Release Of Neuron-specific Enolase Research Articles

The neuronal biomarker NSE correlates with the volume of lung contusion in polytraumatized patients.

Severe injuries caused by accidents, like traumatic brain injury (TBI) or thoracic trauma (TT) continue to be the leading cause of death in younger people with relevant socio-economic impact. Fast and targeted diagnostics is essential for further therapy decisions and prognosis. The following study investigates NSE as a potential biomarker for lung injury after blunt TT. This is a retrospective analysis of prospectively collected data in a level-1 trauma center from 2014 to 2020. Serum levels of Neuron-specific Enolase (NSE) and Interleukins (IL-6, IL-10) in injured patients (n = 41) with isolated TT (AISthorax ≥ 3) compared to isolated TBI (AIShead ≥ 3) were assessed from day 0 to 5 after trauma. The extend of lung injury was quantified by Hounsfield scale in CT scans. 30 patients with TT (ISSmed = 20, age 50y ± 17, 83,3% male) and 11 patients with TBI (ISSmed = 25, age 54y ± 17,27,3% male) were included. After TT, NSE concentration increased initially after trauma with a peak value on the day of admission (8.51 ± 3.68 ng/ml) compared to healthy controls (4.51 ± 1.504 ng/ml, p < 0.001). Isolated thoracic trauma and TBI lead to equally strong NSE release ad the day of admission. There is a significant linear relationship (r = 0.636, p = 0.035) between serum NSE levels and severity of pulmonary contusion at the time of admission and after 24 hours. A significant NSE release after isolated thoracic trauma peaks on the day of admission. The extent of lung contusion volume (defined as alveolar parenchymal density) correlates with NSE serum concentration. Thus, NSE has predictive value for the extent of pulmonary contusion. However, according to these data, NSE seems to have no diagnostic value as a TBI biomarker in concomitant TT.

Assessment of neuron-specific enolase, glycated haemoglobin and fasting plasma glucose levels in patients with diabetes peripheral neuropathy in Calabar Metropolis, Nigeria: A case control study

Background: Persistent hyperglycemia has been implicated in the development of neuronal complications in diabetes patients. Nerve damage and metabolic abnormalities may cause the release of neuron specific enolase into circulation. Aim: To investigate the relationship between serum neuron-specific enolase (NSE), fasting plasma glucose (FPG) and glycated haemoglobin (HbA1C) levels in diabetic patients with peripheral neuropathy. Methods: one hundred and five patients with peripheral neuropathy and 60 apparently healthy non-diabetic controls aged 45-69 years attending Clinics in General Hospital Calabar and the University of Calabar Teaching Hospital, Calabar, between July 2021 and January 2022, were recruited into the study. Fasting plasma glucose was estimated using glucose oxidase peroxidase method. Glycated haemoglobin and NSE were determined using Boronate Affinity High Performance Liquid Chromatography and ELISA methods respectively. Height and weight were measured and BMI computed, and data analyzed using Student’s t-test, ANOVA, post hoc analysis and Pearson’s correlation at P&lt;0.05. Results: Body mass index, blood pressure, fasting plasma glucose, glycated haemoglobin and neuron specific enolase concentrations were significantly different (P=&lt;0.05) between the diabetic patients and the controls. Neuron specific enolase vary significantly (P&lt;0.05) among the diabetic patients with different forms of diabetes peripheral neuropathy. Fasting plasma glucose correlated positively with NSE (r=0.441, P=0.000) and HbA1C (r=0.328, P=0.001) respectively. Glycated haemoglobin correlated positively with BMI (r=0.412, P=0.000) and NSE (r=0.328, P=0.001) in that order. Conclusion: This study has shown that glycated haemoglobin and fasting plasma glucose are related with neuron specific enolase levels in patients with diabetes peripheral neuropathy. Thus, rising levels of glycated haemoglobin and fasting plasma glucose (poor glycemic control) may be associated with progressive nerve damage in patients with diabetes peripheral neuropathy.

Negligible influence of moderate to severe hyperthermia on blood-brain barrier permeability and neuronal parenchymal integrity in healthy men.

