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Brain-derived neurotrophic factor (BDNF) appears to be both regulated by and a regulator of epileptogenesis. In the flurothyl (HFE) model of kindling mice exposed to successive flurothyl trials over 8 days express a rapid, long-lasting reduction in generalized seizure threshold and a more slowly evolving change in seizure phenotype in response to subsequent flurothyl exposure. The BDNF genotype of particular mouse strains appears to influence the epileptogenic progression in this model. Thus, we hypothesized that BDNF signaling pathways are altered by flurothyl-induced seizures. Following HFE kindling, fully kindled (eight seizures) adult male C57BI/6J mice had significantly elevated whole brain BDNF levels through at least 28 days after their final seizure. Mice that received only four HFE seizures (not kindled) had elevated BDNF levels, but only at 1 day post-seizure (DPSz), while BDNF levels were not significantly altered in mice receiving just one HFE seizure at any time point studied. Regional expression patterns of BDNF in the hippocampus, hypothalamus, and frontal cortex were also elevated by one DPSz and returned to control values by 14 DPSz in mice that received four HFE seizures. No changes were seen in the cerebellum, striatum, or piriform cortex. In contrast, fully kindled mice had significantly elevated BDNF levels within the hippocampus, hypothalamus, neocortex, and striatum that remained elevated through at least 14 DPSz, while levels were unchanged in the cerebellum and piriform cortex. Regional results were confirmed using anti-BDNF immunohistochemistry (IHC). Despite changes in BDNF levels following HFE kindling, we were unable to demonstrate alterations either in full-length tyrosine kinase receptor B (TrkB) expression (Western blot and IHC) or in truncated TrkB (IHC) expression levels. Together, these data suggest a model of a positive feedback loop involving seizure activity and seizure number and persistently modified BDNF signaling pathways that influences seizure phenotypes within the HFE kindling paradigm. Thus, long-term elevations in BDNF may be responsible in part for epileptogenic processes and the development of human refractory epilepsies. [Copyright &y& Elsevier]

The receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory processes. The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is dictated by the accumulation of advanced glycation end-products (AGEs) at pathologic states leading to sustained RAGE upregulation. The involvement of RAGE and its ligands in numerous pathologies and diseases makes RAGE an interesting target for therapy focused on the modulation of both RAGE expression or activation and the production or exogenous administration of AGEs. Despite the known role that the RAGE/AGE axis plays in multiple disease states, there remains an urgent need to develop noninvasive, molecular imaging approaches that can accurately quantify RAGE levels in vivo that will aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing., (© 2023 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

Aims: To investigate the role of vitamin D2 on the resolution of ST-segment elevation (STE) after a primary percutaneous coronary intervention (PCI), as serum levels of vitamin D have been associated with the severity of coronary artery disease., Methods and Results: All patients who underwent PCI for STEMI were screened for enrolment. Vitamin D2 levels were measured on admission along with other biochemical and haematologic assays. The electrocardiography (ECG) was recorded upon arrival and 60 min after the completion of PCI. The primary endpoint of the study was a ≥ 50% resolution of ST-segment amplitude (+STR) when compared to the initial ECG. A logistic regression multivariate analysis was performed to examine the association of STR with all confounding variables, including the admission levels of vitamin D. Receiver-operator characteristics analysis was used to determine the cut-off value of vitamin D that was predictive of STR. Although there was no difference in STR based on standard classification of vitamin D sufficiency, critically low levels of vitamin D (<7.5 ng/mL) were significantly associated with the absence of STR after PCI (AUC was 0.65 ± 0.07; p  < 0.001). Critical vitamin D deficiency was a moderate predictor of STR in these patients, with a sensitivity of 86% and specificity of 54%., Conclusion: We concluded that although levels below ten ng/mL were generally accepted as vitamin D deficiency, only critically low levels of this vitamin (<7.5 ng/dL) reliably predicted the resolution of ST-segment after a primary PCI for patients with STEMI.