Molecular neurobiology
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Molecular neurobiology · Aug 2016
Meta AnalysisExogenous Melatonin for Delirium Prevention: a Meta-analysis of Randomized Controlled Trials.
Recently, two high-quality clinical randomized controlled trials (RCTs) regarding the preventive effect of exogenous melatonin on delirium drew inconsistent conclusions. We therefore performed a systemic review to explore whether melatonin had a benefit on delirium prevention. MEDLINE, EMBASE, and Cochrane Library were searched from January 1980 to April 2015 for English language studies. ⋯ No differences were found in the incidence of delirium between the two groups in the elderly patients that were presented to surgical wards. In conclusion, melatonin supplementation had a significant preventive effect in decreasing the incidence of delirium in elderly patients that were presented to medical wards. Further studies should provide sufficient evidence about the effect of melatonin on delirium in a large sample size.
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Molecular neurobiology · Aug 2016
ReviewThe Role of Nitric Oxide and Sympathetic Control in Cerebral Autoregulation in the Setting of Subarachnoid Hemorrhage and Traumatic Brain Injury.
Cerebral autoregulation is defined as the mechanism by which constant cerebral blood flow is maintained despite changes of arterial blood pressure, and arterial blood pressure represents the principle aspect of cerebral autoregulation. The impairment of cerebral autoregulation is reported to be involved in several diseases. However, the concept, mechanisms, and pathological dysfunction of cerebral autoregulation are beyond full comprehension. ⋯ Additionally, impaired cerebral autoregulation following subarachnoid hemorrhage and traumatic brain injury has been proven by several descriptive studies, although without corresponding explanations. As the most important mechanisms of cerebral autoregulation, the changes of nitric oxide and sympathetic stimulation play significant roles in these insults. Therefore, the in-depth researches of nitric oxide and sympathetic nerve in cerebral autoregulation may help to develop new therapeutic targets.
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Molecular neurobiology · Aug 2016
The Association of Palmitoylethanolamide with Luteolin Decreases Autophagy in Spinal Cord Injury.
Spinal cord injury (SCI) is a devastating condition of the central nervous system (CNS) often resulting in severe functional impairment and for which there are not yet restorative therapies. In the present study, we performed a widely used model of SCI to determine the neuroprotective propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a flavonoid luteolin (Lut), given as a co-ultramicronized compound co-ultraPEALut. In particular, by western blot analysis and immunofluorescence staining, we investigated whether this compound (at the dose of 1 mg/kg) was able to modulate autophagy. ⋯ In contrast, this compound decreased the levels of mammalian target of rapamycin (mTOR), p-Akt, and p-70S6K which are proteins that inhibit autophagy. These data confirmed that the protective role of co-ultraPEALut is associated with inhibition of excessive autophagy and regulation of protein degradation. Therefore, treatment with co-ultraPEALut could be considered as a possible therapeutic approach in an acute traumatic lesion like SCI.
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Molecular neurobiology · Aug 2016
Interleukin-17A Acts to Maintain Neuropathic Pain Through Activation of CaMKII/CREB Signaling in Spinal Neurons.
Immunity and neuroinflammation play major roles in neuropathic pain. Spinal interleukin (IL)-17A, as a mediator connecting innate and adaptive immunity, has been shown to be an important cytokine in neuroinflammation and acute neuropathic pain. However, the effects and underlying mechanisms of spinal IL-17A in the maintenance of neuropathic pain remain unknown. ⋯ Furthermore, we showed that blocking CaMKII with KN93 significantly reduced SNL- or rIL-17A-induced hyperalgesia and p-CREB expression. Our in vitro data showed that KN93 also significantly inhibited rIL-17A-induced CREB activation in primary cultured spinal neurons. Taken together, our study indicates that astrocytic IL-17A plays important roles in the maintenance of neuropathic pain through CaMKII/CREB signaling pathway in spinal cord, and thus targeting IL-17A may offer an attractive strategy for the treatment of chronic persistent neuropathic pain.
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Molecular neurobiology · Aug 2016
BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome.
Brain-derived neurotrophic factor (BDNF) promotes synaptic strengthening through the regulation of kinase and phosphatase activity. Conversely, striatal-enriched protein tyrosine phosphatase (STEP) opposes synaptic strengthening through inactivation or internalization of signaling molecules. Here, we investigated whether BDNF regulates STEP levels/activity. ⋯ BDNF also promoted UPS-mediated STEP61 degradation in cultured striatal and hippocampal neurons. In contrast, nerve growth factor and neurotrophin-3 had no effect on STEP61 levels. Our results thus indicate that STEP61 degradation is an important event in BDNF-mediated effects.