Role of neuron-specific enolase, glial fibrillar acidic protein and NR2-antibodies in early diagnostic of ischemic stroke

Background. Application of a biomarker panel during the acute period of the ischemic stroke (IS) can contribute to a more accurate and prompter diagnostics and verification of the optimal approach to a patients’ management.Objective. We aimed to clarify values of neuron-specific enolase (NSE), glial fibrillar acidic protein (GFAP) and antibodies for NMDA receptor’s NR2-subunit (NR2-antibodies) in the acute period of IS, to compare with such values in patients without IS, to assess their relationship with severity of neurological deficit and short-term outcome and also to establish sensitivity and specificity of the biomarker panel.Design and methods. 63 patients with IS and 31 people (11 with chronic brain ischemia and 20 healthy individuals) as controls were included. Results. NSE and GFAP values in IS group exceeded reference values at the onset of disease, lowering significally by 10-14 day, while NR2-antibodies’ values were lower at the onset of the disease compared with controls, rising by 10-14 day. In patients with unfavourable short-term outcome higher levels of NSE, GFAP and NR2-antibodies were found. A panel of such biomarkers has higher sensitivity and specificity than each of them individually.Conclusion. Researched substances can be used in a biomarker panel for IS diagnostics, brain damage monitoring, patient’s condition evaluation and short outcome prognosing.

GFAP as a biomarker in frontotemporal dementia and primary psychiatric disorders: diagnostic and prognostic performance

BackgroundFrontotemporal lobar degeneration (FTLD) and primary psychiatric disorders (PPD) are characterised by overlapping clinical features but different aetiologies. Here, we assessed for the first time the potential of blood glial fibrillar acidic protein (GFAP), marker of astrogliosis, as a discriminative and prognostic tool in FTLD and PPD.MethodsThe levels of GFAP in serum (sGFAP) of patients with FTLD (N=107) and PPD (N=44) and GFAP in whole blood samples (bGFAP) from FTLD (N=10), PPD (N=10) and healthy controls (N=18) were measured. We evaluated whether the sGFAP levels associate with C9orf72 repeat expansion, survival of FTLD and PPD patients, and brain atrophy assessed cross-sectionally and longitudinally by structural T1W MRI. We also examined the correlation between sGFAP and bGFAP levels in a subset of patients.ResultssGFAP and bGFAP levels were elevated in the FTLD group compared with the PPD or control groups. Receiver operating characteristic analysis indicated an excellent diagnostic performance between FTLD and PPD (the area under the curve (AUC)=0.820, 95% CI 0.745 to 0.896). sGFAP and bGFAP levels showed a strong correlation and elevated sGFAP levels significantly associated with atrophy rate in the temporal cortex and predicted shorter survival time in patients with FTLD. No association with C9orf72 repeat expansion was detected.ConclusionssGFAP enabled differentiation of patients with FTLD and PPD and associated with shorter survival and more severe brain atrophy rate in patients with FTLD. These results suggest that blood-based GFAP represents a minimally invasive and useful biomarker in the differential diagnostics between patients with FTLD and PPD and in evaluating disease progression and astrogliosis in FTLD.

Discriminative value of glial fibrillar acidic protein (GFAP) as a diagnostic tool in acute stroke. Individual patient data meta-analysis

Glial fibrillar acidic protein (GFAP) in serum has been evaluated as a promising biomarker to differentiate between intracerebral hemorrhage (ICH) and acute ischemic stroke (AIS). We assessed its value as diagnostic and prognostic tool for ICH through a literature systematic review and individual patient data (IPD) meta-analysis.We performed a systematic search in PubMed database until November 2018 for publications that evaluated GFAP to differentiate AIS and ICH within 4.5 hours after symptoms onset. Thereafter, we invited authors of selected studies to participate in this work by providing IPD from their cohorts. We used standardized individual subject’s data to evaluate the association of GFAP concentrations with stroke subtype, demographics, stroke characteristics and factors related with GFAP measurement.From 4 selected studies, we collected data of 340 patients (236 AIS and 104 ICH). Standardized GFAP blood levels were significantly elevated in ICH compared with those with AIS (median and IQR: 0.84 (0.781–1.24), 0.79 (0.74–0.81); p<0.0001). In both stroke types, GFAP concentrations correlated with baseline stroke severity (r=0.27, p<0.0001; r=0.36, p<0.001; for AIS and ICH, respectively) but no correlation was found regarding time to sampling. Limited data precluded the evaluation of GFAP levels and functional outcome.These findings demonstrate substantially different levels of GFAP in the blood of patients with ICH compared with patients with AIS soon after the event, while no association was found with outcome. In summary, GFAP could be a valuable diagnostic tool to assist in medical decision-making and to optimize management of stroke in the acute setting.

