Neuron-specific Enolase Activity Research Articles

Study on the role of tissue-specific and non-specific autoantibodies, matrix metalloproteinase-3 and neuron-specific enolase enzymes in the exacerbation of autoimmune thyroiditis

The aim of the study was to examine the involvement of tissue-specific and non-specific autoantibodies, matrix metalloproteinase-3 and neuron-specific enolase (NSE) enzymes in the development and exacerbation of autoimmune thyroiditis. Materials and methods. The study enrolled 170 patients with autoimmune thyroiditis (64 males and 106 females aged 18 to 64 years) to comprehensively examine their humoral immune response indicators (IgA, M, G), organ-specific (Ab-TG, Ab-TPO) and organ-non-specific antibodies (Ab-DNA), metalloproteinase-3 and NSE activity. The control group consisted of 65 individuals without thyroid pathologies or other autoimmune diseases, aged 20 to 65 years (26 males and 39 females). Results. The study has demonstrated changes in the levels of organ-specific and organ-nonspecific antibodies and statistically significantly increased metalloproteinase-3 activity in patients with autoimmune thyroiditis. Positive correlations have been found between elevated levels of IgG, Ab-TG, Ab-TPO, Ab-dsDNA and NSE activity. Negative correlations have been observed between NSE activity and IgA concentrations. Conclusions. Elevated titers of anti-DNA autoantibodies may indicate an aggravation of the autoimmune process due to cellular structure damage, resulting in gland dysfunction. The findings also suggest that metalloproteinase-3, a marker predicting thyroid tissue damage, may negatively impact the immune response induction, ultimately affecting the activity of neuron-specific enolase. The data have shown that studying biochemical indicators such as antinuclear antibodies (ANA), anti-DNA antibodies, metalloproteinase-3 and neurodegenerative indicators could provide informative markers to determine the nature of the disease development and worsening.

Protective and therapeutic effects of okra seed in acute nontraumatic brain injury

Aim The purpose of this study was to examine the protective and therapeutic effects of okra (Abelmoschus esculentus [AE]) seed extract, with its known antioxidant, immunomodulatory, and anti-inflammatory properties, in an acetaminophen (paracetamol, N-acetyl- para-aminophenol)-induced model of hepatotoxicity and subsequent acute non-traumatic brain damage. Material and Method Forty male Wistar rats were randomly divided into five equal groups, control, paracetamol (P), okra seed extract (AE), okra seed extract + paracetamol (P + AE), and okra seed extract + paracetamol + N-acetyl cysteine (NAC) (P + AE + N). AE was administered by oral gavage through a gastric tube at 600 mg/kg/day for seven days. On the eighth day of the procedure, a single 1 g/kg dose of paracetamol and 300 mg/kg NAC were injected via the intraperitoneal route 1.5 h after AE administration. Rat tissue specimens were subsequently subjected to biochemical and histopathological analyses. Levels of markers such as S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), and matrix membrane metalloproteinase-9 (MMP-9) were investigated from rat serum specimens. Malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured to determine oxidant-antioxidant status. Results S100B, NSE, MMP-9, MDA levels, and SOD enzyme activities were examined using biochemical methods. MDA levels were significantly lower in the P + AE group and MMP-9 levels in the AE, P + AE, and P + AE + N groups compared to the P group. Histopathological examination results supported the biochemical findings Conclusion Okra seed extract exhibits a protective and therapeutic effect against non-traumatic brain damage resulting from acute paracetamol intoxication. We think that this benefit of AE derives from its antioxidant property.

Astaxanthin Ameliorates Diabetic Retinopathy in Swiss Albino Mice via Inhibitory Processes of Neuron-Specific Enolase Activity

Retinopathy is one of the most common complications of diabetes mellitus. Diabetic retinopathy (DR) occurs due to microvascular damage in retinal tissues provoked by high blood sugar levels. The available drugs for DR are limited. Astaxanthin (AST) has anti-hypertensive, anti-obesity, and anti-diabetic properties. However, the therapeutic effect of AST on DR remains elusive. The present study is designed to investigate the effects of AST on DR via inhibition of neuron-specific enolase (NSE) activity. DR was induced by the administration of streptozotocin (STZ, 35 mg/kg: intraperitoneal; and 20 μL of STZ: intravitreal) in mice. AST (10 and 20 mg/kg) was administered orally (p.o.) for 21 days. The DR associated visual changes were assessed at different time intervals via optokinetic motor response (OMR) and penta-maze (PM) tests. Blood glucose level as well as retinal catalase, lactate dehydrogenase (LDH), & neuron-specific enolase (NSE) were estimated. The reference drug i.e., dexamethasone (DEX, 10 mg/kg; p.o.) was administered for 21 days. The administration of AST showed significant ameliorative potential in DR. Hence, AST can be used as a natural medicine for the management of DR due to its potential antioxidant, anti-diabetic, and NSE inhibitory properties.

