Both the levels of S-100 calcium binding protein B (S-100B; 1st day: 0.738 ± 0.391) and C-reactive protein (CRP; 1st day: 11.128 ± 12.066) were elevated at 1st day of CSE (S-100B: 0.387 ± 0.040; CRP: 3.915 ± 2.064). For glial fibrillary acidic protein (GFAP), it was remarkably upregulated at 4th day of CSE (3.998 ± 1.211). NSE (P = 0.000), S-100B (P = 0.000), CRP (P = 0.011), and VEGF (P = 0.000) at 1st day of CSE, and NSE (P = 0.000), VEGF (P = 0.005), and GFAP (P = 0.000) at 4th day of CSE were significantly associated with the occurrence of CSE. Besides, NSE (P = 0.002), S-100B (P = 0.001), and VEGF (P = 0.002) at 4th day of CSE were significantly associated with VEN.ConclusionsThe levels of serum NSE, S-100B, CRP, VEGF, and GFAP are associated with CSE.

Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management.

Evolution toward brain death (BD) in out-of-hospital cardiac arrest patients with targeted temperature management (TTM) provides opportunities for organ donation. However, knowledge regarding BD in these patients is limited. We retrospectively analyzed the TTM registry of one hospital where life-sustaining therapy was not withdrawn. In-hospital death patients were categorized into BD and non-BD groups. We explored the process of evolution toward BD and its predictors by comparing the serial measurements of clinical variables and the results of various prognostic tests between the two groups. Of the 121 patients who died before hospital discharge, 19 patients (15.7%) developed BD at a median of 6 (interquartile range, 5.0–7.0) days after cardiac arrest. Four patients with pupillary light reflexes at 48 h eventually developed BD. The area under the curves of the gray-to-white matter ratio (GWR) on early brain computed tomography images and the level of S100 calcium-binding protein B (S100B) at 72 h were 0.67 (95% CI, 0.55–0.77) and 0.70 (95% CI, 0.55–0.83), respectively. In conclusion, approximately one-sixth of all in-hospital deaths were diagnosed with BD at a median of 6 days after cardiac arrest. The use of GWR and serial S100B measurements may help to screen potential BD.

Ruscogenin alleviates cognitive dysfunction by inhibiting the activation of isoflurane-induced NLRP3 inflammasome in aged mice

Ruscogenin exerts an anti-inflammatory effect in the pathogenesis of various human diseases, including pulmonary hypertension, acute lung injury, acute pancreatitis and cerebral ischemia. Its role in isoflurane-induced rats with postoperative cognitive dysfunction (POCD) was investigated in this study. Aged rats were exposed to isoflurane for establishing a model of POCD, and administered with ruscogenin by gavage. Cognitive dysfunction was evaluated by the Morris water maze test. Hematoxylin and Eosin (H&amp;E) staining was designed to assess neuronal damage. Markers of brain damage and neuroinflammation were detected by enzyme-linked-immunosorbent serologic assay. Isoflurane exposure caused impaired cognitive function by increasing escape latency, decreasing the time taken for crossing target and time in target quadrant. However, administration of ruscogenin reversed these cognitive dysfunctions. Abnormal morphological phenomena on neurons and enhanced levels of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) were identified in mice post-isoflurane exposure. Administration of ruscogenin ameliorated the neuronal morphological damages and reduced the levels of S-100β and NSE in the hippocampi of isoflurane-induced aged mice. Ruscogenin also attenuated isoflurane-induced enhancements in the levels of Interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha in the hippocampi of mice. Isoflurane-induced enhancements in the mRNA expression levels of NLR family pyrin domain containing 3 (NLRP3), ASC, IL-1β and IL-18 proteins were also restored by administration of ruscogenin. Ruscogenin exerted neuroprotective effects against isoflurane-induced cognitive dysfunction and neuroinflammation through blocking of NLRP3 pathway.

The Levels of Circulating MicroRNAs at 6-Hour Cardiac Arrest Can Predict 6-Month Poor Neurological Outcome.