With growing use for hyperthermia as a cardiovascular therapeutic, there is surprisingly little information regarding the acute effects it may have on the integrity of the neurovascular unit (NVU). Indeed, relying on animal data would suggest hyperthermia comparable to levels attained in thermal therapy will disrupt the blood-brain barrier (BBB) and damage the cerebral parenchymal cells. We sought to address the hypothesis that controlled passive hyperthermia is not sufficient to damage the NVU in healthy humans. Young men (n = 11) underwent acute passive heating until +2°C or absolute esophageal temperature of 39.5°C. The presence of BBB opening was determined by trans-cerebral exchange kinetics (radial-arterial and jugular venous cannulation) of S100B. Neuronal parenchymal damage was determined by the trans-cerebral exchange of tau protein, neuron-specific enolase (NSE), and neurofilament-light protein (NF-L). Cerebral blood flow to calculate exchange kinetics was measured by duplex ultrasound of the right internal carotid and left vertebral artery. Passive heating was performed via a warm-water perfused suit. In hyperthermia, there was no increase in the cerebral exchange of S100B (P = 0.327), tau protein (P = 0.626), NF-L (P = 0.447), or NSE (P = 0.908) suggesting the +2°C core temperature is not sufficient to acutely stress the NVU in healthy men. However, there was a significant condition effect (P = 0.028) of NSE, corresponding to a significant increase in arterial (P = 0.023) but not venous (P = 0.173) concentrations in hyperthermia, potentially indicating extra-cerebral release of NSE. Collectively, results from the present study support the notion that in young men there is little concern for NVU damage with acute hyperthermia of +2 °C.NEW & NOTEWORTHY The acute effects of passive whole-body hyperthermia on the integrity of the neurovascular unit (NVU) in humans have remained unclear. We demonstrate that passive heating for ∼1 h until an increase of +2°C esophageal temperature in healthy men does not increase the cerebral release of neuronal parenchymal stress biomarkers, suggesting the NVU integrity is maintained. This preliminary study indicates passive heating is safe for the brain, at least in young healthy men.

A Missing Link between Neuron Specific Enolase Release and Poor Prognosis in Aging Patients with B-cell Lymphoma.

A Missing Link between Neuron Specific Enolase Release and Poor Prognosis in Aging Patients with B-cell Lymphoma.

Quantification of Lipid Filtration and the Effects on Cerebral Injury During Cardiopulmonary Bypass

Lipid microemboli (LME) are formed in pericardial suction blood which, when returned to the cardiopulmonary bypass (CPB) circuit, can pass through filter materials and are returned to the arterial cannula. LME have been observed to enter all major organs and have been associated with small capillary arteriolar dilatations in the brains of patients who have died after CPB. However, a causal relationship showing correlation between LME and organ dysfunction has not been demonstrated, or whether removal of LME results in improved organ function. A prospective, single center, randomized controlled trial examined 30 patients (15 per group) undergoing coronary artery bypass grafting using CPB with or without a lipid-depleting filter. The effects of LME filtration on neurocognitive injury were assessed using neuron-specific enolase (NSE). The study group showed a significant reduction in LME after filtration of the pericardial suction blood (p < 0.001), whereas the control group exhibited a significant rise in LME (p < 0.001). There was a significant reduction in peak NSE release (p= 0.013) and significant attenuation throughout the postoperative period (p= 0.002). Correlation and regression analyses showed a significant relationship between the number ofLME post-CPB and peak NSE release (r= 0.42, p=0.02). Several methods of LME filtration have been proposed, but none provided a suitable, efficacious method for use within the clinical setting. The RemoweLL CPB system removes significant numbers of LME from the cardiotomy suction. Furthermore, LME correlate to the release of a known marker of neurologic injury.

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial)

BackgroundIn intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. MethodsIn a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35–45mmHg) or TTMH (PaCO2 50–55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. ResultsWe enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment.NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). ConclusionsIn CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.

The neuroprotective effect of magnesium sulphate during iatrogenically-induced ventricular fibrillation

We studied the neuroprotective effect of magnesium sulphate (MgSO4) administered before ventricular fibrillation was induced for internal cardioverter defibrillator threshold testing, and continued during reperfusion. With the intention of increasing serum magnesium (Mg) to >1.2 mmol/L, 15 patients received 16 mmol of MgSO4, IV, followed by 5 mmol over two hours. Fifteen patients received placebo. Serum neuron-specific enolase (NSE) was assessed, as well as pre- and postoperative neurocognitive function. NSE increased in all patients, reaching a peak at 24 hours. The target Mg level was maintained throughout surgery in only nine of the Mg patients, and mainly in those with low lean body mass (LBM). In these patients, increased Mg levels were related to altered NSE release (P<0.05). NSE increased when serum Mg dropped to <1.2 mmol/L, finally exceeding levels of inadequately or untreated patients. Neurocognitive function after surgery was similar between groups. Insufficient dosing could account for our results, as NSE release could be inhibited by Mg >1.2 mmol/L. For neuroprotection, the Mg dosage should be adjusted according to LBM and infusion be extended to >2 hours.

