Brain research
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Interleukin-1 beta (IL-1β) is one of pro-inflammatory cytokines. Recent studies have shown that IL-1β impairs hippocampal neurogenesis, mediates proliferation and differentiation of multipotent neural precursor cells (NPCs), and exerts effects of anti-proliferation, anti-neurogenesis, and pro-gliogenesis on embryonic hippocampal NPCs. The aim of this study was to examine the effect of IL-1β on the differentiation of hippocampal NPCs into functional serotonergic neurons, which play important roles in the pathophysiology and treatment of depression. ⋯ After three passages and phenotyping, hippocampal NPCs were cultured in a differentiating medium with various concentrations (5, 10, and 20 ng/mL) of IL-1β for 7 days. At the endpoint, the serotonergic differentiation of hippocampal NPCs in IL-1β-treated cultures decreased in a dose-dependent manner and this effect was blocked by IL-1ra, an IL-1 receptor antagonist capable of blocking the effects of IL-1 by binding to the same receptor (IL-1R1) without triggering signaling; serotonin in the lysate of the differentiated hippocampal NPCs decreased in IL-1β-treated cultures; and levels of Bcl-2 and phosphorylated extracellular-regulated kinase (pERK) were also lower in differentiated hippocampal NPCs with IL-1β treatment. These results support the hypothesis that IL-1β is an important factor in the stress-associated neuropathology and psychopathology and has relevance to the treatment of depressive symptoms in patients with depression.
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The present study examines the brain-level representation and composition of meaning in scalar quantifiers (e.g., some), which have both a semantic meaning (at least one) and a pragmatic meaning (not all). We adopted a picture-sentence verification design to examine event-related potential (ERP) effects of reading infelicitous quantifiers for which the semantic meaning was correct with respect to the context but the pragmatic meaning was not, compared to quantifiers for which the semantic meaning was inconsistent with the context and no additional pragmatic meaning is available. In the first experiment, only pragmatically inconsistent quantifiers, not semantically inconsistent quantifiers, elicited a sustained posterior negative component. ⋯ We hypothesize that the sustained negativity reflects cancellation of the pragmatic inference and retrieval of the semantic meaning. In our second experiment, we found that the process of re-interpreting the quantifier was independent from lexico-semantic processing: the N400 elicited by lexico-semantic violations was not modulated by the presence of a pragmatic inconsistency. These findings suggest that inferential pragmatic aspects of meaning are processed using different mechanisms than lexical or combinatorial semantic aspects of meaning, that inferential pragmatic meaning can be realized rapidly, and that the computation of meaning involves continuous negotiation between different aspects of meaning.
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Chronic subdural hematoma (CSDH) is considered to be an angiogenic disease. Vascular endothelial growth factor (VEGF), one of the important growth factors regulating angiogenesis, is expressed in the neomembranes and also in hematoma fluid, and the Ras/MEK/ERK signaling pathway has been implicated in angiogenesis by VEGF. In the present study, the status of this signaling pathway in CSDH outer membranes was examined using outer membranes obtained during trepanation surgery. ⋯ Ras, Ras-GAP, c-Raf, MEK, ERK and eNOS were detected in all cases. In addition, the expression of p-ERK was confirmed in all cases, and p-ERK was localized to the endothelial cells of the vessels in CSDH outer membranes. These findings indicated that Ras/MEK/ERK signaling is activated in the CSDH outer membranes and suggested the possibility that the Ras/MEK/ERK pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDHs.
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Ghrelin has been shown to be anti-inflammatory and neuroprotective in models of neurologic injury. We hypothesize that treatment with ghrelin will attenuate breakdown of the blood brain barrier (BBB) and apoptosis 24h following traumatic brain injury (TBI). We believe this protection is at least in part mediated by up-regulation of UCP-2, thereby stabilizing mitochondria and preventing up-regulation of caspase-3. ⋯ Treatment with ghrelin significantly increased UCP-2 compared to TBI alone and this increase in UCP-2 expression was associated with a decrease in expression of caspase-3. Early ghrelin treatment prevents TBI induced BBB disruption and TBI mediated apoptosis 24h following injury. These results demonstrate the neuroprotective potential of ghrelin as a therapy in TBI.
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Post-ischemic hyperglycemia may be one of the triggers of ischemic neuronal damage. However, the detailed mechanisms of this injury process are still unknown. Here, we focused on the involvement of the sodium-glucose transporter (SGLT), which transports glucose together with Na(+) ions, and generates inward currents while transporting glucose into cells, resulting in depolarization and increased excitability. ⋯ In contrast, phlorizin (10 or 40μg/mouse, i.c.v.) significantly and dose-dependently suppressed ischemic neuronal damage without reducing the elevation of FBG. Moreover, the development of neuronal damage was significantly and dose-dependently exacerbated following i.c.v. administration of glucose (10% or 25% (w/v)), and its exacerbation was suppressed by i.c.v. administration of phlorizin (40μg/mouse). These results suggest that cerebral SGLT is activated by post-ischemic hyperglycemia and may be involved in the exacerbation of ischemic neuronal damage.