Early prognostication in cardiac arrest survivors is challenging for physicians. Unlike other prognostic modalities, biomarkers are easily accessible and provide an objective assessment method. We hypothesized that in cardiac arrest patients with targeted temperature management (TTM), early circulating microRNA (miRNA) levels are associated with the 6-month neurological outcome. In the discovery phase, we identified candidate miRNAs associated with cardiac arrest patients who underwent TTM by comparing circulating expression levels in patients and healthy controls. Next, using a larger cohort, we validated the prognostic values of the identified early miRNAs by measuring the serum levels of miRNAs, neuron-specific enolase (NSE), and S100 calcium-binding protein B (S100B) 6 h after cardiac arrest. The validation cohort consisted of 54 patients with TTM. The areas under the curve (AUCs) for poor outcome were 0.85 (95% CI (confidence interval), 0.72–0.93), 0.82 (95% CI, 0.70–0.91), 0.78 (95% CI, 0.64–0.88), and 0.77 (95% CI, 0.63–0.87) for miR-6511b-5p, -125b-1-3p, -122-5p, and -124-3p, respectively. When the cut-off was based on miRNA levels predicting poor outcome with 100% specificity, sensitivities were 67.7% (95% CI, 49.5–82.6), 50.0% (95% CI, 32.4–67.7), 35.3% (95% CI, 19.7–53.5), and 26.5% (95% CI, 12.9–44.4) for the above miRNAs, respectively. The models combining early miRNAs with protein biomarkers demonstrated superior prognostic performance to those of protein biomarkers.

Effects of Vitamin C and Dimethylsulfoxide (Dmso) on Neuro-Behaviour, Apoptosis and oxidative stress in ischaemic stroke induced rats

Background: Researches over the years have identified excitotoxicity, oxidative stress, inflammation and cell death as key contributors underlying progression of lesion in ischaemic stroke (IS). This study reports the effect of vitamin C and dimethylsulfoxide (DMSO) in the management of ischaemic stroke (IS) in Wistar rats. Method: Forty rats were divided into four groups of ten rats each. Groups 1, 2 and 3 were induced with IS by middle cerebral artery occlusion (MCAO). Anxiety like behavior and locomotor activity assessments were carried out. Group 1was treated with vitamin C (67.5mg/kg) and group 2 with DMSO (67.5mg/kg) orally for two weeks. Group 4 was neither induced nor treated. Brain tissue homogenates (cerebral cortex) were assessed for the level of calcium binding protein (S100B), antioxidant enzymes [Superoxide dismutase (SOD), Catalae (CAT), Glutathion peroxidase (GPx)] gene expressions, BCL2, Bax and Caspase3. Result: The results of this study showed that in the IS rats, there was significant (P&lt;0.05) increase in anxiety and a significant (P&lt;0.05) decrease in the locomotor activity. There was also significant (P&lt;0.05) increase in S100B, caspase 3 and Bax expressions, while there was significant (P&lt;0.05) decrease in BCL2. Treatment with vitamin C and DMSO resulted in significant (P&lt;0.05) increase in the locomotor activity and significant (P&lt;0.05) decrease in anxiety. There was significant (P&lt;0.05) increase in the expression of SOD, CAT and GPx genes. Also, there was significant (P&lt;0.05) decrease in S100B level, caspase-3 and Bax expressions, while there was significant (P&lt;0.05) increase in BCL2. Conclusion: Conclusively, the results of this research highlighted the potentials for the use of vitamin C and DMSO in the management of IS. Keywords: Stroke; Antioxidant; Locomotor; Neuro-Behavioural; Dimethylsulfoxide Apoptosis; Oxidative Stress

Levels of S100 calcium binding protein B (S100B), neuron-specific enolase (NSE), and cyclophilin A (CypA) in the serum of patients with severe craniocerebral injury and multiple injuries combined with delirium transferred from the ICU and their prognostic value.

To analyze the levels of S100 calcium binding protein B (S100B), neuron-specific enolase (NSE), and cyclophilin A (CypA) in the serum of patients with severe craniocerebral injury combined with delirium and multiple injuries transferred from the intensive care unit (ICU), and their prognostic value. The data of 98 patients with severe craniocerebral injury combined with delirium and multiple injuries admitted to our hospital from January 2018 to May 2019 were retrospectively analyzed as the study group. The differences in serum S100B, NSE, and CypA levels in each group were compared, and the deaths of the study group during follow-up were counted. The levels of S100B, NSE, and CypA in the study group were higher than those in the control group (P<0.05). The mortality rate of the 98 patients with severe craniocerebral injury combined with delirium and multiple injuries transferred from the ICU was 37.76%. Furthermore, the levels of S100B, NSE, and CypA in the death group were higher than those in the survival group (P<0.05). Glasgow Coma Score (GCS) score ≤5 points, Injury Severity Score (ISS) score >25 points, multiple organ dysfunction syndrome, and increased levels of S100B, NSE, and CypA were independent risk factors that affected the prognosis of patients with severe craniocerebral injury combined with delirium and multiple injuries transferred from the ICU (P<0.05). The average survival times of the high S100B level group, the high NSE level group, and the high CypA level group were shorter than those of the low-level groups (P<0.05). The levels of S100B, NSE, and CypA in serum were closely related to the prognosis of patients with severe craniocerebral injury combined with delirium and multiple injuries transferred from the ICU. They can be used as molecular markers for predicting the prognosis of patients, and may serve as potential targets for treatment.

