Expression of stromal‐cell‐derived factor‐1 (SDF‐1): a predictor of ischaemic stroke?

Background and purpose: Platelet stromal‐cell‐derived factor‐1 (SDF‐1) plays a pivotal role in angiogenesis and the regeneration of ischaemic tissue through the regulation of haematopoietic progenitor cells and is upregulated at the sites of vascular injury and platelet activation. Thus, SDF‐1 has recently been discussed as a predictor in ischaemic diseases such as acute myocardial infarction. However, no clinical data pertinent to the investigation of the platelet SDF‐1 expression in patients with stroke are available. Methods: We consecutively evaluated 196 patients who were admitted to the stroke unit with symptoms suspected for stroke. Surface expression of the platelet activation markers (P‐selectin and GPIb) and the expression of platelet‐bound SDF‐1 were determined by two‐colour whole blood flow cytometry. Results: Patients with transient ischaemic attack (TIA) as well as with ischaemic stroke showed similar levels of SDF‐1 expression on hospital admission compared with patients with non‐ischaemic (NI) events and with 30 healthy controls (TIA (mean fluorescence intensity ± SD): 31.5 ± 18.2 vs. NI: 26.4 ± 15.7; P = 0.361; stroke: 28.7 ± 19.8 vs. NI; P = 0.943; control: 26.1 ± 11.3; P > 0.05 compared with all). Platelet SDF‐1 expression showed a trend with the severity of stroke according to National Institute of Health Stroke Scale score (r = 0.125; P = 0.085), but significantly correlated with the peak levels of C‐reactive protein (r = 0.218; P = 0.002) and with the levels of platelet activation (P‐selectin: r = 0.389; P = 0.001). Multifactorial analysis of covariance revealed a significant influence on platelet SDF‐1 expression by smoking (P = 0.019). Conclusions: Platelet SDF‐1 surface expression did not show any significant difference in patients with TIA and ischaemic stroke compared with patients with NI events. Thus, single biomarker evaluation of platelet SDF‐1 surface expression is not helpful to predict ischaemic stroke.     

Does early treatment improve outcomes in N‐methyl‐d‐aspartate receptor encephalitis?

N‐methyl‐d ‐aspartate (NMDA) receptor encephalitis is a treatable cause of autoimmune encephalitis in both children and adults. It is still unclear if the natural history of the condition in children is altered by early treatment with immunosuppressive therapy. We looked at the outcomes of five children (two males, three females; mean age 6y 9mo, range 4–8y) who were treated empirically for autoimmune encephalitis within a brief period of presentation. Features that led clinicians to suspect autoimmune encephalitis included prominent neuropsychiatric features, movement disorder, seizures, and dysautonomic features. Immunosuppressive therapy was carried out in all cases. In this series of children, in whom the median time from symptom onset to treatment was 5 days and median length of time for follow‐up was 24 months, four out of the five (80%) recovered to their baseline. Early initiation of immunosuppressive therapy may result in improved clinical outcomes.     

Abstinence from cocaine‐self‐administration activates the nELAV/GAP ‐43 pathway in the hippocampus: A stress‐related effect?

We previously demonstrated that nELAV/GAP‐43 pathway is pivotal for learning and its hippocampal expression is up‐regulated by acute stress following repeated cocaine administration. We therefore hypothesized that abstinence‐induced stress may sustain nELAV/GAP‐43 pathway during early abstinence following 2 weeks of cocaine self‐administration. We found that contingent, but not non‐contingent, cocaine exposure selectively increases hippocampal nELAV, but not GAP‐43, expression immediately after the last self‐administration session, an effect that wanes after 24 h and that comes back 7 days later when nELAV activation becomes associated with increased expression of GAP‐43, an effect again observed only in animals self‐administering the psychostimulant. Such effect is specific for nELAV since the ubiquitous ELAV/HuR is unchanged. This nELAV profile suggests that its initial transient alteration is perhaps related to the daily administration of cocaine, while the increase in the nELAV/GAP‐43 pathway following a week of abstinence may reflect the activation of this cascade as a target of stressful conditions associated with drug‐related memories. © 2016 Wiley Periodicals, Inc.     

Worldwide access to evidence‐based mental health literature: How useful is PubMed in Anglo‐Saxon and non‐Anglo‐Saxon countries?

The aim of this study was to verify the presence of cultural variety among the psychiatric journals available on PubMed, the major online tool for accessing literature. Data for analysis were taken from a survey of the world psychiatric journals indexed in Index Medicus 1999 (IM), the alphabetical list used by PubMed, and from the mean impact factor (IF) values of the journals. Approximately 80% of international psychiatric literature available on PubMed is published in Anglo-Saxon countries, especially in the USA (59.8% of the total). The widespread use of the English language (94.9% of all the journals) further stresses the dominance of the Anglo-Saxon cultural model, as do the mean IF values of Anglo-Saxon journals compared to non-Anglo-Saxon publications (3.252 vs. 1.693; P=0.0079). The under-representation of non-Anglo-Saxon cultural models on PubMed plays a negative role for bringing about a truly multicultural literature in psychiatry.     