Relationship of serum ATPase activity and the levels of neuron- specific enolase, S100B and B-cell lymphoma/leukemia-2 with cognitive function after epileptic seizure.

To analyze the relationship of serum ATPase activity and the levels of neuron-specific enolase (NSE), S100B protein and B-cell lymphoma/leukemia (Bcl)-2 with cognitive function in patients after epileptic seizure. A total of 65 epilepsy patients were enrolled as the epilepsy group from the hospital between May 2017 and February 2019. A control group was formed by 30 healthy volunteers at the same period and in the same area whose basic data matched with those of the epileptic patients. Cognitive function was evaluated using the Montreal Cognitive Assessment Form (MoCA). Time and frequency of epileptic seizures were recorded in epileptic group. Within 6 hours following the attack, blood tests were carried out to measure the hydrolysis rates of serum adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphodiesterase (PDE) activity, and levels of serum NSE, S100B and Bcl-2. The relationship of these indexes with the time of epileptic seizure and MoCA total score was analyzed. The epilepsy group included 18 cases (27.69%) with cognitive dysfunction. The time and frequency of epileptic seizure in the patients with cognitive dysfunction was significantly higher than that of patients without cognitive dysfunction, while the total MoCA score was significantly lower with cognitive dysfunction than that without (P<0.05). The total MoCA score of epileptic patients with and without cognitive dysfunction was significantly lower than that of the control group (P<0.05). The hydrolysis rates of ATP, ADP and AMP, PDE activity, and serum NES, S100B and Bcl-2 levels in patients with cognitive dysfunction were significantly higher than those without cognitive dysfunction (P<0.05). The above serum indexes of the patients were significantly higher than those of people in the control group (P<0.05). Spearman's correlation analysis showed that hydrolysis rates of serum ATP, ADP and AMP, PDE activity, and serum NES, S100B and Bcl-2 levels were positively correlated with time and frequency of epileptic seizure (P<0.05), and negatively correlated with total MoCA score (P<0.05). The cognitive function of epilepsy patients is significantly decreased compared with that of healthy individuals. Serum ATPase activity, along with serum NES, S100B and Bcl-2 levels, is associated with time and frequency of epileptic seizure and cognitive function after attack.

Investigation of the infusion solutions of different qualitative composition influence on the dynamics of neuron specific enolase activity in patients with acute ischemic stroke

At the moment, the question remains insufficiently studied what kind of infusion fluids or their combination should be preferred in patients with acute ischemic stroke (AIS) to provide intensive care. Purpose. To investigate the dynamics of neuron-specific enolase (NSE) against the background of the iso-osmolar 0.9 % NaCl solution, colloid iso-osmolar fluid HES 130, colloid hyperosmolar fluid HAES-LX-5 % and hyperosmolar fluid mannitol application in AIS. Materials and methods. The study included 32 patients with AIS. As the studied solutions were used: colloid hyperosmolar HAES-LX-5 % (Gekoton), colloid iso-osmolar hydroxyethyl crystal 6 % 130/04 (HES 130), hyperosmolar mannitol 15 %, and iso-osmolar 0.9 % NaCl. The control group consisted of patients receiving only 0.9 % NaCl, the comparison groups – the patients receiving 0.9 % NaCl + HES 130 or 0.9 % NaCl + HAES-LX-5 %, or 0.9 % NaCl + mannitol. NSE activity was used as a marker of cerebral ischemia at the corresponding time (the 1st, 4th and 7th days). Results. An increase in NSE (P < 0.05) was observed in the 0.9 % NaCl group at the 7th day of stroke. A similar dynamics of NSE elevation was in the group with mannitol (P < 0.05), as well as in the control group. A 17.3 % decrease in the NSE activity was noted in the application of HES 130 at the end of observation relative to the 1st day. The NSE activity decreased by 34.6 % (P < 0.05) on the 7th day in comparison with the 1st day in the HAES-LX-5 % group and was significantly less than in the control group, groups of HES 130 and mannitol – on average 2.88 times and 30.3 %, 39.8 %, respectively. Conclusions . The use of 0.9 % NaCl or 0.9 % NaCl + mannitol within 7 days in patients with AIS in addition to basic therapy was accompanied by an increase in NSE. Infusion of 0.9 % NaCl + HES 130 or 0.9 % NaCl + HAES-LX-5 % was accompanied by a decrease in NSE activity at the 7th day of treatment, herewith the HAES-LX-5 % group showed the best dynamics of NSE activity decreasing (P < 0.05).

