Resveratrol administration after adverse circulatory conditions is known to be protective, however, the mechanism by which resveratrol produces the salutary effects remains unknown. Recently, it was shown that resveratrol activates estrogen receptor (ER) in endothelial cells. We hypothesized that resveratrol administration in males after trauma-hemorrhage decreases cytokine production and protects against hepatic injury through an ER-dependent pathway. To study this, male Sprague-Dawley rats were subjected to trauma-hemorrhage (mean blood pressure, 40 mmHg for 90 min) then resuscitation. A single dose of resveratrol (30 mg/kg of body weight) with or without an ER antagonist (ICI 182,780), ICI 182,780, or vehicle was administered i.v. during resuscitation. Tissue myeloperoxidase activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant 1 (CINC-1), CINC-3, intercellular adhesion molecule 1, and interleukin 6 (IL-6) levels in the liver and plasma aspartate aminotransferase and alanine aminotransferase concentrations were measured at 2 and 24 h postresuscitation (n = 6 rats per group). One-way ANOVA and Tukey test were used for statistical analysis. Results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, CINC-1, CINC-3, intercellular adhesion molecule 1, and IL-6 levels and plasma aspartate aminotransferase and alanine aminotransferase concentrations. These parameters were significantly improved in the resveratrol-treated rats at both 2 and 24 h postresuscitation. Coadministration of the ER antagonist ICI 182,780 prevented the beneficial effects of resveratrol administration on postresuscitation proinflammatory responses and hepatic injury. Thus, resveratrol administration after trauma-hemorrhage attenuated hepatic injury, likely through reduction of proinflammatory mediators. Resveratrol-mediated hepatic preservation seemed to progress via an ER-related pathway.

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Pretreatment with small-dose ketamine 0.2 mg/kg provides a simple and safe means of reducing the incidence of withdrawal movements induced by the injection of rocuronium, a short-acting nondepolarizing muscle relaxant.

This study investigated the expression of nitric oxide (NO)-synthesizing enzymes and the glial reaction in the rat hippocampal formation following sleep deprivation for 5 days. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity was markedly reduced in the hippocampal CA1, CA2 and CA3 sectors as well as in the dentate gyrus, suggesting a suppression of NO production in these areas. Microglial cells were hypertrophic and showed an up-regulation of complement type 3 receptors as determined by antibody OX-42. However, expression of major histocompatibility complex class I and II antigens, and antigen of monocyte/macrophage lineage marked by OX-18, OX-6 and ED1, respectively, was undetected. Astrocytes also displayed hypertrophied processes with enhanced glial fibrillary acidic protein (GFAP) immunoreactivity. Western blots of hippocampal tissues corroborated the above-mentioned morphological findings in that expression of NO-synthase (NOS) was decreased while that of OX-42 and GFAP was increased in the sleep-deprived rats. Since NO is thought to be involved in memory consolidation processes in the hippocampus during sleep, the inhibition of NADPH-d and NOS reactivities may account for the memory decline after long-term sleep deprivation. The concomitant reactions in microglia and astrocytes suggest the involvement of these cells in the deleterious effect of prolonged sleep deprivation.

Alzheimer's disease (AD) is associated with neurodegenerative changes resulting clinically in progressive cognitive and functional deficits. The only therapies are the cholinesterase inhibitors donepezil, galantamine and rivastigmine and the N-methyl-D-aspartate-receptor antagonist memantine. Donepezil acts primarily on the cholinergic system as a symptomatic treatment, but it also has potential for disease modification and may reduce the rate of progression of AD. This review explores the potential for disease modifying effects of donepezil. Several neuroprotective mechanisms that are independent of cholinesterase inhibition, are suggested. Donepezil has demonstrated a range of effects, including protecting against amyloid β, ischaemia and glutamate toxicity; slowing of progression of hippocampal atrophy; and up-regulation of nicotinic acetylcholine receptors. Clinically, early and continuous treatment with donepezil is considered to preserve cognitive function more effectively than delayed treatment. The possible neuroprotective effects of donepezil and the potential for disease pathway modification highlight the importance of early diagnosis and treatment initiation in AD.