Neuropharmacology
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Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of beta amyloid (Aβ) and neuronal loss particularly in the hippocampus. Accumulating evidences have implied that insulin signaling impairment plays a key role in the pathology of AD; as much as it is considered as type 3 Diabetes. MAPKs are a group of signaling molecules which are involved in pathobiology of AD. ⋯ The results showed that insulin in 6 but not 0.5 mU reversed the memory loss induced by Aβ25-35. Western blot analysis revealed that Aβ25-35 induced elevation of caspase-3 and all 3 MAPks subfamily activity, while insulin in 6 mu restored ERK and P38 activation but has no effect on JNK. This study disclosed that intrahippocampal insulin treatment averts not only Aβ-induced memory deterioration but also hippocampal caspase-3, ERK and P38 activation.
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Patients suffering from chronic neuropathic pain are at high risk of co-morbid depression, which burdens healthcare. This work aimed to investigate the effects of resveratrol, a phenolic monomer enriched in red wine and grapes, on pain-related and depressive-like behaviors in mice with mononeuropathy, and explored the mechanism(s). Mice received chronic constriction injury (CCI) of sciatic nerves, and sequentially developed pain-related and depressive-like behaviors, as evidenced by sensory hypersensitivity (thermal hyperalgesia in Hargreaves test and mechanical allodynia in von Frey test) and behavioral despair (prolonged immobility time in forced swim test). ⋯ Furthermore, the antihyperalgesic action of resveratrol was preferentially counteracted by co-administration of the 5-HT7 receptor antagonist SB-258719, while the anti-depression was abrogated by 5-HT1A receptor antagonist WAY-100635. These results confirm that chronic resveratrol administration exerts curative-like effects on thermal hyperalgesia and co-morbid depressive-like behaviors in mice with mononeuropathy. Spinal and supraspinal serotonergic systems (coupled with 5-HT7 and 5-HT1A receptors, respectively) are differentially responsible for the antihyperalgesic and antidepressant-like properties of resveratrol.
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Comparative Study
Urokinase versus Alteplase for intraventricular hemorrhage fibrinolysis.
Intraventricular hemorrhage (IVH) is the most severe form of stroke with intraventricular fibrinolysis (IVF) as a hopeful treatment. Urokinase (uPA) and tissue-type plasminogen activator (tPA) are used for IVF in Human. No clinical trial has evaluated the differential impact of these two fibrinolytics for IVF. ⋯ These results could be explained by the fact that uPA, in contrast of tPA, fails to promote inflammatory processes and neurotoxicity. Our study provides evidence supporting the use of uPA for fibrinolysis of IVH. A clinical trial could be warranted if tPA failed to improve outcomes in human IVH.
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Glycyrrhizin (GL) is a major constituent of licorice root and has been suggested to inhibit the release of high mobility group box-1 (HMGB1), a protein considered representative of damage-associated molecular patterns. We found that GL bound HMGB1 but not RAGE with a moderate equilibrium dissociation constant value based on surface plasmon resonance analysis. This complex formation prevented HMGB1 from binding to RAGE in vitro. ⋯ The expression of TNF-α, IL-1β and IL-6 in injured sites was completely inhibited by GL treatment. In RAGE-/- mice, the effects of GL were not observed. These results suggested that GL may be a novel therapeutic agent for TBI through its interference with HMGB1 and RAGE interaction.
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Thymosin β4 (Tβ4) has many physiological functions that are highly relevant to spinal cord injury (SCI), including neuronal survival, anti-inflammation, wound repair promotion, and angiogenesis. The present study investigated the therapeutic value of Tβ4 in SCI, with a focus on its neuroprotective, anti-inflammatory, and vasculoprotective properties. Tβ4 or a saline control was administered by intraperitoneal injection 30 min, 3 days, or 5 days after SCI with mild compression in rat. ⋯ Tβ4 treatment after SCI was also associated with a significant decrease in pro-inflammatory cytokine gene expression and a significant increase in the mRNA levels of IL-10 compared to the control. Moreover, the size of lesion cavity delineated by astrocyte scar in the injured spinal cord was markedly reduced in Tβ4-treated animals compared to saline-treated controls. Given the known safety of Tβ4 in clinical trials and its beneficial effects on SCI recovery, the results of this study suggested that Tβ4 is a good candidate for SCI treatment in humans.