Dynamic of activity of neuron-specific enolase and titres of protein S100 in blood serum of patients with iatrogenic-compression-toxic lesions of the lower alveolar nerve for different therapeutic tactics

Optimization of the tactics for the patients with iatrogenic-compression-toxic lesions of the lower alveolar nerve (ICT LAN) - is an urgent task of modern medicine and dental service in particular. The solution of the above problem can be achieved by involving neuroprotective agents with a blocking effect on the excessive activity of NMDA receptors in the therapeutic tactics. This can prevent further nerve damage and trigeminal neurons site and restore the activity of the cells due to ischemic-hypoxic process in a state of hibernation. Objective — to conduct a comparative, dynamic (within 30 days) evaluation of the activity and level of neuromarkers (neuron-specific enolase and protein S100) in blood serum of patients with iatrogenic-compression-toxic lesions of the lower alveolar nerve for different therapeutic tactics, including with the addition of amantadine hydrochloride to therapy. The study involved male patients, aged 20 to 60 years, without concomitant dental pathology ICT LAN, which came with overfilling into the mandibular canal fillings material Foredent or AH-Plus. On the 7th, 14th and 30th days of the pathology in the blood serum of such patients, the isozyme determination of the enolase activity and the titration of the S100 protein were performed on the background of different therapeutic tactics, including when combining standard therapy with neuroprotector Neomidantan. Comparing neuromarker dynamics in groups without neuroprotective support (II and III) and in the conditions of appointment of Neomidantan, one can conclude that the last drug causes the most powerful de-escalation and activity of NSE and titers of the S100 protein. Therefore, Neomidantan shows neuroprotective effect on system inferior alveolar nerve/trigeminal neurons site and its function in patients with ICT LAN helps preserve morphological and functional integrity of this system, which is particularly manifested in the 30th day of therapy. Summing up the neuromarkers changes in the ICT LAN on the 30th day of observation, depending on the therapeutic tactic, the following variation series can be constructed: ICT LAN+ protocol therapy (II group) &gt; ICT LAN+ protocol surgical and therapeutic treatment (ІІІ group) &gt; ICT LAN + protocol therapy + Neomidantan (IV) &gt; ICT LAN + protocol surgical and therapeutic treatment + Neomidantan (V group).

New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection.

Neurodegeneration is a complex process that leads to irreversible neuronal damage and death in spinal cord injury (SCI) and various neurodegenerative diseases, which are serious, debilitating conditions. Despite exhaustive research, the cause of neuronal damage in these degenerative disorders is not completely understood. Elevation of cell surface α-enolase activates various inflammatory pathways, including the production of pro-inflammatory cytokines, chemokines, and some growth factors that are detrimental to neuronal cells. While α-enolase is present in all neurological tissues, it can also be converted to neuron specific enolase (NSE). NSE is a glycolytic enzyme found in neuronal and neuroendocrine tissues that may play a dual role in promoting both neuroinflammation and neuroprotection in SCI and other neurodegenerative events. Elevated NSE can promote ECM degradation, inflammatory glial cell proliferation, and actin remodeling, thereby affecting migration of activated macrophages and microglia to the injury site and promoting neuronal cell death. Thus, NSE could be a reliable, quantitative, and specific marker of neuronal injury. Depending on the injury, disease, and microenvironment, NSE may also show neurotrophic function as it controls neuronal survival, differentiation, and neurite regeneration via activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways. This review discusses possible implications of NSE expression and activity in neuroinflammation, neurodegeneration, and neuroprotection in SCI and various neurodegenerative diseases for prognostic and therapeutic potential.

