Life sciences
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The aim of the present study was to evaluate the antinociceptive effect of the novel pyrazoline methyl ester: 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4). ⋯ The results of the present study suggest that MPF4 represents a potential target for the development of new drugs to treat persistent inflammatory pain.
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Agitation and aggression are common behavioral sequelae of traumatic brain injury (TBI). The management of these symptoms is critical for effective patient care and therefore antipsychotics are routinely administered even though the benefits vs. risks of this approach on functional outcome after TBI are unclear. A recent study from our group revealed that both haloperidol and risperidone impaired recovery when administered prior to testing. However, the results may have been confounded by drug-induced sedation. Hence, the current study reevaluated the behavioral effects of haloperidol and risperidone when provided after daily testing, thus circumventing the potential sedative effect. ⋯ These data support our previous finding that chronic haloperidol and risperidone hinder the recovery of TBI-induced deficits, and augment those data by demonstrating that the effects are not mediated by drug-induced sedation.
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Acupuncture has been used in clinical trials for the treatment of abdominal pain in patients with irritable bowel syndrome (IBS). However, scientific evidence is still lacking and the underlying mechanism remains largely unexplored. The aim of this study was to examine the effects of repeated administration of electro-acupuncture (EA) on chronic visceral hypersensitivity and on the phosphorylation of spinal cord N-methyl-D-aspartic acid (NMDA) receptors in a rat model of IBS. ⋯ Furthermore, rats with chronic visceral hypersensitivity exhibited high-level expression of phosphorylated NMDA receptor subunit 1 (pNR1) in the spinal cord (L4-L5 segments), which was markedly attenuated by EA treatment. In addition, EA at ST-36 and ST-37 neither altered the pain threshold of normal rats nor affected the expression of pNR1 in the lumbosacral spinal cord. Altogether, these data indicate that the EA-mediated attenuation of chronic visceral hypersensitivity is correlated with the down-regulation of NMDA receptors phosphorylation at the spinal level.
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Diabetes-induced learning and memory impairment, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involve direct neuronal damage caused by intracellular glucose. The present study was designed to investigate the effect of lycopene, a potent anti-oxidant and anti-inflammatory molecule, on cognitive functions, oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. Cognitive functions were investigated using a spatial version of the Morris water maze test. ⋯ Serum tumor necrosis factor-alpha, an inflammatory marker, was found to increase by 8 fold in diabetic rats. Chronic treatment with lycopene (1, 2 and 4 mg/kg; p.o.) significantly and dose dependently attenuated cognitive deficit, increased acetylcholinesterase activity, oxidative-nitrosative stress and inflammation in diabetic rats. The results emphasize the involvement of oxidative-nitrosative stress and peripheral inflammation in the development of cognitive impairment in diabetic animals and point towards the therapeutic potential of lycopene in diabetes-induced learning and memory impairment.
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We have shown previously, that the most neurotoxic factor from activated microglia is glutamate that is produced by glutaminase utilizing extracellular glutamine as a substrate. Drugs that inhibit glutaminase or gap junction through which the glutamate is released were effective in reducing neurotoxic activity of microglia. In this study, to elucidate whether or not a similar mechanism is operating in macrophages infiltrating into the central nervous system during inflammatory, demyelinating, and ischemic brain diseases, we examined the neurotoxicity induced by macrophages, in comparison with microglia in vitro. ⋯ These results revealed that macrophages produce glutamate via glutaminase from extracelluar glutamine, and release it through gap junctions. This study demonstrated that a similar machinery is operating in macrophages as well, and DON and CBX that prevent microglia-mediated neurotoxicity should be effective for preventing macrophage-mediated neurotoxicity. Thus, these drugs may be effective therapeutic reagents for inflammatory, demyelinating, and ischemic brain diseases.