Invasive versus non-invasive cooling after in- and out-of-hospital cardiac arrest: a randomized trial

Mild induced hypothermia (MIH) is indicated for comatose survivors of sudden cardiac arrest (SCA) to improve clinical outcome. In this study, we compared the efficacy of two different cooling devices for temperature management in SCA survivors. Between April 2008 and August 2009, 80 patients after survived in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) were included in this prospective, randomized, single center study. Hypothermia was induced after randomization by either invasive Coolgard(®) cooling or non-invasive ArcticSun(®) surface cooling at 33.0 °C core body temperature for 24 h followed by active rewarming. The primary endpoint was defined as the efficacy of both cooling systems, measured by neuron-specific enolase (NSE) levels as a surrogate parameter for brain damage. Secondary efficacy endpoints were the clinical and neurological outcome, time to start of cooling and reaching the target temperature, target temperature-maintenance and hypothermia-associated complications. NSE at 72 h did not differ significantly between the 2 groups with 16.5 ng/ml, interquartile range 11.8-46.5 in surface-cooled patients versus 19.0 ng/ml, interquartile range 11.0-42.0 in invasive-cooled patients, p = 0.99. Neurological and clinical outcome was similar in both groups. Target temperature of 33.0 °C was maintained more stable in the invasive group (33.0 versus 32.7 °C, p < 0.001). Bleeding complications were more frequent with invasive cooling (n = 17 [43.6 %] versus n = 7 [17.9 %]; p = 0.03). Invasive cooling has advantages with respect to temperature management over surface cooling; however, did not result in different outcome as measured by NSE release in SCA survivors. Bleeding complications were more frequently encountered by invasive cooling.

The release of S-100B and NSE in severe traumatic head injury is associated with APOE ε4

In this article we tested the hypothesis that the level of two biochemical markers of brain injury may be associated with the apolipoprotein E (APOE) ε4 allele. In this prospective consecutive study patients with sTBI were included (n = 48). Inclusion criteria were Glasgow Coma Scale (GCS) score ≤ 8 at the time of intubation and sedation, patient age between 15 and 70 years, an initial cerebral perfusion pressure > 10 mmHg, and arrival to our level-one trauma university hospital within 24 h after trauma. Blood samples for neuron-specific enolase (NSE) and S-100B were collected as soon as possibly after arrival, and then twice daily (12-h intervals) for 5 consecutive days. Venous blood was used for APOE genotype determination. Clinical outcome at 3 months after injury was assessed with the Extended Glasgow Outcome Scale (GOSE). Significantly higher levels of the maximal S-100B (S-100B(max)) and area under the curve (S-100B(AUC)) were found in subjects with the APOE ε4 allele compared to those with non-ε4. A similar tendency was observed for NSE(max) and NSE(AUC), though not statistically significant. Our data indicate that there might be a gene-induced susceptibility to severe traumatic brain injury and that patients with the APOE ε4 allele may be more predisposed to brain cellular damage measured as S-100B and NSE. Thus, it seems to be of importance to consider the APOE genotype in interpreting the levels of the biomarkers.

Evaluation of Methods to Predict Early Long-Term Neurobehavioral Outcome After Coronary Artery Bypass Grafting

Postoperative cognitive decrease (POCD) represents the most frequent complication in modern cardiac surgery. The application of easily assessable surrogate parameters that predict long-term POCD at early time points is tempting. The aim of the present study was to analyze the predictive value of cerebral biomarkers, diffusion-weighted magnetic resonance imaging (DWI), and cognitive bedside testing after coronary artery bypass grafting (CABG). From 106 patients who underwent elective CABG, blood samples were drawn for the measurement of protein S100B and neuron-specific enolase release at baseline, at the end of surgery, and 48 hours afterward. Cerebral DWI was carried out before and 2 to 4 days after surgery. Cognitive functioning was assessed before, 2 to 4 days (bedside testing) after, and 3 months after CABG. On DWI, lesions were detected in 15.1% of patients. Biomarker levels and the presence of acute ischemic lesions on DWI were not associated with long-term POCD. Early POCD was correlated with 3-month POCD (r = 0.46, p <0.001). Ninety-one percent of patients who had shown moderate to severe POCD (<-1.5 z scores) in the early phase still had decreased memory functioning at 3 months compared to baseline (likelihood ratio 5.23). Early POCD was asserted as the only predictor for long-term POCD in a stepwise multiple linear regression model (R(2) = 0.20, p <0.001), excluding age, length of surgery, aortic clamping and cardiopulmonary bypass duration, the number of anastomoses, and postoperative neuron-specific enolase and S100B levels. In conclusion, the results show that in contrast to biomarkers, DWI, age, or intraoperative variables, early neuropsychological bedside testing predicts long-term POCD after CABG with acceptable accuracy.