Neuron Specific Enolase in Relation to Chitotriosidase and Heat Shock Protein 72: A Network of Integrated Predictive Biomarkers in Preeclampsia and Eclampsia

Background: Preeclampsia and eclampsia are life-threatening conditions with increasing incidence. Since, Neuron specific enolase (NSE) is a vital biomarker for neuronal damage, our study aimed to investigate its role in relation to macrophage activation, angiogenesis, heat shock protein 72 and antioxidant biomarkers in preeclampsia and eclampsia patients. Methods: This study included 45 pregnant women; divided into 3 groups. Group I included 15 healthy pregnant women (control group), Group II included 15 preeclampsia patients and Group III included 15 eclampsia patients. They were subjected to measurement of plasma of NSE, insulin growth factor-1 (IGF-1), nitric oxide (NO), heat shock protein 72 (HSP72) levels and chitotriosidase activity in addition to serum paraoxonase activity. Results: The study showed significant increased levels of NSE, IGF-1, HSP72, and chitotriosidase activity in group II and III when compared to control group with the highest levels in group III. On the other hand, it showed significant decrease in NO level and paraoxonase activity in group II and III when compared to control group with lowest level in group III. Conclusion: Based on our findings, NSE can be used as a reliable biomarker to predict the outcome of preeclampsia and early prediction of eclapmsia to avoid serious complications.

Improved monitoring dynamics through use of a tethered enzyme biosensor to detect and quantify neuron-specific enolase activity levels in biofluids

Improved monitoring dynamics through use of a tethered enzyme biosensor to detect and quantify neuron-specific enolase activity levels in biofluids

Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a complex debilitating condition leading to permanent life-long neurological deficits. The complexity of SCI suggests that a concerted multi-targeted therapeutic approach is warranted to optimally improve function. Damage to spinal cord is complicated by an increased detrimental response from secondary injury factors mediated by activated glial cells and infiltrating macrophages. While elevation of enolase especially neuron specific enolase (NSE) in glial and neuronal cells is believed to trigger inflammatory cascades in acute SCI, alteration of NSE and its subsequent effects in acute SCI remains unknown. This study measured NSE expression levels and key inflammatory mediators after acute SCI and investigated the role of ENOblock, a novel small molecule inhibitor of enolase, in a male Sprague-Dawley (SD) rat SCI model. Serum NSE levels as well as cytokines/chemokines and metabolic factors were evaluated in injured animals following treatment with vehicle alone or ENOblock using Discovery assay. Spinal cord samples were also analyzed for NSE and MMPs 2 and 9 as well as glial markers by Western blotting. The results indicated a significant decrease in serum inflammatory cytokines/chemokines and NSE, alterations of metabolic factors and expression of MMPs in spinal cord tissues after treatment with ENOblock (100µg/kg, twice). These results support the hypothesis that activation of glial cells and inflammation status can be modulated by regulation of NSE expression and activity. Analysis of SCI tissue samples by immunohistochemistry confirmed that ENOblock decreased gliosis which may have occurred through reduction of elevated NSE in rats. Overall, elevation of NSE is deleterious as it promotes extracellular degradation and production of inflammatory cytokines/chemokines and metabolic factors which activates glia and damages neurons. Thus, reduction of NSE by ENOblock may have potential therapeutic implications in acute SCI.

Activity of neuron-specific enolase in patients with acute ishemic stroke on the background of correction of infusion solutions

The article analyzes the impact of a single course of treatment with various infusion solutions on the intensity of the flow of destructive changes in the neurons of the brain to the dynamics of the activity of the neuron-specific enolase, which is an early marker of damage of the nervous tissue. The level of neuron-specific enolase in serum of patients with acute stroke is correlated with the volume of cerebral infarction. To a thorough determine the presence of the protective effect in the infusion solutions on the brain was interest to investigate the effect of a single course of treatment with various solutions on the intensity of the flow of destructive changes in the neurons of the brain with the dynamics of neuron-specific enolase in acute disorder of cerebral circulation. Analyzed isoosmolar 0.9% NaCl solution and colloidal isoosmolar hydroxyethylstarch 130/04 solution administered intravenous drip in a conventionally effective dose of 2.5 ml / kg p 2 / day (5 ml / kg per day) (determined experimentally) immediately upon confirmation of the diagnosis and further a daily basis and every 12 h for 7 days. Control group were patients treated with infusion solutions only 0.9% NaCl, control group – 0.9% NaCl + hydroxyethylstarch 130/04. Using of the isoosmolar 0.9% NaCl solution for 7 days in addition to standard therapy promotes a statistically significant increase in the activity of the neuron-specific enolase on the seventh day of stroke, which is associated with increasing of necrotic tissue in the ischemic area of the brain in patients with acute disorder of cerebral circulation in ischemic type. Infusion therapy in patients with acute disorder of cerebral circulation in ischemic type with isoosmolar 0,9% NaCl + colloid isoosmolar solution of hydroxyethyl starch 130/04, against a background of standard therapy, been accompanied by a significant decrease in the neuron-specific enolase compared with the control group which indicates the presence in hydroxyethyl starch 130/04 corrective influence on the dynamics of the processes of neuronal death in acute ischemic stroke. A possible mechanism of protective effect of hydroxyethyl starch 130/04 implemented by improving perfusion of the penumbra, the disclosure of collaterals, properties of endothelial protection in acute disorder of cerebral circulation.

