Brain research
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Inflammatory and oxidative damage play a pivotal role in cerebral ischemic pathogenesis and may represent a therapeutic target. Octreotide (OCT) has been proved to elicit a variety of biological effects through its anti-inflammatory and anti-oxidant properties in the treatment of severe acute pancreatitis and ischemia-reperfusion injury in retina and intestine. However little is known regarding the effect of OCT in ischemic stroke. Here, we designed this study to investigate the protective effect of OCT in ischemic stroke and explore the potential underlying mechanisms. ⋯ OCT protected the brain against cerebral ischemic damage; this effect may be through upregulation of transcription factor Nrf2, HO-1 and downregulation of NF-κB expression.
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In this study, we investigated the therapeutic effects of treatment with (R)-Se-phenyl thiazolidine-4-carboselenoate (Se-PTC), an organic selenium compound with antinociceptive properties, against mechanical and thermal hyperalgesia induced by brachial plexus avulsion (BPA), a neuropathic model in mice. The involvement of cannabinoid CB(1) and CB(2) receptors in the Se-PTC anti-hyperalgesic effect was also investigated. Se-PTC treatment at (25 and 50mg/kg, per oral, p.o.) lowered (BPA model) induced mechanical and thermal hyperalgesia in mice. ⋯ The results suggest that the mechanical and thermal hyperalgesia observed following BPA in mice is dependent on cannabinoid receptors. The results indicate that modulating cannabinoid receptors represent a valuable approach for the treatment of neuropathic pain. In conclusion, the results suggested that Se-PTC produces pronounced mechanical and thermal anti-hyperalgesic effects in neuropathic models in mice by modulating CB(1) and CB(2) receptors.
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Although the risk factor for harboring the apolipoprotein E4 (apoE4) allele in late-onset Alzheimer's disease (AD) is well known, the mechanism by which apoE4 contributes to AD pathogenesis has yet to be clarified. Preferential cleavage of the ApoE4 isoform relative to other polymorphic forms appears to be significant, as the resulting fragments are associated with hallmarks of AD. To examine the possible role of apoE4 proteolysis in AD, we designed a site-directed antibody directed at position D172, which would yield a predicted amino-terminal fragment previously identified in AD brain extracts. ⋯ Mass spectrometry confirmed the identity of this 18kDa fragment as being an amino-terminal fragment of apoE4. Immunohistochemical experiments indicated the nApoE4CF Ab specifically labeled neurofibrillary tangles (NFTs) in AD frontal cortex sections that colocalized with the mature tangle marker PHF-1. Taken together, these results suggest a novel cleavage event of apoE4, generating an amino-terminal fragment that localizes within NFTs of the AD brain.
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The Na(+)/H(+) exchanger (NHE) is involved in the regulation of intracellular pH and volume by mediating the electroneutral transport of H(+) against an influx of Na(+) ions. Since NHE1 regulates pH in neurons and astrocytes and it is expressed in nociceptive nerve fibers, it is likely that NHE may modulate neuronal excitability and pain transmission. The purpose of this study was to assess the participation of peripheral and spinal NHE in the secondary allodynia/hyperalgesia induced by formalin. ⋯ In addition, formalin diminished NHE1 protein expression in DRG at day 12. These results suggest that NHE1 plays a role in pain processing at peripheral and spinal levels in formalin-induced long-lasting nociceptive behaviors. Additionally, these results suggest that proteins involved in pH regulation could be targets for the development of new analgesic drugs.
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It has been proved that pre-treatment with leonurine could protect brain tissue against ischemic injury by exerting antioxidant effects and regulating mitochondrial function. Whether this protective effect applies to acute phase after cerebral ischemia, we therefore investigate the potential neuroprotective role of leonurine and the underlying mechanisms in cerebral ischemia. ⋯ The results showed that leonurine protected brain injury by increased activities of UCP4, SOD, CAT and Bcl-2, decreased levels of MDA and Bax, and ameliorated ultrastructure of mitochondria in experimental stroke.