Rostrolateral prefrontal cortex: Domain‐general or domain‐sensitive?

The ability to jointly consider several structured mental representations, or relations, is fundamental to human cognition. Prior studies have consistently linked this capacity for relational integration to rostrolateral prefrontal cortex (RLPFC). Here, we sought to test two competing hypotheses: (1) RLPFC processes relations in a domain-general manner, interacting with different brain regions as a function of the type of lower-level relations that must be integrated; or (2) A dorsal-ventral gradient exists within RLPFC, such that relational integration in the visuospatial domain involves relatively more dorsal RLPFC than integration in the semantic domain. To this end, we examined patterns of fMRI activation and functional connectivity during performance of visuospatial and semantic variants of a relational matching task. Across the two task variants, the regions that were most strongly engaged during relational comparison were left RLPFC and left intraparietal sulcus (IPS). Within left RLPFC, there was considerable overlap in activation for the semantic and visuospatial tasks. However, visuospatial task activation peaks were located dorsally to the semantic task peaks. In addition, RLPFC exhibited differential functional connectivity on the two tasks, interacting with different brain regions as a function of the type of relations being compared. While neurons throughout RLPFC may share the function of integrating diverse inputs, individual RLPFC neurons may have privileged access to particular representations depending on their anatomical inputs, organized along a dorsal-ventral gradient. Thus, RLPFC is well-positioned as a locus of abstraction from concrete, domain-specific details to the general principles and rules that enable higher-level cognition.     

Activity‐dependent Wnt 7 dendritic targeting in hippocampal neurons: Plasticity‐ and tagging‐related retrograde signaling mechanism?

Wnt proteins have emerged as transmembrane signaling molecules that regulate learning and memory as well as synaptic plasticity at central synapses (Inestrosa and Arenas (2010) Nat Rev Neurosci 11:77‐86; Maguschak and Ressler (2011) J Neurosci 31:13057‐13067; Tabatadze et al. (2012) Hippocampus 22: 1228‐1241; Fortress et al. (2013) J Neurosci 33:12619‐12626). For example, there is both a training‐selective and Wnt isoform‐specific increase in Wnt 7 levels in hippocampus seven days after spatial learning in rats (Tabatadze et al. (2012) Hippocampus 22: 1228‐1241). Despite growing interest in Wnt signaling pathways in the adult brain, intracellular distribution and release of Wnt molecules from synaptic compartments as well as their influence on synaptic strength and connectivity remain less well understood. As a first step in such an analysis, we show here that Wnt 7 levels in primary hippocampal cells are elevated by potassium or glutamate activation in a time‐dependent manner. Subsequent Wnt 7 elevation in dendrites suggests selective somato‐dendritic trafficking followed by transport from dendrites to their spines. Wnt 7 elevation is also TTX‐reversible, establishing that its elevation is indeed an activity‐dependent process. A second stimulation given 6 h after the first significantly reduces Wnt 7 levels in dendrites 3 h later as compared to non‐stimulated controls suggesting activity‐dependent Wnt 7 release from dendrites and spines. In a related experiment designed to mimic the release of Wnt 7, exogenous recombinant Wnt 7 increased the number of active zones in presynaptic terminals as indexed by bassoon. This suggests the formation of new presynaptic release sites and/or presynaptic terminals. Wnt signaling inhibitor sFRP‐1 completely blocked this Wnt 7‐induced elevation of bassoon cluster number and cluster area. We suggest that Wnt 7 is a plasticity‐related protein involved in the regulation of presynaptic plasticity via a retrograde signaling mechanism as previously proposed (Routtenberg (1999) Trends in Neuroscience 22:255‐256). These findings provide support for this proposal, which offers a new perspective on the synaptic tagging mechanism (Redondo and Morris (2011) Nat Rev Neurosci 12:17‐30). © 2013 Wiley Periodicals, Inc.     

HMGB‐1, TLR4, IL‐1R1, TNF‐α, and IL‐1β: novel epilepsy markers?

Aim: The purpose of this study was to compare HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels in patients with mild and severe epilepsy with those in a healthy control group. Methods: Children aged 4–17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB‐1, TLR4, IL‐1R1, TNF‐α and IL‐1β levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. Results: HMGB‐1, TLR4, TNF‐α, and IL‐1β levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL‐1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). Conclusion: In this first report to identity a possible correlation between HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug‐refractory epilepsy.