Neuroplasticity and neuroprotection in enteric neurons: Role of epithelial cells

Neurons of enteric nervous system (ENS) regulate intestinal epithelial cells (IEC) functions but whether IEC can impact upon the neurochemical coding and survival of enteric neurons remain unknown. Neuro-epithelial interactions were studied using a coculture model composed of IEC lines and primary culture of rat ENS or human neuroblastoma cells (SH-SY5Y). Neurochemical coding of enteric neurons was analysed by immunohistochemistry and quantitative PCR. Neuroprotective effects of IEC were tested by measuring neuron specific enolase (NSE) release or cell permeability to 7-amino-actinomycin D (7-AAD). Following coculture with IEC, the percentage of VIP-immunoreactive (IR) neurons but not NOS-IR and VIP mRNA expression were significantly increased. IEC significantly reduced dopamine-induced NSE release and 7-AAD permeability in culture of ENS and SH-SY5Y, respectively. Finally, we showed that NGF had neuroprotective effects but reduced VIP expression in enteric neurons. In conclusion, our study identified a novel role for IEC in the regulation of enteric neuronal properties.

Serum Neuron Specific Enolase and Malondialdehyde in Patients After Out-Of-Hospital Cardiac Arrest

Sudden cardiac arrest (CA) is a leading cause of death in Europe. The victims of CA need immediate cardiopulmonary resuscitation (CPR). Patients resuscitated due to CA have high mortality rate. Prognostic evaluation based on clinical observation is uncertain and would benefit from the use of biochemical markers of hypoxic brain damage. Multiple factors of brain origin can be measured in blood. The purpose of this study was to validate the use of the serum neuron-specific enolase (NSE) and malondialdehyde (MDA) concentrations for predicting in-hospital death, after resuscitation from out-of-hospital CA. Neuronal damage and impairment of the blood-brain-barrier integrity can be detected by the release of NSE into cerebrospinal fluid and eventually into the blood. MDA represents a product of lipid peroxide decomposition reactions. In a prospective study of 35 consecutive survivors of out-of-hospital CA, serum samples were obtained within 24, 72 and 168 h after the CA. NSE and MDA concentrations were measured, relationship between concentration in group of in-hospital death and survived patients were examined. Results There was a significant difference in NSE concentration between survivors and dead group on 1st day of measurement, marginally significant difference on 3rd day and no statistically significant difference in NSE on 7th day of measurement. There was marginally significant difference in MDA levels in both groups in all days of measurements. Estimation serum concentrations of NSE but not MDA seems to be a predictor of fate of patients after CA. The exact nature of oxidative stress can only be resolved by further studies.

Herbal formula FBD extracts prevented brain injury and inflammation induced by cerebral ischemia–reperfusion

The aim of this work was to verify neuroprotective and anti-inflammatory properties of FBD, a herbal formula composed of Poria cocos, Atractylodes macrocephala and Angelica sinensis, in ICR mice subjected to repetitive 10 min of common carotid arteries occlusion followed 24 h reperfusion. Intragastrical pretreatment with supercritical carbon dioxide extract (FBD-CO 2, 37.5 mg/kg) twice daily for 3.5 d, significantly reduced Evans Blue influx, neuron specific enolase (NSE) efflux, brain infarction (all p < 0.05), also inhibited polymorphonuclear leukocytes (PMNs) infiltration ( p < 0.001), suppressed secretion of tumor necrosis factor (TNF)-α in blood ( p < 0.05), interleukin (IL)-1β and IL-8 in brain (both p < 0.01), and down-regulated cerebral expression of phosphor-IκB-α and phosphor-nuclear factor kappa-B (NF-κB), whether coupled with aqueous extract (FBD-H 2O, 150 mg/kg) or not. Moreover, FBD-CO 2 (0.1–10 μg/ml) inhibited 0.1 μM phorbol myristate acetate-evoked oxidative burst in rat PMNs, 20 ng/ml TNF-α-triggered PMNs adhesion to ECV304 endothelial cells, and PMNs neurotoxicity to PC12 neuron-like cells as well as NSE release (IC 50 1.30, 0.98, 0.24 and 0.82 μg/ml, respectively). Our study demonstrated that FBD-CO 2 prevented brain ischemia/reperfusion injury, at least in part, by limiting PMNs infiltration and neurotoxicity mediated by TNF-α, IL-1β and IL-8, via inhibition on NF-κB activation.