Neuron specific enolase as a measure of the efficacy of mexidol in patients with neurologic complications of primary hypothyroidism

To evaluate the activity of neuron specific enolase (NSE) in patients with primary hypothyroidism (PGT) treated with mexidol. Patients with PGT (n=110) were examined before and after treatment. Neuropsychological and neurological status of the patients was studied. To assess the status of the peripheral nervous system, electroneuromyography was performed and serum NSE level was determined. The NSE activity depended on gender, age of the patient, duration of endocrinopathy and presence/absence of neurological symptoms. The clear positive dynamics of the majority of the parameters studied was noted during mexidol treatment. The efficacy of antioxidant therapy in these patients was confirmed.

Dysregulation Of Thrombotic and Hemostatic Factors In End Stage Renal Disease

Introduction Increased cardiovascular events occur in ESRD patients on maintenance hemodialysis. The objective of this study was to utilize newly introduced cardiac biomarker chips and immunoenzymatic methods, profiling various biomarkers of inflammation and thrombogenesis in a defined ESRD patient population. Material and Methods Blood samples from seventy two ESRD patients were drawn prior to maintenance hemodialysis. Commercially available ELISA kits for Tissue Plasminogen Activator – Plasminogen Activator Inhibitor Type-1 complex (tPA-PAI-1 complex), Plasminogen Activator Inhibitor Type-1 (PAI-1), Myeloperoxidase, (MPO), Thrombomodulin, (TM), Interleukin-1 beta (IL-1β), Anti-Annexin V, human sL-selectin, and Inter-Cellular Adhesion Molecule 1 (ICAM-1). Functional methods were used for measuring Antithrombin and Von Willebrand factor (vWF) activity were used. The biochip arrays (Randox, Evidence System, United Kingdom)for cardiac markers, included creatine kinase-MB (CK-MB), Myoglobin (Myo), Heart-type fatty acid binding protein (hFABP) and cardiac troponin I (cTn1). The cerebral array included C-reactive protein (CRP), D-Dimer (DDMER), Neuron Specific Enolase (NSE), Neutrophil Gelatinase-Associated Lipocalin (NGAL), soluble Tumor Necrosis Factor Receptor 1 (TNFRI) and Thrombodulin (TM). Results ESRD patients showed assay dependent decrease in markers such as tPA-PAI-1, Anti-Annexin V, L-selectin and Antithrombin activity (ranging from 18 to 46%). The levels for MPO, TM, CK-MB, MYO, FABP, CRP, DDMER, NSE, NGAL, TNFR1, and vWF activity all showed a significant increase in the ESRD patients (ranging from 25%-5587%). No changes were observed in the IL-1B, ICAM1, or cTn1 in ESRD patients compared to normal groups. Conclusions These studies underscore the role of inflammatory and thrombotic mediators in ESRD. The cardiac biochip array revealed a remarkable elevation of the FABP and as well as a notable increase in MYO. The cerebral array revealed a remarkable elevation of the TNFR1. Disclosures: No relevant conflicts of interest to declare.

