Neuropharmacology
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Galantamine is a drug currently used to treat Alzheimer's disease (AD); in this group of patients it has been observed that concomitant ischemic brain injury can accelerate their cognitive deficit. We have previously shown that galantamine can afford neuroprotection on in vitro and in vivo models related to brain ischemia. In this context, this study was planned to investigate the intracellular signaling pathways implicated in the protective effect of galantamine on an in vitro brain ischemia-reperfusion model, namely rat hippocampal slices subjected to oxygen and glucose deprivation (OGD) followed by reoxygenation. ⋯ ROS production by NADPH oxidase (NOX) activation was also inhibited by galantamine. In conclusion, galantamine afforded neuroprotection under OGD-reoxygenation conditions by activating a signaling pathway that involves nicotinic receptors, Jak2 and the consequent inhibition of NOX and NFκB/iNOS. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
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Subjective tinnitus is a chronic neurological disorder in which phantom sounds are perceived. Drugs that increase GABAergic neurotransmission in the CNS are sometimes used as a treatment. One such drug is the GABA(B) receptor agonist L-baclofen. ⋯ Following washout from the 3 mg/kg dose, but not the 5 mg/kg dose, the significant decrease in the SR for the acoustic trauma group returned, suggesting a return of the tinnitus. These results suggest that L-baclofen should be reconsidered as a drug treatment for tinnitus. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
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It has been demonstrated that opioid and cannabinoid receptor systems can produce similar signal transduction and behavioural effects. Neuropeptide FF (NPFF) belongs to an opioid-modulating peptide family. NPFF has been reported to play important roles in control of pain and analgesia through interactions with the opioid system. ⋯ These data provide the first evidence for a functional interaction between NPFF and cannabinoid systems, indicating that activation of central NPFF receptors interferes with cannabinoid-mediated central and peripheral antinociception. Intriguingly, the present work may pave the way for a new strategy of using combination treatment of cannabinoid and NPFF agonists for pain management. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
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Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic stroke. MFG-E8 is a 66-kDa glycoprotein that has shown tissue protection in various models of organ injury. However, the potential role of MFG-E8 in cerebral ischemia has not been investigated. ⋯ Measures associated with improved outcome included reduced microglial inflammatory cytokine secretion, adhesion molecules and neutrophil influx, cleaved caspase-3, and upregulation of peroxisome proliferator activated receptor-γ (PPAR-γ), and Bcl-2/Bax ratio leading to decreased apoptosis. Thus, rhMFG-E8 treatment is neuroprotective against cerebral ischemia through suppression of inflammation and apoptosis. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
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Curcumin, a phenolic compound present in Curcuma longa, has been reported to exert antinociceptive effects in some animal models, but the mechanisms remain to be elucidated. This work aimed to investigate the antinociceptive action of curcumin on neuropathic pain and the underlying mechanism(s). Chronic constriction injury (CCI), a canonical animal model of neuropathic pain, was produced by loosely ligating the sciatic nerve in mice and von Frey hair or hot plate test was used to assess mechanical allodynia or thermal hyperalgesia (to heat), respectively. ⋯ Collectively, these findings indicate that the descending monoamine system (coupled with spinal β(2)-adrenoceptor and 5-HT(1A) receptor) is critical for the modality-specific antinociceptive effect of curcumin in neuropathic pain. Delta- and mu-opioid receptors are likely rendered as downstream targets, accordingly. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.