The blood-brain barrier (BBB) disruption is a critical step in paraneoplastic neurological syndrome (PNS) development. Several cytokines have been implicated in BBB breakdown. However, the exact step-by-step mechanism in which PNS develops is unknown, and the relationship between a systemic neoplasm and BBB is multilevel. The aim of the present study was to examine serum markers of BBB breakdown (S100B protein, neuron-specific enolase, NSE) and concentrations of proinflammatory (TNF-alpha, VEGF) and anti-inflammatory/immunosuppressive cytokines (IL-4), and to establish their interrelationship in patients with PNS. We analyzed 84 patients seropositive for onconeural antibodies that originated from a cohort of 250 cases with suspected PNS. Onconeural antibodies were estimated with indirect immunofluorescence and confirmed with Western blotting. Serum S-100B was estimated using electrochemiluminescence immunoassay. NSE, VEGF, TNF-alpha and IL-4 were analyzed with ELISA. We found that S-100B protein and NSE serum concentrations were elevated in PNS patients without diagnosed malignancy, and S-100B additionally in patients with peripheral nervous system manifestation of PNS. Serum VEGF levels showed several abnormalities, including a decrease in anti-Hu positive patients and increase in PNS patients with typical manifestation and/or central nervous system involvement. Increase in TNF-alpha was observed in patients with undetermined antibodies. To conclude, the presence of paraneoplastic neurological syndrome in seropositive patients does not affect serum markers of BBB breakdown, with the exception of the group without clinically demonstrated malignancy and patients with peripheral manifestation of PNS. S-100B and NSE might increase during early phase of PNS. VEGF may be involved in typical PNS pathophysiology.
To evaluate the significance of circulating tight-junction (TJ) proteins as predictors of hemorrhagic transformation (HT) in ischemic stroke patients.We examined 458 consecutive ischemic stroke patients, 7.2% of whom had clinically evident HT. None of the patients was treated with thrombolytic drugs. Serum levels of standard markers of blood-brain barrier (BBB) breakdown (S100B, neuron-specific enolase), TJ proteins (occludin [OCLN], claudin 5 [CLDN5], zonula occludens 1 [ZO1]), and molecules involved in BBB disintegration (matrix metalloproteinase 9 and vascular endothelial growth factor [VEGF]) were assessed upon admission to the emergency department. A clinical deterioration caused by HT (cdHT) was defined as an increase of ≥4 points in the NIH Stroke Scale score in combination with a visible HT on a CT scan performed immediately after the onset of new neurologic symptoms.Patients with cdHT had higher concentrations of OCLN, S100B, and the CLDN5/ZO1 ratio, and a lower level of VEGF than those without cdHT. CLDN5 levels also correlated with cdHT occurrence when estimated within 3 hours of stroke onset. We also demonstrated correlations between the levels of circulating TJ molecules and the level of S100B, which is a previously established marker of BBB disruption.Analyzing serum levels of TJ proteins, like CLDN5, OCLN, and CLDN5/ZO1 ratio, as well as S100B and VEGF, is an effective way to screen for clinical deterioration caused by HT in ischemic stroke patients, both within and after the IV thrombolysis time window.
The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs). The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10−4), IDH1/2 mutation (P < 10−4), chromosome 4 loss (P < 10−3), and better overall survival (P < 10−4). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023). The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.
The paper presents the concept of the system for the analysis of the effect of neurochemical processes on activity and structure of biologically realistic neural networks. Detailed are the neurological-based motivation for the work, the overall structure of the system and selected, implemented modules. The paper presents the current state of the system's implementation and the future work
Summary The study was aimed at the evaluation of blood platelet activation and reactivity in patients in the convalescent phase of stroke (n=58) and controls matched in respect to risk factors of vascular pathology (n=55). Both groups were treated daily with acetylsalicylic acid (ASA), 150 mg/day. Using flow cytometry, the expressions of P-selectin and the active GP IIb/IIIa receptor, as well as the fraction of platelet-derived microparticles (PMPs) and total platelet aggregates (Ag), were evaluated in non-stimulated platelets and in platelets stimulated in vitro by thrombin, thrombin receptor activating peptide (TRAP) or ADP. The expression of P-selectin in non-stimulated platelets was found to be significantly (p=0.04) lower in stroke patients. In parallel, these patients manifested a significantly (p=0.0008) higher proportion of PMPs and a lowered (p=0.003) proportion of Ag, as compared to the controls. In the stroke patients the increased expressions of P-selectin and active GP IIb/IIIa in TRAP- or ADP-activated cells were less pronounced (p<0.01), while the increments in PMP fraction remained higher (p<0.05). Our results may indicate that chronic platelet activation develops in patients in the convalescent phase of stroke and the process of PMP generation prevails over blood platelet degranulation and aggregation. This shift may be particularly unfavourable due to the procoagulative and proatherosclerotic properties of PMPs, accompanied by their decreased sensitivity to the action of antiplatelet drugs. Note: The results of this study were presented in part during a poster session at the XVIII European Stroke Conference in Stockholm, 26–29 May 2009.