Neuron-specific enolase and tau protein as neurobiochemical markers of neuronal damage are related to early clinical course and long-term outcome in acute ischemic stroke

Objectives Analyses of neuron-specific enolase (NSE) and tau protein in patients with hyperacute ischemic stroke, their association with infarct volume, severity of the neurological deficit, the neurovascular status and functional outcome. Patients and methods In 66 consecutive patients, serial venous blood samples were taken at 3, 6, 12, 18, 24, 48, 72, 96, and 120 h after stroke onset. The neurovascular status was assessed by repetitive extra- and transcranial duplex sonography. Neurological deficits were quantified by the NIH stroke scale, and functional outcome was assessed with the modified Rankin scale (mRS). Results After a first rise within 3 h, NSE decreased followed by a secondary increase until Day 5. Tau protein concentrations showed a continuous increase from admission onward. NSE and tau release were highly correlated with severity of neurological deficits and infarct volume ( P = 0.001). NSE, but not tau protein, release was associated to the neurovascular status on admission. NSE and tau protein values were significantly correlated with the functional outcome at 3 months ( P < 0.001). Conclusion Release kinetics of NSE and tau protein are associated with patients’ clinical deficits and infarct volume, and may be used as an additional predictor of the early course and functional outcome.

Clinical value of neuron specific enolase in small cell lung cancer

Lung cancers are fast growing tumors with early metastatic spread and poor prognosis. Most primary lung tumors can be classified into four mayor histological types: squamous cell carcinoma, adenocarcinoma, large cell carcinoma and small cell lung cancer (SCLC). SCLC differs clinically and biologically from the other three histological types, which are all generally referred to as non small cell lung cancer (NSCLC). Thus, both SCLC and NSCLC represent heterogeneous groups. Enolase (2 phospho-D glycerate hydrolase, EC 4.2.1.11) exist as several dimeric isoenzymes (aa, ab, ag, bb, gg). The ag and gg enolase isoenzymes are also known as neuron specific enolase (NSE). They are produced in central and peripheral neurons and malignant tumors (SCLC, neuroblastomas, intestinal carcinoid). NSE is the leading tumor marker in SCLC. Release of NSE in serum in patients where histological evidence is absent may support a diagnosis of SCLC. NSE should not be used for screening purposes. NSE does not correlate with the localization of metastases and/or with brain metastases, although it correlates well with the clinical stage. High NSE concentrations reflect advanced tumor stage and suggest a bad prognosis. In patients with SCLC serum levels of NSE reflect the response to chemotherapy. Increasing tumor marker indicate progressive disease often before this is evident from imaging techniques. Measurement of NSE may be helpful; guideline recommendations for their proper use in differential diagnosis and in monitoring the efficacy of therapy have been proposed by EGTM.

The extent of damage following repeated injury to cultured hippocampal cells is dependent on the severity of insult and inter-injury interval

Recent evidence suggests repeated mild brain trauma may result in cumulative damage. We investigated cell damage and death in hippocampal cultures following repeated mechanical trauma in vitro by measuring propidium iodide (PrI) uptake, release of neuron-specific enolase (NSE) and glial S-100beta protein, and performing neuronal counts. Cultures receiving two mild injuries (31% stretch) 1 or 24 h apart displayed different profiles of PrI uptake and S-100beta release, although neuronal loss and NSE release was similar in both paradigms. Cells receiving a subthreshold, low-level stretch (10%) repeated several times eventually stained with PrI. Cultures administered 10% stretch before mild injury released less S-100beta than mild injury alone, suggesting a preconditioning effect. Lastly, exogenous S-100beta applied to injured cultures decreased PrI uptake, implying a protective role. These results suggest cumulative damage is dependent on injury severity and inter-injury interval, and that neurons and glia react differently to various injury paradigms.