Reactive astrogliosis in rats with LPS-induced Parkinson's disease

The astrogliosis was considered as a beneficial process to protect neurons and repair the tissue after CNS insult for a long time. However, numerous study indicate that under some specific conditions, reactive astrocytes can exacerbate neuroinflammation and tissue damage. Parkinson's disease (PD) is one of the most common neurodegenerative diseases that is a major medical and social problem. The progressive course of the disease requires continuous therapy, in the later stages it causes a disability of the patient, which entails the need for constant care and causes significant economic losses. The pathophysiological bases of CP remain unclear, making it impossible to diagnose the disease early, predict its course, and develop pathogenetic treatments. Neuroinflammation of polyetiological genesis, whose development involves micro- and astroglial cells, is considered to be a leading pathogenetic factor of CP. However, the functional state of astroglia in the conditions of development of this neuropathology remains the least studied. The aim of the study was to investigate the functional state of astroglia in rats with PD induced by bacterial lipopolysaccharide (LPS-PD). It has been established that the development of LPS-PD in rats is accompanied by reactive astrogliosis with overexpression of glial fibrillar acidic protein (GFAP) and products of its degradation by astrocytes of the hippocampal region of the brain. Overexpression of GFAP is associated with an increase in the level of myelin basic protein (MBP) in brain homogenates and a decrease in the level of neuronal NO synthase.

MARKERS OF DAMAGE TO NERVOUS TISSUE IN LIQUOR PATIENTS WITH VARIOUS FORMS OF NEUROSYPHILIS

The purpose: to study the features of markers of lesion of nervous tissue and cytokines in patients with various forms of neurosyphilis. Material and methods. The complex clinical examination of patients with syphilis was carried out in the venereological department of the Clinical dermatovenerologic dispensary in Omsk in the period from 2015 to 2017, in order to identify signs of damage to the nervous system. Results: the presence of regularities and features in the deviation of the immune status in neurosyphilis was found. Conclusion. Analysis of the immunological changes in the cerebrospinal fluid showed that the level of interleukin 12p40 is significantly higher in the cerebrospinal fluid of patients with neurosyphilis, while the maximum values of these indicators are in patients with manifest forms of pathology. In patients with neurosyphilis, the concentration of glial fibrillar acidic protein in CSF was statistically significantly increased then in comparison group.

Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients

ObjectiveTo report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies.MethodsFrom January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients’ serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot. GFAP autoantibodies were detected by immunohistochemistry and their specificity confirmed by CBA using cells expressing human GFAPα and GFAPδ proteins, by immunoblot and immunohistochemistry on GFAP-/- mouse brain sections.ResultsSerum and/or CSF IgG of 22/451 (5%) patients bound to human GFAP, of which 22/22 bound to GFAPα, 14/22 to both GFAPα and GFAPδ and none to the GFAPδ isoform only. The neurological presentation was: meningoencephalomyelitis or encephalitis in 10, movement disorder (choreoathetosis or myoclonus) in 3, anti-epileptic drugs (AED)-resistant epilepsy in 3, cerebellar ataxia in 3, myelitis in 2, optic neuritis in 1 patient. Coexisting neural autoantibodies were detected in five patients. Six patients had other autoimmune diseases. Tumours were found in 3/22 patients (breast carcinoma, 1; ovarian carcinoma, 1; thymoma, 1). Nineteen patients were treated with immunotherapy and 16 patients (84%) improved. Histopathology analysis of the leptomeningeal biopsy specimen from one patient revealed a mononuclear infiltrate with macrophages and CD8+ T cells.ConclusionsGFAP autoimmunity is not rare. The clinical spectrum encompasses meningoencephalitis, myelitis, movement disorders, epilepsy and cerebellar ataxia. Coexisting neurological and systemic autoimmunity are relatively common. Immunotherapy is beneficial in most cases.

Neurotrophic factors concentration in rat brain at the experimental coma

Aim. To study the changes of neurotrophic factors concentrations depending on stage of intoxication with deprivation substances (ethanol or sodium oxybutirate) in rats. Methods. Experiments were performed on male white laboratory rats. Control and experimental groups included 10 animals each. Half-lethal doses of a deprivation substance (ethanol or sodium oxybutirate) were introduced intraperitoneally 3, 6, 12, 24 and 72 hours before blood specimen collection. Neuron-specific enolase, S-100 protein, brain-derived neurotrophic factor, pigment epithelium-derived factor, glial fibrillary acidic protein serum levels were measured by enzyme immunoassay. Results. At single infusion of mean lethal dose of sodium oxybutyrate S-100 protein serum level significantly increased after 6 hours compared to control and stayed elevated during the first 24 hours. The levels of neurotrophic and neuroprotective factors also significantly increased 3 and 6 hours after the drug administration. The toxic dose of ethanol have significantly increased (over than 1.8 times compared to the controls) the concentration of protein S-100 in rats after 3 hours. The maximum increase in the protein S-100 level (by 2.6 times and over) was noted 12 hours after the toxicant administration. Glial fibrillar acidic protein concentration was 2.9 times higher compared to controls 3 hours after and 1.9 times higher 6 hours after higher the ethanol administration (р 0.05). The concentration of brain - derived neurotrophic factor has also increased from 3 to 12 hours after the toxicant administration, and was 2.1 to 2.4 times higher compared to intact animals. Conclusion. Studying of neurotrophic factors brain in plasma showed that the development of hypoxia, accompanying coma, leads to higher serum levels of S-100 protein, brain-derived neurotrophic factor and glial fibrillar acidic protein. The increase in the concentration of S-100 is a marker for the presence of brain damage. The observed increase of glial fibrillar acidic protein in experiments with ethanol may indicate its more severe brain tissue damage compared to sodium oxybutyrate.