Serum levels of neurofilament light chain, neuron-specific enolase and S100 calcium-binding protein B during acute bacterial meningitis: a prospective cohort study

Purpose Acute bacterial meningitis (ABM) is a severe disease with an overall poor outcome. Neurofilament (NFL) has shown to be a promising biomarker of neuroaxonal injury in various neurological disorders but has not been investigated in ABM. The aims of this study were (i) to obtain a temporal profile of NFL, neuron-specific enolase (NSE) and S100B in serum during ABM, and (ii) to evaluate their use as biomarkers of severity (Glasgow coma score) and prognosis (Glasgow Outcome Score, GOS and death) in severe ABM. Methods Fifteen adults with severe community-acquired ABM who were admitted to the intensive care unit (ICU) and fulfilled the inclusion criteria were included. Lumbar puncture and blood tests were performed on admission, and blood tests were performed three times daily during the ICU stay. GOS was obtained day 30. Results Serum NFL was significantly elevated in ABM patients compared to healthy controls, both at admission and throughout the observation period (p < .01). NFL increased significantly from day 1 up to day 3–6 (p < .0001), peaking day 6. NSE increased significantly from admission up to day 3 (p < .01). At day 5–6, the serum values were not significantly different from values at admission. The highest median serum value of S100B was observed at admission (0.10 µg/L, IQR 0.06–0.14), significantly decreasing day 4–6 (p < .05). None of the investigated biomarkers revealed significant correlation with severity and prognosis. Conclusion This study represents a first clinical observation of the temporal profile of NFL in serum, in severe ABM. No correlation with severity or prognosis.

The neuroprotective action of lenalidomide on rotenone model of Parkinson's Disease: Neurotrophic and supportive actions in the substantia nigra pars compacta

Lenalidomide is a centrally active thalidomide analog that has potent anti-inflammatory and antiangiogenic activities. Currently, it is primarily used in the treatment of multiple myeloma and myelodysplastic syndromes. However, recent studies have revealed in addition to neuroprotection and neuromodulation of lenalidomide. Because of this combination of inflammation and neuro-immunogenic properties, lenalidomide is considered as a high potential compound for the treatment of neurodegenerative diseases. Despite intensive research during the last decade, the role of neurotrophic elements in the effect of lenalidomide is still not well understood. Therefore, in the current study, the effects of lenalidomide on neurodegeneration were investigated in a rotenone model of Parkinson’s disease (PD) rat model. The PD rat model was generated by rotenone injection into the substantia nigra pars compacta (SNpc). After validation of the PD model, the rats were treated with lenalidomide (100 mg/kg) for 28 days. Our data shows that lenalidomide alleviated rotenone-induced motor impairments and deficits in dopamine-related behaviors and resulted in increased levels of tumor necrosis factor-α and calcium-binding protein B in the SNpc. Moreover, chronic lenalidomide treatment resulted increase in transforming growth factor immunoreactivity and brain derived neurotrophic factor expression in the SNPc. In addition, chronic treatment mitigated tyrosine hydroxylase expression prevented the rotenone-induced decrease in dopamine levels, and consequently a decrease in caspase-3/9 immunoreactivity. This thus shows that chronic lenalidomide treatment improves neuronal survival. Together with our data demonstrate that lenalidomide, in addition to its anti-inflammatory and immunomodulatory actions, is also capable of increasing neurotrophic factors in the SNpc, thereby preventing rotenone-induced motor impairments.

Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

Glucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated cognitive decline. However, there is an issue of poor compliance by multiple daily subcutaneous injections for sufficient glycemic control due to their short duration, and neuroprotective actions were not fully studied, yet. In this study, using the prepared exendin-4 fusion protein agent, we investigated the pharmacokinetic profile and the role of this GLP-1 mimetics on memory deficits in a high-fat diet (HFD)/streptozotocin (STZ) mouse model of type 2 diabetic mellitus. After induction of diabetes, mice were administered weekly by intraperitoneal injection of GLP-1 mimetics for 6 weeks. This treatment reversed HFD/STZ-induced metabolic symptoms of increased body weight, hyperglycemia, and hepatic steatosis. Furthermore, the impaired cognitive performance of diabetic mice was significantly reversed by GLP-1 mimetics. GLP-1 mimetic treatment also reversed decreases in GLP-1/GLP-1 receptor expression levels in both the pancreas and hippocampus of diabetic mice; increases in hippocampal inflammation, mitochondrial fission, and calcium-binding protein levels were also reversed. These findings suggest that GLP-1 mimetics are promising agents for both diabetes and neurodegenerative diseases that are associated with increased GLP-1 expression in the brain.

