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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Traumatic axonal injury (TAI), a feature of traumatic brain injury (TBI), progressively evolves over hours through impaired axonal transport and is thought to be a major contributor to cognitive dysfunction. In spite of various studies suggesting that pharmacologic or physiologic interventions might reduce TAI, clinical neuroprotective treatments are still unavailable. Edaravone, a free radical scavenger, has been shown to exert neuroprotective effects in animal models of several brain disorders. ⋯ With treatment 1h after impact, axonal injury was also significantly suppressed and this therapeutic effect persisted up to 6h after impact. Furthermore, behavioral tests performed 9 days after injury showed memory deficits in saline-treated traumatized mice, which were not evident in the edaravone-treated group. These results suggest that edaravone protects against memory deficits following TBI and that this protection is mediated by suppression of TAI and oxidative stress.
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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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Transcranial direct current stimulation (tDCS) has been suggested as a therapeutic tool for pain syndromes. Although initial results in human subjects are encouraging, it still remains unclear whether the effects of tDCS can reverse maladaptive plasticity associated with chronic pain. To investigate this question, we tested whether tDCS can reverse the specific behavioral effects of chronic stress in the pain system, and also those indexed by corticosterone and interleukin-1β levels in serum and TNFα levels in the hippocampus, in a well-controlled rat model of chronic restraint stress (CRS). ⋯ This model of CRS proved effective to induce chronic pain, as the animals exhibited hyperalgesia and mechanical allodynia. The hot plate test showed an analgesic effect, and the von Frey test, an anti-allodynic effect after the last tDCS session, and there was a significant decrease in hippocampal TNFα levels. These results support the notion that tDCS reverses the detrimental effects of chronic stress on the pain system and decreases TNFα levels in the hippocampus.