Transplantation of differentiated bone marrow stromal cells promotes motor functional recovery in rats with stroke

Objective: To investigate the effects of transplantation into rats with stroke of bone marrow-derived mesenchymal stem cells (MSCs) induced by brain-derived neurotrophic factor (BDNF). Materials and methods: MSCs were harvested from 6-week-old Sprague–Dawley male rats, and transplanted into adult Sprague–Dawley male rats with transient middle cerebral artery occlusion. At 48 hours after stroke, the adult rats, weighing 250–280 g, were injected via the tail vein with 1×107 MSCs or MSCs induced by BDNF (BDNF-MSCs) suspended in 1 ml phosphate-buffered saline. All animals underwent the neurological function test for 14 days. Infarct volume and blood–brain barrier permeability assay were assessed on day 14 post-middle cerebral artery occlusion. Western blotting and immunohistochemical staining were used to detect the protein expression of neuron-specific enolase (NSE). Results: Both BDNF-MSCs and MSCs produced improvement in neurological deficits compared with vehicle controls on day 14 (P<0·05). In particular, the group transplanted with BDNF-MSCs exhibited significant recovery of motor function compared with the group transplanted with MSCs alone (P<0·05). Both BDNF-MSCs and MSCs, but particularly the former, reduced infarct volume, improved blood–brain barrier dysfunction, reduced serum NSE levels, activated the NSE activity, and inhibited neuronal apoptosis in the ischemic boundary zone. Conclusions: BDNF-MSCs might contribute to the motor function improvement partly by reducing neuronal damage via upregulating the NSE expression level and inhibiting neuronal apoptosis.

Combined Estimation of Plasma Cell-free DNA Level and Neuron Specific Enolase Activity as Outcome Predictors of Post-resuscitation Patients

Combined Estimation of Plasma Cell-free DNA Level and Neuron Specific Enolase Activity as Outcome Predictors of Post-resuscitation Patients

Drug-Induced Therapeutic Hypothermia After Asphyxial Cardiac Arrest in Swine

A feasibility study was performed to compare an investigational drug, HBN-1, to forced cooling to induce hypothermia after resuscitation in a translation model of asphyxial cardiac arrest in swine. Serum and cerebral spinal fluid neuron-specific enolase activity (sNSE and csfNSE) were measured after cardiac arrest as surrogate markers of brain injury. In a block design, swine resuscitated from 10 minutes of asphyxial cardiac arrest were infused intravenously with HBN-1 or iced saline vehicle (forced hypothermia [FH]) 5 to 45 minutes after return of spontaneous circulation (ROSC). External cooling in both groups was added 45 minutes after ROSC until hypothermia (T=4°C below baseline) was attained. Esophageal (core) temperature, shivering, cardiopulmonary parameters, and time to hypothermia after ROSC were monitored. sNSE and csfNSE were measured 180 minutes after ROSC. HBN-1 induced hypothermia significantly lowered temperature compared to FH 5-45 minutes after ROSC (p<0.0001). Time to hypothermia was reduced by HBN-1 (93±6 minutes) compared to FH (177±10 minutes) (p<0.0001). HBN-1 sNSE (0.7±1.9 ng/mL) and csfNSE (17.3±1.9 ng/mL) were lower compared to FH (6±1.6 ng/mL) and (49.7±32.0 ng/mL) (p<0.0001, p=0.022, respectively). There was no shivering with HBN-1 cooling while all FH cooled swine shivered (p<0.0001). The time to reach target hypothermia after cardiac arrest was reduced by nearly 50% with HBN-1 compared to the FH method of inducing hypothermia. Moreover, surrogate biomarkers of brain injury were significantly reduced with HBN-1 as compared to FH. While HBN-1-induced hypothermia shows promise for being neuroprotective, survival studies are needed to confirm these preliminary findings.

Level of S100B protein, neuron specific enolase, orexin A, adiponectin and insulin-like growth factor in serum of pediatric patients suffering from sleep disorders with or without epilepsy

