Brain research
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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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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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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.
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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.
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Mammals express ∼20 different connexins, the main gap junction forming proteins in mammals, and 3 pannexins, homologs of innexins, the main gap junction forming proteins in invertebrates. In both classes of gap junction, each channel is formed by two hemichannels, one contributed by each of the coupled cells. There is now general, if not universal, agreement that hemichannels of both classes can open in response to various physiological and pathological stimuli when they are not apposed to another hemichannels and face the external milieu. ⋯ Astrocytes release ATP and glutamate which can kill neurons in co-culture through activation of neuronal pannexin hemichannels. These studies implicate two kinds of gap junction hemichannel in inflammatory responses and cell death. This article is part of a Special Issue entitled Electrical Synapses.