Glial injury in neurotoxicity after pediatric CD19-directed chimeric antigen receptor T cell therapy.

To test whether systemic cytokine release is associated with central nervous system inflammatory responses and glial injury in immune effector cell-associated neurotoxicity syndrome (ICANS) after chimeric antigen receptor (CAR)-T cell therapy in children and young adults. We performed a prospective cohort study of clinical manifestations as well as imaging, pathology, CSF, and blood biomarkers on 43 subjects ages 1 to 25 who received CD19-directed CAR/T cells for acute lymphoblastic leukemia (ALL). Neurotoxicity occurred in 19 of 43 (44%) subjects. Nine subjects (21%) had CTCAE grade 3 or 4 neurological symptoms, with no neurotoxicity-related deaths. Reversible delirium, headache, decreased level of consciousness, tremor, and seizures were most commonly observed. Cornell Assessment of Pediatric Delirium (CAPD) scores ≥9 had 94% sensitivity and 33% specificity for grade ≥3 neurotoxicity, and 91% sensitivity and 72% specificity for grade ≥2 neurotoxicity. Neurotoxicity correlated with severity of cytokine release syndrome, abnormal past brain magnetic resonance imaging (MRI), and higher peak CAR-T cell numbers in blood, but not cerebrospinal fluid (CSF). CSF levels of S100 calcium-binding protein B and glial fibrillary acidic protein increased during neurotoxicity, indicating astrocyte injury. There were concomitant increases in CSF white blood cells, protein, interferon-γ (IFNγ), interleukin (IL)-6, IL-10, and granzyme B (GzB), with concurrent elevation of serum IFNγ IL-10, GzB, granulocyte macrophage colony-stimulating factor, macrophage inflammatory protein 1 alpha, and tumor necrosis factor alpha, but not IL-6. We did not find direct evidence of endothelial activation. Our data are most consistent with ICANS as a syndrome of systemic inflammation, which affects the brain through compromise of the neurovascular unit and astrocyte injury. ANN NEUROL 2019.

Evaluation of Cerebral Blood Flow Alterations and Acute Neuronal Damage due to Water-Pipe Smoking

Background:Although water-pipe smoking is a great public health problem, data regarding the acute and chronic effects and the degree of toxin exposure are limited. While water pipe-related malignancy, pulmonary, infectious, cardiac effects, infertility, and biological effects have been described in a meta-analysis, there are no studies in the literature about its neurologic effects.Aims:To evaluate water pipe-related acute neurological effects and cerebral blood flow through transcranial Doppler ultrasonography and serum S100 calcium binding protein calcium binding protein level measurements.Study Design:Prospective observational study.Methods:Vital signs and baseline carboxyhemoglobin and S100 calcium binding protein levels, cerebral flood changes with transcranial Doppler ultrasound were evaluated and recorded before and after water-pipe smoking.Results:The mean age of the 31 volunteers was 30.61 (±5.67) years, and 24 of them (77.42%) were male. A statistically significant difference was determined in heart rate, oxygen saturation, systolic and diastolic arterial pressure values before and after water-pipe smoking (p<0.001, p=0.035, p=0.009, p=0.021, respectively). Mean carboxyhemoglobin level was 2.68% (±1.68) before, 14.97% (±4.83) after water-pipe smoking (p<0.001). The S100 calcium binding protein level was 25.05 μ/mL (±8.34) at the beginning, 40.71 μ/mL (±14.06) after water-pipe smoking (p<0.001). An increase was determined in peak, and median middle, anterior and posterior cerebral artery blood flow rates, and a decrease was determined in both the pulsatility index and resistivity index values after water-pipe smoking using transcranial Doppler ultrasound.Conclusion:Cerebral vasodilation develops due to the increase in cerebral blood flow rate and the decrease in pulsatility index, resistivity index values, and the elevation in carboxyhemoglobin, S100 calcium binding protein level indicates that water-pipe smoking leads to neuronal damage in the acute period.