BackgroundParoxysmal sleep disorders in children are important from both pathophysiological and clinical point of view. Correct diagnosis is crucial for further management. The aim of the present study was to identify peripheral markers of paroxysmal sleep disorders in children, which could improve diagnostics of these disorders. We compared serum levels of several putative biomarkers of neurological disorders, such as S100B protein, neuron specific enolase (NSE), orexin A, adiponectin, and insulin-like growth factor 1 (IGF-1) in pediatric patients suffering from sleep disturbances with those who additionally to parasomnia revealed also epilepsy. MethodsFifty six children from 1 month to 18 years of age hospitalized in the Pediatric Neurology Clinic, Chair of Children and Adolescent Neurology, participated in this study. Polysomnographic diagnostics was indicated due to sleep disturbances. Examination was performed with the use of polysomnography and videoelectroencephalography Grass device. Blood samples were taken before registration of sleep, after 2.5h of sleep or 0.5h after occurrence of clinical seizures. Concentrations of S100B protein, NSE, orexin A, adiponectin, and IGF-1 were measured by specific ELISA methods. ResultsThe obtained data showed that serum S100B level was significantly increased in children with epilepsy and clinical seizure attacks as compared to patients with parasomnia only. A tendency to enhanced serum S100B level was also seen in epileptic children without clinical seizures during polysomnographic recording. The level of orexin Awas significantly decreased in epileptic children without seizures as compared to the hormone level in parasomnic patients, but was elevated in patients who experienced seizures during polysomnographic examination. As S100B is regarded to be a marker of blood brain barrier leakage and astrocyte damage, the data suggest an increase in BBB permeability in epileptic children, especially during seizure fits. Furthermore, the enhanced S100B serum level without changes in NSE activity may be interpreted rather as an evidence of the elevated secretion of this protein during seizures than of the damage of brain tissue. In contrast to S100B and orexin A level, serum concentration of adiponectin and IGF-1 as well as NSE activity did not significantly differ between the studied groups. ConclusionOut of the five putative biomarkers measured, blood concentration of S100B and orexin Amay be helpful in differentiating parasomnic pediatric patients with and without epilepsy.

Melatonin treatment protects against spinal cord injury induced functional and biochemical changes in rat urinary bladder

Oxidative stress induced by spinal cord injury (SCI) has deleterious effects on the function of several organ systems including the urinary bladder. In this study, we investigated the possible protective actions of melatonin on SCI-induced oxidative damage and urinary bladder dysfunction. Wistar albino rats (n = 24) were divided randomly as control, vehicle- or melatonin (10 mg/kg, ip)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury at T10 was used. Injured animals were given either vehicle or melatonin 15 min postinjury. One week postinjury, each rat was neurologically examined and then decapitated; blood samples were taken to evaluate neuron-specific enolase (NSE) and soluble protein 100β (S-100β). Spinal cord (SC) and urinary bladder samples were taken for functional studies and histological examination or stored for the measurement of malondialdehyde (MDA), glutathione (GSH) and nerve growth factor (NGF) levels and caspase-3 activity. Isometric contractions in bladder strips were induced by carbachol. In the SCI rats, decreased contractile responses of the bladder strips were found to be restored by melatonin treatment. Serum S-100β levels and NSE activities and tissue MDA levels and caspase-3 activities, all of which were elevated in the vehicle-treated SCI animals as compared to the control values, were reversed by melatonin treatment. On the other hand, reduced GSH and NGF levels due to SCI were restored by melatonin treatment. Furthermore, melatonin treatment improved histological findings. These findings suggest that melatonin reduces SCI-induced tissue injury and improves bladder functions through its effects on oxidative stress and NGF.

Neurospecific enolase as a nonspecific neurodegenerative process marker

For the diagnosis and prognosis of various diseases is essential to determine specific markers in blood serum. Neuronspecific enolase (NSE) is a common marker of differentiatedneurons. The aim of the study was to evaluate the activity of NSE in patients with Parkinson's disease (PD) and chronic cerebral ischemia. The study results showed that the activity of NSE varied dependingon sex and age in PD patients, the stage and rate of progression of disease, age debut and severity of cognitive impairment. Thus, determination of NSE in the serum of PD patients should be included in the complex examination of patients with PD, as an additional marker of the neurodegenerative process.

P19 ras Represses proliferation of non-small cell lung cancer possibly through interaction with Neuron-Specific Enolase (NSE)

p19 ras is an alternative splicing product of the proto-oncogene c-H-ras pre-mRNA. In this study, we identified a novel p19 ras -binding protein, Neuron-Specific Enolase (NSE), using the yeast two-hybrid method. NSE is one of the enolase families that convert 2-phospho- d-glycerate (PGA) to phosphoenolpyruvate (PEP) in the glycolysis pathway. In both endogenous and over-expressed systems, we confirmed interactions between p19 ras and NSE via co-immunoprecipitation assay. We also identified the interaction region of p19 ras , which is required for binding with NSE. When full-length p19 ras and C-terminal region are bound to NSE, it inhibits the enzymatic activity of NSE. Furthermore, p19 ras interacted with Enolase α (Enoα) and repressed its enzymatic activity in vitro. p19 ras repressed lung cancer cell proliferation mostly increased by NSE in H1299 cells. Taken together, these results suggest that p19 ras is a novel regulator to suppress cell proliferation in lung cancer through the interaction with NSE.