Release of neurobiochemical markers of brain damage is related to the neurovascular status on admission and the site of arterial occlusion in acute ischemic stroke

Objectives The study aimed at an analysis of the kinetics of protein S100B and neuron-specific enolase (NSE) and their relation to the site of arterial occlusion in patients with acute ischemic stroke. Methods We investigated 32 consecutive patients admitted within 6 h after stroke onset. Serial venous blood samples were taken hourly between 1 and 6 h, and at 12, 18, 24, 48, 72, 96, and 120 h after stroke onset. The neurovascular status was assessed on admission and monitored by repetitive extracranial and transcranial duplex sonography. In all patients, infarct volume was calculated. The neurological deficit was quantified by the National Institutes of Health stroke scale score, and functional outcome after 3 months was assessed with the modified Rankin Scale. Results Patients with normal flow velocities in basal cerebral arteries at admission showed significantly less S100B release than those with main stem or multiple branch occlusions ( p<0.01). S100B cut-off values of 0.15 μg/l (between 6 and 18 h), 0.21 μg/l (between 24 and 48 h) and 0.5 μg/l (from 72 to 120 h) differentiated best between patients with initially normal and pathological sonographic vessel findings. The release of S100B and NSE was highly correlated with the severity of the corresponding neurological deficit as well as with the final infarct volume. S100B concentrations from 6 h on were associated with the functional outcome. S100B values 48 h after stroke above 0.2 μg/l indicated a poor functional status 3 months after stroke. Conclusions Protein S100B may serve as a monitoring parameter in acute ischemic stroke, especially with respect to the neurovascular status. Furthermore, S100B obtains additional information about functional outcome.

Release of Neuron-Specific Enolase and S100 After Implantation of Cardioverters/Defibrillators

Pelinka, Linda E. MD; Schmid-hammer, Robert MD; Redl, Heinz PhD; Bahrami, Soheyl PhD Author Information

Cell death, glial protein alterations and elevated S-100β release in cerebellar cell cultures following mechanically induced trauma

Recent studies in vivo have shown that cells of the cerebellum, and particularly Purkinje neurons (PNs), are susceptible to damage following traumatic brain injury (TBI). To investigate more closely the effects of TBI at the cellular level, we subjected cerebellar cell cultures to injury using an in vitro model of stretch-induced mechanical trauma and found increased cell damage and neuronal loss with increasing levels of injury and time post-injury. The release of neuron-specific enolase and S-100β were also elevated after injury. Compared to our previous findings in hippocampal cells, S-100β levels were much higher in cerebellar cultures after injury, suggesting that cells from different brain regions show variable responses to mechanical trauma. Lastly, the addition of exogenous S-100β to uninjured cerebellar cells caused no overt change in cell viability or overall neuronal number; there were, however, fewer calbindin-positive PNs, similar to findings after stretch injury.

Release of neuron-specific enolase and S100 after implantation of cardioverters/defibrillators.

Repeated induction of ventricular fibrillation with ensuing alterations in electroencephalogram and jugular venous oxygen saturation is common practice during insertion of transvenous implantable cardioverters/defibrillators. We investigated whether these functional changes are also associated with cerebral injury. Prospective study. University hospital. We studied 45 patients undergoing implantable cardioverter/defibrillator insertion. Eleven patients with cardiac pacemaker implantation, which was performed in the same manner yet without the necessity to induce ventricular fibrillation, served as controls. Serum neuron-specific enolase and S100 were determined before, immediately postoperatively, and 2 hrs postoperatively. In a randomly composed subgroup, neuron-specific enolase was also determined 6 and 24 hrs after surgery. Implantable cardioverter/defibrillator patients only showed an increase of both markers postoperatively. Median neuron-specific enolase values climbed from a preoperative 9.9 to 12.3 and 14.4 microg/L at 2 and 24 hrs after surgery, respectively. This increase was associated with the number of shocks and the cumulative time in circulatory arrest. The highest median S100 level (0.075 microg/L) was reached 2 hrs after the procedure. Neuron-specific enolase and S100 were extremely elevated (13.7 and 0.970 microg/L, respectively) in one patient after an extended episode of ventricular fibrillation. Plasma hemoglobin levels were in the normal range in implantable cardioverter/defibrillator patients throughout the observation period. Apparently, even brief successive periods of global cerebral ischemia cause neuronal damage without obvious severe neurologic deficits. However, they may be related to subtle postoperative neurologic or cognitive dysfunctions that a number of implantable cardioverter/defibrillator patients exhibit after implantation.